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1. Chinese Expert Consensus on Medication Safety in Polypharmacy in Type 2 Diabetics with Chronic Kidney Disease
Chinese Medical Association Clinical Pharmacy Branch
Chinese General Practice    2022, 25 (23): 2819-2835.   DOI: 10.12114/j.issn.1007-9572.2022.01.304
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Diabetes is a serious public health problem worldwide. The prevalence of chronic kidney disease (CKD) secondary to type 2 diabetes mellitus (T2DM) is growing with the increase of T2DM prevalence. There is no comprehensive guideline on medication safety in polypharmacy in patients with T2DM-related CKD. This consensus provides guidance on safety issues in polypharmacy for clinical pharmacists and Chinese patients with T2DM-related CKD, and a summary of the information on usage and dosage, and related pharmaceutical characteristics of drugs as well as medication for special populations for supporting clinical medical workers in delivering standardized medication services.

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2. Analysis of Therapeutic Effects of Probiotics on Renal Injury Induced by Hyperuricemia 
XIAO Yuanxun,ZHANG Congxin,ZENG Xianli,YUAN Zhichao
Chinese General Practice    2020, 23 (11): 1376-1382.   DOI: 10.12114/j.issn.1007-9572.2019.00.479
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Background The treatment of hyperuricemia with allopurinol is considered to be clinically effective.However,the treatment of renal injury caused by hyperuricemia with allopurinol is still controversial.Most scholars believe that allopurinol can effectively protect the kidney,but its use was limited due to the possible side effects of renal injury.Currently,probiotics have been shown to effectively degrade uric acid(UA).Objective Probiotics were screened from traditional pickles to analyze their effects on hyperuricemia with renal injury.Methods From December 2017 to August 2018,lactic acid bacteria(LAB) were isolated from 18 kinds of pickles collected from different provinces.Firstly,functional LAB with good adhesion,which could degrade nucleosides and were resistant to acid,bile salts,trypsin and pepsin,were selected by microscopic examination after hydrogen peroxide(H2O2) and HE staining.The strains were identified by 16SrDNA sequence analysis and finally applied to the renal injury model of hyperuricemia.A total of 40 rats were divided into normal group(n=10),model group(n=10),S12 strain intervention group(n=10) and allopurinol intervention group(n=10) by random number table method.Levels of UA,serum creatinine(Scr) and urea nitrogen(BUN) were measured on days 0,10 and 20.Results Fourteen strains of LAB were isolated from 18 kinds of pickles,among which S1,S5,S12 and S14 were used as candidate strains.The purity of S12 strain was the highest,so it was used for animal test.At day 10,Scr level in four groups showed no significantly difference(P>0.05),while the levels of UA and BUN in four groups were significantly different(P<0.05).UA and BUN levels in the model group,S12 strain intervention group and allopurinol intervention group were higher than those in the normal group(P<0.05).On the day 20,there were significant differences in the levels of UA,Scr and BUN in four groups(P<0.05);among them,UA,Scr and BUN levels in the model group,S12 strain intervention group,and allopurinol intervention group were higher than those in the normal group;UA,Scr and BUN levels in the S12 strain intervention group were lower than those in the model group;UA and BUN levels in allopurinol intervention group were lower than those in the model group,while BUN level in allopurinol intervention group was higher than that in the S12 strain intervention group(P<0.05).Conclusion Probiotics have a certain degree of protective and therapeutic effects on hyperuricemia with renal injury.
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3. Recent Advances in Chinese and Western Medicine Treatments for Diabetic Kidney Disease
Ying WANG, Jingwei ZHOU, Zhen WANG, Yingxia YANG, Yaoxian WANG
Chinese General Practice    2022, 25 (12): 1411-1417.   DOI: 10.12114/j.issn.1007-9572.2021.02.117
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Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease in China, which greatly negatively impacts public health and patients' quality of life. Recently, multiple guidelines have updated their recommendations to optimize the treatment and management of individuals with DKD. New antihyperglycemic drugs offer new options for DKD. Traditional Chinese medicine (TCM) has a long history in treating DKD, and relevant theories have been continuously enriched and developed. Along with the increasing application of evidence-based medicine in TCM research, the benefits of TCM treatments in DKD have been gradually recognized and valued, such as relieving fatigue, edema, backache and other symptoms, lowering protein in the urine, protecting kidney function, enhancing treatment efficiency, reducing the risk of end-stage renal disease, and improving the long-term prognosis. This article gave a summary and strengths analysis of the latest advances in TCM and Western medicine treatments for DKD.

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4. Clinical Practice Guideline for Chinese Medicine in the Treatment of Idiopathic Membranous Nephropathy (2021)
Nephrology Branch of China Association of Chinese Medicine, Nephrology Committee of Guangdong Provincial Association of Chinese Medicine, YANG Lihong, SU Peiling, BAO Kun
Chinese General Practice    2023, 26 (06): 647-659.   DOI: 10.12114/j.issn.1007-9572.2022.0758
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In China, idiopathic membranous nephropathy (IMN) accounts for 24.9% of glomerular diseases, the second highest share, and is increasing year by year. Chinese medicine has been widely used in the clinical practice of IMN. However, there are no evidence-based practice guidelines for the treatment of IMN with Chinese medicine. This guideline followed the methods and steps of the guideline development manual. The level of the body of the evidence was assessed by the GRADE. An outline of the clinical questions was formulated through interviews with leading Chinese medicine experts and a review of relevant clinical guidelines. Based on the results of a systematic review of authoritative textbooks and clinical research literature, a clinical question list, a clinical outcome assessment index for IMN, and a list of types of Chinese medicine syndromes were developed, and a national expert survey was conducted to identify the clinical questions included in this guideline. A consensus meeting was held to finalize 10 recommendations for treating IMN with Chinese medicine. This guideline focuses on the clinical practice of Chinese medicine in the treatment of IMN, and is applicable to all levels of Chinese medicine and integrated Chinese and Western medicine institutions, as well as medical institutions and healthcare workers who provide Chinese medicine services.

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5. Rosuvastatin Calcium with Metformin Improves Kidney Function in a Rat Model of Diabetes by Regulating the Expression of Glucose Transporter 4
Gechu SHANG, Xiaoyong WANG, Yan GAO
Chinese General Practice    2022, 25 (18): 2291-2296.   DOI: 10.12114/j.issn.1007-9572.2022.0039
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Background

Rosuvastatin calcium with metformin improves diabetic renal injury, but the mechanism is not yet fully understood.

Objective

To explore the mechanism of action of rosuvastatin calcium with metformin improving renal injury in a rat model of streptozotocin (STZ) -induced type 2 diabetes mellitus (T2DM) .

Methods

Forty clean grade Wistar rats were equally randomized into a control group (group C) , a metformin group (group M) , a metformin+low-dose rosuvastatin calcium group (group M+RL) , and a metformin+high-dose rosuvastatin calcium group (group M+RH) from July to October 2021. T2DM model was established for three groups (except for group C) using intraperitoneal injection of STZ. Then drug was administered by intragastric administration to the groups as follows: equal amount of 0.9% sodium chloride solution for group C, metformin (200 mg·kg-1·d-1) for group M, metformin (200 mg·kg-1·d-1) suspension+rosuvastatin calcium (0.42 mg·kg-1·d-1) for group M+RL, and metformin (200 mg·kg-1·d-1) suspension+rosuvastatin calcium (0.83 mg·kg-1·d-1) for group M+RH. Rats were sacrificed after 6 weeks of intervention, while their blood and kidney tissues were collected. The extent of injury of kidney tissues was observed under light microscope after being stained with H&E, and was analyzed using Image-Pro Plus 6.0 after being stained with periodic-acid schiff, and Masson's trichrome, respectively. The expression of glucose transporter 4 (GLUT4) mRNA in the renal tissue was measured by real-time polymerase chain reaction (PCR) , and the protein levels of GLUT4 were detected by Western-blotting.

Results

Compared with group C, the glomerulus of rats in other three groups showed significant structural damage, accompanied by inflammatory cell infiltration and interstitial fibrosis. Moreover, mRNA expression levels of GLUT4 in these groups were significantly lowered (P<0.05) . Furthermore, the protein levels of GLUT4 in groups M and M+RL were lowered notably (P<0.05) . The mRNA and protein expression levels of GLUT4 in group M+RL or M+RH were higher than those of group M (P<0.05) . In addition, the mRNA and protein expression levels of GLUT4 in M+RH group were higher than those in M+RL group (P<0.05) .

Conclusion

Rosuvastatin calcium with metformin could reduce inflammatory cell infiltration in glomerular and tubular, alleviate glomerular basement membrane thickening and tubular vacuolar degeneration, delay the interstitial fibrosis development, and increase GLUT4 mRNA and GLUT4 protein expression in STZ-induced T2DM rats. Moreover, higher dose of rosuvastatin calcium showed better effect. Our study indicated that rosuvastatin calcium combined with metformin may achieve a renoprotective effect by regulating the expression of GLUT4 mRNA and protein in T2DM rats, and this effect may be enhanced with the increase in the dose of rosuvastatin calcium.

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6. Correlation between Atrial Fibrillation and the Risk of New-onset Chronic Kidney Disease in Northern Chinese Population
ZHANG Aili, HOU Qiqi, HAN Quanle, ZHANG Boheng, ZHANG Jiawei, CAO Hongxia, ZHANG Chao, CHEN Shuohua, WU Shouling, LI Kangbo
Chinese General Practice    2023, 26 (36): 4521-4526.   DOI: 10.12114/j.issn.1007-9572.2023.0006
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Background

The global population disease burden report shows that atrial fibrillation (AF) and chronic kidney disease (CKD) have emerged as the fast-growing causes of death in the last 20 years. The concept of cardiorenal syndrome suggests that AF may increase the risk of new-onset CKD, however, there are few studies related to the increased risk of new-onset CKD with AF at home and abroad, and the interaction with age remains unclear atpresent.

Objective

To investigate whether AF increases the risk of new-onset CKD in northern Chinese population.

Methods

The population who attended a comprehensive health check-up for the employees of Kailuan Group in Hebei Province from 2006 to 2010 were selected as study subjects. The general information and laboratory test results of the study subjects were collected, and the study subjects were followed up with the final follow-up date of 2020-12-31 and the end point of new-onset CKD. The included patients were divided into AF group (n=368) and non-AF group (n=110 487) according to the presence or absence of AF. The cumulative incidence of new-onset CKD in patients was calculated using the lifetable method. The Kaplan-Meier method was used to plot the survival curves of the cumulative incidence of new-onset CKD in the AF group and the non-AF group. The Log-rank test was used to compare the differences in the cumulative incidence of CKD between the two groups. The multivariate Cox proportional hazard regression model was used to explore the effect of AF on the risk of new-onset CKD.

Results

AF group was higher than non-AF group in age, male proportion, systolic blood pressure level, diastolic blood pressure level, body mass index, the proportions of education level, participation in physical exercise, hypertension, diabetes, taking hypotensive drugs and hypoglycemic drugs, and high-sensitivity C-reactive protein level (P<0.05) . AF group was lower than non-AF group in the proportion of alcohol consumption, total cholesterol, triacylglycerol and low density lipoprotein cholesterinlevels (P<0.05) . There were statistically significant differences in the incidence and cumulative incidence of new-onset CKD between atrial fibrillation group and non-atrial fibrillation group (P<0.05) . Stratifying the study population by age, there were statistically significant differences in the incidence and cumulative incidence of new-onset CKD in the study subjects aged≤65 years (P<0.05) and statistically significant difference in the incidence of new-onset CKD in the study subjects aged>65 years (P<0.05) . The results of the adjusted multivariate Cox proportional hazard regression analysis showed that AF was a risk factor for new-onset CKD in people aged≤65 years〔HR=1.350, 95%CI (1.038, 1.755) , P=0.025〕.

Conclusion

AF is an independent risk factor for new-onset CKD in northern Chinese population, especially for young and middle-aged populationaged≤65 years.

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7. Interpretation of Diabetes Management in Chronic Kidney Disease: a Consensus Report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO)
YAO Huijuan, YANG Yu, XU Ajing
Chinese General Practice    2023, 26 (12): 1415-1421.   DOI: 10.12114/j.issn.1007-9572.2023.0015
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People with diabetes and chronic kidney disease (CKD) are at high risk for kidney failure, atherosclerotic cardiovascular disease, heart failure, and premature mortality. The American Diabetes Association (ADA) and the Kidney Disease: Improving Global Outcomes (KDIGO) established joint group, and integration of evidence-based recommendations for diabetes management in patients with CKD in accordance with the ADA 2022 standards of medical care in diabetes and KDIGO 2022 Clinical Practice Guideline for Diabetes Management in CKD, and to form the Diabetes Management in Chronic Kidney Disease: a Consensus Report by the ADA and KDIGO. The consensus not only re-emphasizes the published guidelines for screening and diagnosis of CKD, glycemia monitoring, lifestyle therapies, treatment goals, and pharmacologic management, but also specifically emphasizes the importance of comprehensive care in which pharmacotherapy based on a foundation of healthy lifestyle. The consensus states seven core recommendations which provide specific guidance for the use of renin-angiotensin system inhibitors, metformin, sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide 1 receptor agonists, and a nonsteroidal mineral corticoid receptor antagonist. These areas of consensus provide clear direction for implementation of care to improve clinical outcomes of people with diabetes and CKD. Focusing on the main contents of the consensus, we interpreted main recommendations in order to provide concise and practical guidance for clinicians, to achieve the goal of improving the prognosis of patients with diabetes mellitus complicated with CKD.

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8. Interpretation of the KDOQI Clinical Practice Guideline for Nutrition in CKD:2020 Update 
CHENG Gaiping,QIN Wei,LIU Jing,LIU Yuan
Chinese General Practice    2021, 24 (11): 1325-1332.   DOI: 10.12114/j.issn.1007-9572.2021.00.166
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CHENG Gaiping1,QIN Wei2,LIU Jing1,LIU Yuan1*
In September 2020,The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative(KDOQI)updated its clinical practice guideline for nutrition in CKD.Since the publication of the initial KDOQI nutrition guideline 20 years ago,there has been a great accumulation of new evidence about the nutritional management of kidney disease.The guideline was expanded to include patients with end-stage kidney disease or advanced CKD,patients with stages 1-5 CKD without ongoing dialysis and patients with a functional kidney transplant.The updated guideline statements cover 6 primary areas:nutritional assessment,medical nutrition therapy,dietary protein and energy intake,nutritional supplementation,micronutrients,and electrolytes.The guidelines mainly include dietary management rather than all possible nutritional interventions.Focusing on the main contents of the guideline,the paper interpreted main recommendations and discussed the application in light of the actual situation in China.
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9. Effect of Febuxostat on Incidence of Contrast-induced Nephropathy in Patients with Coronary Heart Disease Complicated with Hyperuricemia 
PAN Zhuang,ZHANG Lihua,NIU Shaohui,JIANG Youxu,LI Yuan
Chinese General Practice    2019, 22 (29): 3565-3569.   DOI: 10.12114/j.issn.1007-9572.2019.00.172
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Background The morbidity and mortality of coronary heart disease(CHD) are increasing year by year.More than 1 million people die from CHD every year.Wide application of percutaneous coronary intervention(PCI) for CHD brings about an incidence of contrast-induced nephropathy (CIN) of 2%-30%,which increases the financial burden of patients and society,and affects the prognosis of such patients.Studies have found that there is a close relationship between serum uric acid(sUA) and CIN,and elevated sUA can increase the risk of CIN.Objective To investigate the preventive effect of uric acid lowering therapy on CIN in patients with CHD complicated with hyperuricemia.Methods A total of 100 cases of CHD with hyperuricemia receiving PCI treatment were selected from Department of Cardiovascular,the Second Affiliated Hospital of Zhengzhou University from January 2017 to January 2018,and were randomly and evenly divided into experimental group and control group.Both groups received coronary angiography or coronary stent implantation with secondary prevention therapies for CHD,the difference was that the experimental group took oral febuxostat 40 mg 24 hours and immediately before the surgery,while the control group did not take any drugs for lowering uric acid.Levels of serum creatinine(Scr),sUA and serum cystatin C(Cys-C) measured at 48 hours before surgery and 72 hours after surgery,and the incidence of CIN of both groups were collected and compared.Results The average sUA and Cys-C levels were much lower in the experimental group(P<0.05),while average Scr was similar in both groups at 72 hours after surgery(P>0.05).Compared with baseline,the average Scr and Cys-C levels at 72 hours after surgery changed insignificantly in the experimental group(P>0.05),but average sUA level decreased(P<0.05);in the control group,average Scr and sUA levels had little changes(P>0.05),but Cys-C level increased significantly(P<0.05).The incidence of CIN was 18.0% (9/50) in the experimental group,and 22.0% (11/50) in the control group,showing no significant intergroup difference (χ2=0.250,P=0.617).Multivariate Logistic regression analysis showed that age 〔OR=1.362,95%CI(1.030,1.802) 〕,LDL-C〔OR=1.988,95%CI(1.239,3.190)〕,contrast agent dosage 〔OR=1.426,95%CI(1.097,1.853) 〕,Cys-C at 72 hours after surgery〔OR=3.374,95%CI(2.482,4.581)〕were all factors associated with CIN (P<0.05).Conclusion Although preoperative uric acid lowering treatment could not reduce incidence of CIN,it could inhibit the increase of postoperative Cys-C level.However,its long-term effect on postoperative renal function still needs to be examined by large-scale clinical trials.
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10. Clinicopathological Features of Anticancer Drug-induced Kidney Injury
GENG Tonghui, LI Han, JIN Jingjing, CHENG Meijuan, ZHANG Shenglei, BAI Yaling, XU Jinsheng
Chinese General Practice    2022, 25 (33): 4153-4158.   DOI: 10.12114/j.issn.1007-9572.2022.0372
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Background

The prevalence of anticancer drug-induced kidney injury is increasing, but related renal pathology studies are still rare.

Objective

To analyze the clinicopathological characteristics of patients with anticancer drug-related kidney injury.

Methods

We selected 112 cancer inpatients aged 18 years or older with kidney injury (kidney injury occurred after cancer or nearly at the same time as cancer, and may be directly or indirectly associated with anticancer treatment) detected by kidney biopsy from Department of Nephrology, the Fourth Hospital of Hebei Medical University from October 2013 to August 2021. We assigned those (n=65) who were previously treated with chemotherapy, molecularly targeted drugs or immune checkpoint inhibitors and other systemic treatments to an anticancer drug group, and other cases (n=47) to a non-use anticancer drug group. We collected their demographics, laboratory examination and pathological data, and analyzed the clinical features and pathological characteristics of kidney of those with anticancer drug-related kidney injury.

Results

In the anticancer drug group, acute kidney injury (AKI) occurred in 30 (50.8%) out of 59 cases of solid cancer, and in 4 out of 6 cases of hematological cancer. In non-use anticancer drug group, AKI occurred in 11 (31.4%) out of 35 cases of solid cancer, and in 6 (50.0%) out of 12 cases of hematological cancer. The serum creatinine level increased after treatment in the anticancer drug group (P<0.001) . Anticancer drug group and non-use anticancer drug group had significant differences in sex ratio, smoking prevalence, mean serum albumin and elevated urinary protein excretion prevalence (P<0.05) , but had no significant differences in mean age, hemoglobin, serum creatinine, urea nitrogen, uric acid, D-dimer, total cholesterol, triacylglycerol, and 24-hour urinary protein quantification, as well as prevalence of diabetes, hypertension, and AKI (P>0.05) . Solid cancer patients with anticancer drug treatment had higher prevalence of tubulointerstitial injury (P=0.023) and lower prevalence ofmembranous nephrosis (P=0.004) compared with those without anticancer drug treatment. Renal tubulointerstitial injury was the main pathological manifestations in the anticancer drug group〔34 cases (52.3%) 〕. Membranous nephropathy〔18 cases (38.3%) 〕and tubulointerstitial injury〔18 cases (38.3%) 〕were main pathological manifestations in the non-use anticancer drug group.

Conclusion

There are various clinical and pathological types of anticancer drug-induced kidney injury. The application of anticancer drug may cause damage to renal function, so priority should be given to the prevention of renal tubulointerstitial injury during the treatment.

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11. Advances in the Treatment of Genitourinary Syndrome of Menopause 
LIU Shuangxue, LI Yanhua
Chinese General Practice    2021, 24 (36): 4665-4670.   DOI: 10.12114/j.issn.1007-9572.2021.02.048
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Advances in the Treatment of Genitourinary Syndrome of Menopause
LIU Shuangxue1, LI Yanhua2*
1. Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China
2.Department of General Medicine, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, China
*Corresponding author: LI Yanhua, Chief physician, Master supervisor; E-mail:liyanhua330@163.com
Abstract: Genitourinary syndrome of menopause (GSM) is a symptom that may occur in the vast majority of women, which gradually aggravates with age and time from the menopausal transition, and may seriously affect the daily life and intimacy in marriage in middle-aged and elderly women. However, due to a variety of personal and external factors, the consultation rate of GSM women is low, resulting in a low rate of obtaining effective counseling, appropriate diagnosis and treatment, and lifelong management in this population. We reviewed the advances in the treatment for GSM in peri-menopausal or postmenopausal women, aiming to raise public awareness of GSM and to offer theoretical guidance for related treatment, thereby promoting the physical and mental health of middle-aged and elderly women.
Keywords:Menopause; Female urogenital diseases; Genitourinary syndrome of menopause; Drug therapy; Physical therapy modalities; Early intervention (education)
1. Introduction
Genitourinarysyndromeofmenopause (GSM) refers to the collection of symptoms and signs related to the decrease of estrogen and other sex hormones, involving the changes of the vulva, vagina, urethra, and bladder. The main clinical manifestations include external genitalia, urinary system, and sex, such as vaginal dryness, itching, urinary tract infection, sexual difficulty, and so on[1]. Studies have shown that more than 50% of women develop GSM symptoms at some point in their lives[2]and considering that some people do not see a doctor because of sexual embarrassment or lack of awareness of them, the prevalence of GSM is likely to be underestimated. This paper analyzes the treatment of GSM in peri-menopausal or postmenopausal women, providing a theoretical basis for general practitioners' early intervention, diagnosis and treatment, and health management of GSM, as well as new ideas for specialists to study the disease in the futureto improve the quality of life and happiness of women.
2 Drug therapy
2.1 Menopause Hormone Therapy (MHT)
Menopause Societies at home and abroad have pointed out that the time window of hormone therapy is before the age of 60 or within 10 years after menopause, and its risk depends on the type of drug, dose, time of use, route of administration, start-up time and whether to use progesterone, and the benefits and risks of treatment regimens need to be reassessed regularly[3-4]. Based on some clinical trials and observational studies, this paper summarizes the safety and efficacy of different hormone therapy regimens.
2.1.1 Vaginal estrogen preparation
For GSM symptoms can not be relieved by over-the-counter drug therapy, and there is no indication of systemic hormone therapy, it is recommended to use low-dose vaginal estrogen treatment[3-4]. At present, there are many dosage forms, such as cream, ring, implant, or tablet.
Several clinical trials have confirmed that the use of vaginal estradiol or estriol vaginal preparation (15~50 μg/d) which is much lower than the conventional dose approved by the Food and Drug Administration (FDA) can also significantly reduce vaginal pH and improve sexual function, and there are no adverse reactions[5-7]. The results of the meta-analysis carried out by BIEHL et al.[8] showed that the effective dose of 17 β-estradiol soft capsules (TX-004HR) was as low as 4 μg. The above results support the use of vaginal estrogens with the lowest possible dose to alleviate the symptoms of GSM, and also provide a reference for patients who are concerned aboutthe safety of estrogen exposure or have contraindications for estrogen use.
2.1.2 Systematic MHT
Systemic MHT is recommended for patients with GSM complicated with obvious systemic symptoms. Transdermal and oral administration are two common methods[3-4]. Butthe latest research suggests that lower doses of transdermal estrogen may be a better form of administration, reducing coronary heart disease, stroke, and cardiovascular mortality[10]. In addition, combined estrogen and progesterone therapy (estrogen-progestogen therapy, EPT) is recommended forwomen with uteri[3], and the E3N cohort study found that compared with synthetic progesterone, micronized progesterone had a lower effect on breast proliferation and did not increase the prevalence of breast cancer[11]. Women with a hysterectomy can be treated with estrogen alone[3-4]. Furthermore, in a previous clinical controlled study, GENG et al.[12] demonstrated that MHT could reshape the composition of vaginal microorganisms and significantly increase the abundance of lactic acid bacteria, which was of great significance for the clinical treatment of GSM.
2.1.3 Compound hormone
At present, there is a bioequivalent compound hormone therapy, which can combine a variety of hormones (such as estradiol, estriol, dehydroepiandrosterone, progesterone, etc.), but clinicians consider using compound hormone only if the patient is allergic or unable to tolerate the treatment approved by FDA. There is evidence that compound hormones can increase the prevalence of endometrial cancer[13]. Therefore, there are some safety problems in compound hormone therapy, and further research is still needed.
2.2 Tissue-selective estrogen complex
The tissue-selective estrogen complex is composed of conjugated equine estrogens (CEE) and selective estrogen receptor modulator Bazedoxifene (BZA) and does not contain progesterone. A 12-week multicenter clinical trial of CEE/BZA in postmenopausal women with one or more moderate to severe vulvovaginal atrophy (VVA) symptoms, and vaginal pH > 5.0 found that CEE/BZA significantly improved vaginal cytology, decreased vaginal pH, and effectively relieved VVA symptoms[14]. In addition, according to the analysis of this trial data, several studies have shown that there is an approximately linear relationship between VVA symptoms and sexual function so that CEE/BZA can significantly improve sexual function while relieving VVA symptoms[15], and there is no significant difference in efficacy and safety among different ethnic groups[16]. Therefore, women who cannot tolerate adverse reactions to progesterone can benefit from the combination of CEE/BZA.
2.3 Selective estrogen receptor modulator (SERM)
SERMsare tissue-specific and can showexcitatory or antagonistic effects. Currently, ospemifene has been approved by the FDA and the European Medicines Agency for the treatment of postmenopausal women with moderate to severe sexual dysfunction caused by GSM or with VVA symptoms but not suitable for local hormone therapy[17]. Pharmacodynamics showed that
ospemifene had an estrogenic effect on the vaginal epithelium, significantly improved the morphology of vaginal mucosa, relieved dyspareunia[18], and could prevent postmenopausal urinary tract infection[19]. It may also be a potential treatment for VVA complicated with overactive bladder[20] and did not produce an estrogenic effect in breast tissue, and the stimulating effect on endometrium was neutral or minimal[18]. It has good tolerance and safety. However, it is still necessary to conduct long-term randomized controlled trials with large samples, including high-risk patients, in order to better clarify the safety of ospemifene.
2.4 Intravaginal dehydroepiandrosterone
According to the mechanism of human endocrinology, dehydroepiandrosterone (DHEA) produced by the adrenal gland is the only source of sex hormones in postmenopausal women[21]. At present, intravaginal DHEA (prasterone, 6.5mg/d) has been approved by FDA for the treatment of moderate to severe dyspareunia due to GSM[22]. A phase Ⅲclinical trial showed that daily intravaginal administration of DHEA for 12 weeks significantly reduced vaginal pH, improved vaginal cytology, and alleviated vaginal dryness and dyspareunia[23]. And SAUER et al.[24] analyzed that the curative effect of DHEA was similar to that of vaginal estrogen preparations. In addition, because DHEA transformation is cell-specific and tissue-specific and does not cause significant changes in serum hormone levels[21], it can be speculated that its potential risk is relatively smaller than that of local estrogen preparations. According to statistics, only 6% of women reported one adverse reaction reasonably related to treatment, vaginal discharge, which was caused by the melting of drugs at body temperature[23], indicating that this treatment has a high benefit-risk ratio.
2.5 Intravaginal oxytocin gel
GHORBANI et al.[25] pointed out that intravaginal oxytocin gel can improve vaginal cytology and subjective symptoms, and does not significantly change the thickness of the endometriumin the latest meta-analysis. The main mechanism of intravaginal oxytocin gel is that oxytocin stimulates vaginal cell proliferation in a time-and dose-dependent manner[26]. But its long-term effectiveness and safety remain to be verified.
2.6 Vaginal lubricants and moisturizers
The North American Menopause Societyrecommends vaginal lubricants and moisturizers as first-line therapy for GSM to reduce daily discomfort and improve sexual comfort[9]. Some studies have found that some common vaginal lubricants and moisturizers can inhibit the growth of pathogenic Escherichia coli while having a weak inhibitory effect on the growth of potential protective Lactobacillus crispatus[27]. This mechanism may improve vaginal health to some extent.
In addition, a study has found that hyperosmolar lubricantshave cytotoxic effects on vaginal epithelial cells, induce abnormal secretion of inflammatory mediators and destroy barriers[28]. Therefore, Potter et al.[29] have clearly proposed that when using vaginal lubricants and moisturizers, products with pH (about 3.5, range 3 ~ 5) and osmotic pressure (about 380 mOsmol/kg, range 200 ~ 600 mOsmol/kg) as close as possible to vaginal secretion should be selected to reduce endothelial stimulation and adverse reactions, and products should not contain paraben, chlorhexidine, and polyquaternium-15. Because such preservatives may cause vaginal flora imbalance.
2.7 Phytoestrogens (PEs)
PEsare compounds with estrogenic activity, which can be derived from soy, Pueraria mirifica, flaxseed, fennel, and other plants. They can be divided into three classes: isoflavones, lignans,
andcoumestans. Currently, isoflavones have the most clinical trial data, but whether isoflavones can improve the symptoms of GSM has been controversial. CARMIGNANI et al.[30] found that oral isoflavones could effectively relievevaginal dryness, but could not improve vaginal atrophy. SUWANVESH et al.[31] found that 6% Pueraria mirifica gel could also increase the vaginal maturity index when applied to the vagina, suggesting that local use of isoflavones may have an estrogenic effect on the vagina. However, SRITONCHAI et al.[32] found that isoflavones only showed a significant estrogenic effect in restoring normal vaginal flora, but did not relieve symptoms when using 5% Pueraria mirifica gel for topical use. Therefore, according to these randomized controlled trials, it can be inferred that the efficacy of PE on GSM may be produced in a dose-effect manner, and the effect on vaginal atrophy varies with different types and modes of administration. Additionally, taking into account the different methods of each trial, different sample sizes and other factors, and the degree of symptom relief is a subjective result, which is greatly affected by individual factors, a clear conclusion on the efficacy and mechanism of PE can not be obtained at present.
3 Physical therapy modalities
3.1 Transvaginal therapies based on energy
In recent years, three kinds of energy-based transvaginal therapies have been proposed for the treatment of GSM, which are microablative fractional CO2 laser, non-ablative vaginal Erbium: YAG laser (Er: YAG), and radiofrequency. At present, a number of clinical trials have revealed the benefits of these treatments in different female populations, including women who have contraindications to hormone therapy or have a history of gynecological tumors[33-38].
In randomized controlled trials of laser therapy and vaginal estrogen therapy, it was found that the efficacy of laser was comparable to that of local estrogen and produced a more lasting effect than hormone therapy (lasting at least 6-12 months)[39-41]. This is because a certain degree of thermal energy is deposited on the vaginal wall, which can stimulate epithelial cell proliferation, neovascularization, and collagen formation, and vaginal histology is improved, which is the immediate repair response of heat to mucosal tissue[42-43]. In addition, ATHANASIOU et al.[44] found that laser therapy could also improve the vaginal microecosystem and restore vaginal health, while BECORPI et al[45] found that the relief of GSM symptoms was mainly related to the significant changes in the expression of vaginal inflammatory and regulatory cytokines, which made the vaginal epithelium in a highly remodeled state without significant changes in vaginal flora. Therefore, there is no clear conclusion on the mechanism of laser therapyat present, and further research is needed. Furthermore, some experiments have proved that the efficacy of CO2 laser treatment may be produced in a dose-effect manner[46], and there is no significant correlation with power[47-48]. According to different types of energy therapies, after receiving 3-6 regular courses of treatment, the curative effect can last for 12 months[36-49-50], and the additional course of treatment can further improve the asymptomatic rate[46].
At present, energy-based transvaginal therapies show excellent prospects in the treatment of GSM, but 4 clinical trials have reported related complications, such as fibrosis, scar formation, adhesion, and penetrating injury[51]. According to the existing research, there seems to be the most
evidence to support CO2 laser, followed by Erbium laser, and the least is radiofrequency, but it is not clear which is good or bad. It is necessary to design a more careful comparative study to compare the advantages and disadvantages of various treatment methods, and further investigate the potential benefits, harm, and effectiveness of laser or radiofrequency to GSM.
3.2 Pelvic floor muscle training (PFMT)
Menopause and aging will directly or indirectly affect the pelvic floor muscle (pelvic floor muscle, PFM), and the increase of PFM dysfunction may also lead to an increase in the prevalence of GSM[52]. PFMT is a kind of training designed to increase the strength, endurance, and flexibility of pelvic floor muscles[53]. There is already a single-arm feasibility study and a case study has been reported that the symptoms of GSM and its effect on the quality of daily life and sexual function can be significantly reduced after PFMT treatment, which proves that PFMT is a potential intervention to improve GSM[54-55].
3.3 Lifestyle modifications
Lifestyle modifications refer to the application of interventions in the management of related health problems, such as choosing a healthy diet, participating in physical activities regularly, and quitting smoking. The above lifestyle changes can be used to treat pelvic floor dysfunction, either in combination with other treatments or as a separate therapy[53]. This is a relatively low-cost, non-invasive, and harmless intervention, and general practitioners can individually develop targeted lifestyle adjustment plans for every woman with GSM.
4 New direction
4.1 Vitamin E vaginal suppository
The result of a randomized, single-blind clinical trial shows that vitamin E vaginal suppository can replace estrogen cream to alleviate the symptoms of vaginal atrophy of GSM[56]. However, due to the limited data, it is not recommended for clinical use, but it can become a new research direction.
4.2 ZP-025 vaginal gel— Monurelle Biogel (ZP-025)
Monurelle Biological vaginal gel is a kind of gel containing 2.3% purified bovine colostrum. It has been found in animal experiments that it can significantly improve vaginal hemodynamics, increase the thickness of the vaginal epithelium, and lubricate vaginal mucosa[57]. At present, some clinical trials have proved that ZP-025 is an effective method for the treatment of postmenopausal women with VVA, which can improve sexual life and urinary symptoms[58-59]. However, a large number of studies are still needed to verify this result in the future.
4.3 Micro-fat and nano-fat transplantation
In recent years, a micro-fat and nano-fat transplantation technique has been proposed to regenerate the vulvovaginal area and restore the appearance and function of the labia majoris, in order to increase the vaginal health index (VHI) and improve vaginal atrophy and sex-related problems. Clinical results have shown that after transplantation, the scores of VHI andFemale Sexual Distress Scale-Revisedwere significantly higher than those at baseline, and patients still benefited during the 18-month follow-up after treatment, and no adverse events occurred[60]. At present, this method shows a good prospect in the treatment of GSM, but more studies are needed to verify its safety and effectiveness.
5. Conclusion
GSM is a chronic progressive disease that requires lifelong management. General practitioners should pay attention to the physiological changes of women at this stage, actively inquire about
relevant symptoms in the process of consultation, GSM screening, and popularization of related knowledge for peri-menopausal and postmenopausal women, so as to increase their awareness of this aspect and improve their self-management ability. In addition, in terms of treatment, each of the above methods has its own advantages and disadvantages, and it is necessary to comprehensively consider the overall health status and personal wishes of the patients before making a choice.
Nowadays, combining the vast majority of the current guidelines and the treatment methods retrieved in this article, it is suggested that in daily diagnosis and treatment, general practitioners can tell women who do not have obvious symptoms of GSM before menopause what changes will happen to their pelvic floor muscles in the next stage and point out what controllable risks they have in their lives, and then they can first choose conservative treatments to carry out early intervention on the risk factors. Encourage women to maintain a healthy lifestyle and PFMT, which may reduce the incidence or severity of GSM. For women who have mild GSM symptoms, it is recommended to use non-hormonal vaginal lubricants and moisturizers to alleviate the symptoms. When women use over-the-counter drugs that are ineffective or have moderate to severe GSM symptoms, a very small dose of vaginal estrogen can be preferred.When women combined with other complications, such as vasomotor symptoms, then choose systemic MHT, and for women withuteri, EPT or CEE/BZA is more recommended. In addition, for women with hormone contraindications, we can also try to use ospemifene and vaginal DHEA, which will not cause changes in serum hormone levels, and have no significant stimulating effect on breast or endometrium.
For some emerging treatments, such as energy-based transvaginal therapies, micro-fat, and nano-fat transplantation, compared with the traditional hormone therapies, they have a longer curative effect and are more widely applicable to the population, and have good prospects. However, for PEs, vaginal oxytocin gel, vitamin E vaginal suppository, Monurelle Biological vaginal gel, and other treatment regimens, there are still many blind spots, which are not recommended for routine clinical treatment.
Author contribution:LIU Shuangxue is responsible for the conception and design of the article, the collection and arrangement of documents/materials, the writing, revision, and English translation of the paper. LIU Shuangxue and LIYanhua are responsible for the quality control and revision of the article.LIYanhua is responsible for the article as a whole, supervising and managing it.
Conflicts of Interest: The authors declare no conflict of interest.
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12. Effect of Probiotic Intervention on Class Ⅳ andⅤLupus Nephritis
Meng HUANG, Cunjun HUANG, Qiujuan OU, Hongbo DAI, Jiede HE, Hang LIANG, Zhe CHEN, Qiubi XU
Chinese General Practice    2022, 25 (20): 2462-2467.   DOI: 10.12114/j.issn.1007-9572.2022.02.001
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Background

As an adjuvant therapy, probiotics can significantly improve the therapeutic effect in lupus nephritis. But there is a lack of comparative studies of efficacies of drug treatments and effects of probiotics on gut flora.

Objective

To observe the therapeutic efficacy, and gut flora changes induced by probiotics as an adjuvant therapy for lupus nephritis.

Methods

Ninety-eight patients with class Ⅳ andⅤlupus nephritis were selected from Department of Nephrology, Affiliated Hospital of Xiangnan University from 2019 to 2020, and randomized into a routine group (routine treatment) and an intervention group (routine treatment plus probiotics) under allocation concealment. Intergroup comparison of clinical efficacies was conducted after 24-week treatment in terms of levels of 24-hour urine protein, blood urea nitrogen, serum creatinine, serum IgE, IgG, and serum inflammatory markers, as well as fecal flora changes and fecal short-chain fatty acid concentrations.

Results

A total of 93 cases (46 in routine group, and 47 in intervention group) who completed the therapeutic follow-up were included for final analysis. Both groups had no statistically significant differences in sex ratio, mean age, BMI, baseline levels of systolic blood pressure, diastolic blood pressure, hemoglobin, serum albumin, serum creatinine, complement C3 and complement C4 (P>0.05) . At the end of treatment, the intervention group demonstrated lower mean Systemic Lupus Erythematosus Disease Activity Indexof Renal (P<0.05) . The 24-hour urinary protein, blood urea nitrogen and serum creatinine decreased notably in both groups at the end of 4, 12 and 24 weeks of treatment (P<0.05) , and the 24-hour urinary protein and blood urea nitrogen in intervention group at the end of 24-week treatment were even more lower (P<0.05) . When the 24-week treatment ended, serum IgE and IgG levels decreased notably in both groups (P<0.05) , and they deceased even more significantly in intervention group (P<0.05) . Moreover, serum C-reactive protein, IL-6 and TNF-α decreased significantly in both groups (P<0.05) , and they deceased even more significantly in the intervention group (P<0.05) . Linear discriminant analysis effect size analysis indicated that at baseline, harmful gut flora such as Helicobacter pylori, Clostridium, and Enterococcus, significantly increased while Verrucomicrobia and other beneficial gut flora significantly decreased in all participants. After the 24-week treatment, the above-mentioned harmful gut flora decreased and beneficial gut flora increased in all participants, and such changes were more significant in the intervention group. Fecal acetic acid, propionic acid, and butyric acid increased significantly in all participants compared to the baseline levels, and they increased even more significantly in the intervention group (P<0.05) .

Conclusion

Adjuvant treatment of lupus nephritis with probiotics could promote the recovery of renal function, by elevating the abundance of Akkermansiaceae, contents of fecal acetic acid, propionic acid, and butyric acid, and lowering serum immunoglobulin.

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13. Phenotypically Male Congenital Adrenal Hyperplasia Patient with Huge Space-occupying Adrenal Masses: a Case Report and Literature Review
RAO Yufeng, MENG Liheng, ZHOU Jia, LIANG Xinghuan, HUANG Zhenxing, QIN Yingfen
Chinese General Practice    2023, 26 (21): 2690-2694.   DOI: 10.12114/j.issn.1007-9572.2022.0723
Abstract889)   HTML11)    PDF(pc) (1727KB)(275)    Save

Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disease encompassing enzyme deficiencies in the process of adrenal steroidogenesis, which leads to adrenal cortex dysfunction. Hypersecretion of corticotrophin-releasing hormone and insufficient cortisol production often lead to enlarged adrenal glands. Existing studies have reported that most of space-occupying adrenal masses in CAH are benign, only very few are malignant. It is difficult for clinicians to distinguish the nature of space-occupying adrenal masses, and physicians have insufficient experiences in treating the disease. We reported a phenotypically male case of CAH with huge space-occupying adrenal masses and reviewed relevant literature, aiming to provide evidence on the diagnosis and treatment of this disease for clinicians. The space-occupying adrenal masses in CAH often show tumor-like hyperplasia before diagnosis and treatment or effective hormone replacement therapy, but most of them will be significantly reduced or disappear after glucocorticoid replacement therapy. But a follow-up of several years showed that space-occupying adrenal masses in the CAH patient encountered by us had no significant changes and no significant impact on the patient's body, even without effective drug intervention.

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14. Efficacy and Safety of Xiezhuoxiaozheng Therapy in Diabetic Kidney Disease: a Clinical Study
Hanwen YANG, Yaoxian WANG, Qiaoru WU, Jiale ZHANG, Runze YAN, Xiaona WANG, Zhen WANG, Weiwei SUN
Chinese General Practice    2022, 25 (26): 3252-3257.   DOI: 10.12114/j.issn.1007-9572.2022.0193
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Background

The incidence of diabetic kidney disease (DKD) is increasing, which has become a major cause of end-stage renal disease. DKD has an insidious onset, and progresses rapidly since the presence of proteinuria, it is difficult to slow down its progression with conventional therapy especially when renal function is significantly impaired. Therefore, it is urgently necessary to explore an effective treatment for delaying the progression of advanced DKD. The Xiezhuoxiaozheng therapy, proposed by Professor WANG Yaoxian in accordance with the pathogenesis of advanced DKD manifested by turbid poison and mass signs and symptoms (zhengjia) , has proven to be effective in clinical treatment of advanced DKD.

Objective

To assess the clinical efficacy and safety of Xiezhuoxiaozheng therapy in advanced DKD based on the theory of "latent internal heat causing renal collateral mass".

Methods

A real-world, prospective cohort study design was used to investigate the clinical efficacy and safety of Xiezhuoxiaozheng therapy for advanced DKD in seven hospitals (Dongzhimen Hospital, Beijing University of Chinese Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing Hospital of Traditional Chinese Medicine, Wangjing Hospital of CACMS, Xiyuan Hospital of CACMS, Beijing Hospital of Integrated Traditional Chinese and Western Medicine, and Beijing Fangshan District Hospital of Traditional Chinese Medicine) from 2016 to 2020. Patients with DKD who met the inclusion criteria were recruited and divided into a control group (basic western medical treatment) and a test group (basic western medical treatment plus Xiezhuoxiaozheng therapy) taking the method of Xiezhuoxiaozheng and eliminating symptoms as the exposure factor, and received 24-week interventions. At baseline, and the end of 4, 12, and 24 weeks of interventions, serum creatinine (Scr) , blood urea nitrogen (BUN) , 24-hour urine protein, and total cholesterol (TC) , estimated glomerular filtration rate (eGFR) were measured, TCM symptom score was assessed. HbA1c was measured at baseline, and the end of 12, and 24 weeks of interventions. Adverse events were recorded during treatment, and safety was evaluated.

Results

A total of 59 cases completed the study, including 36 in the test group and 23 in the control group. The intervention duration had significant main effect on eGFR, Scr, and BUN levels in both groups (P<0.05) . The intervention therapy and duration had significant interaction effect on the change in the TCM symptom score in both groups (P<0.05) . The control group had increased BUN level at the end of 12 weeks of intervention, and increased BUN, Scr and heat syndrome score at the end of 24 weeks of intervention (P<0.05) . In contrast, the test group had increased eGFR at the end of 4 weeks of intervention (P<0.05) . The test group had higher eGFR and lower Scr, BUN and TCM symptom score at the end of intervention than did the control group (P<0.05) . The incidence of adverse reactions was 21.74% (5/23) in the control group and 8.33% (3/36) in the experimental group. There was no significant difference between the two groups (χ2=2.15, P=0.14) .

Conclusion

For advanced DKD, Xiezhuoxiaozheng therapy combined with usual western medicine treatment may be superior to usual western medicine treatment alone in delaying the decrease of eGFR, slowing down the increase of Scr and BUN levels, protecting kidney function, reducing the heat syndrome score and improving the TCM symptoms, which could improve the clinical efficacy.

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15. Interpretation of the Management of Nephrolithiasis in Pregnancy: Multi-disciplinary Guidelines from an Academic Medical Center: Improving the Diagnostic and Therapeutic Capacity, and Strengthening Multi-disciplinary Collaborative Management
LIANG Puzhao, TIAN Zhentao, WU Yuyi
Chinese General Practice    2023, 26 (05): 519-524.   DOI: 10.12114/j.issn.1007-9572.2022.0569
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Nephrolithiasis in pregnancy is a common non-obstetric indication for hospital admission in obstetric patients, which is often associated with pain, nausea, vomiting, decreased renal function, urinary infection and other symptoms, and improper treatment for which will lead to abortion, premature delivery and other adverse pregnancy outcomes. In response, a multi-disciplinary team from a single academic medical center in the United States was assembled to create the management of nephrolithiasis in pregnancy: multi-disciplinary guidelines from an academic medical center to standardize the care for obstetric patients presenting with suspected nephrolithiasis. A total of 10 guideline statements were constructed, including four for guiding diagnosis and imaging, and six for guiding clinical treatment. It is noteworthy that compared with relevant Chinese guidelines, the guidelines provide practice-based evidence that proves the safety and effectiveness of low-dose non-contrast CT scan preferably used when condition changes and diagnostic uncertainty exists. This paper offers an in-depth interpretation of the above-mentioned contents in the guidelines.

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16. Safety of Weekly Single versus Divided Administration of Moderate-dose Erythropoietin in the Treatment of Maintenance Hemodialysis Patients with Renal Anemia
WU Xiuling, LI Jianjun, YU Ying, XING Rong, WANG Lu, WANG Xuedong, TENG Fubin
Chinese General Practice    2023, 26 (06): 711-717.   DOI: 10.12114/j.issn.1007-9572.2022.0542
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Background

From previous studies, the frequency of administration of recombinant human erythropoietin injection (rHuEPO) has no association with its therapeutic effect in renal anemia in chronic kidney disease (CKD), and there is no significant difference in the efficacy between weekly single dosing and divided dosing. Most hemodialysis patients are clinically treated with moderate-dose rHuEPO, but there is a lack of research on the safety of single and divided administration of moderate-dose rHuEPO.

Objective

To compare the safety between weekly single and divided administration of moderate-dose rHuEPO for renal anemia in maintenance hemodialysis patients.

Methods

This study was designed as a randomized, parallel-group controlled, non-inferiority clinical trial. Eighty-eight patients with renal anemia who underwent maintenance hemodialysis at the Hemodialysis Room, Tongzhou Branch, Dongzhimen Hospital, Beijing University of Chinese Medicine from January 2019 to May 2021 were selected and randomly divided into an experimental group and a control group with 44 in each. For comparing the safety and efficacy of weekly single and divided administration of moderate-dose rHuEPO, 29 cases (experimental subgroup 1) and other 15 cases (experimental subgroup 2) in the experimental group received an rHuEPO dose of 6 000 U, and an rHuEPO dose of 4 000 U, once a week, respectively; 30 cases (control subgroup 1) in the control group received a single rHuEPO dose of 2 000 U, three times a week (6 000 U per week in total), and other 14 cases (control subgroup 2) received a single rHuEPO dose of 2 000 U, twice a week (4 000 U per week in total) .

Results

Safety analysis: two-factor repeated-measures ANOVA showed that the type of intervention scheme and duration had no interaction effects on systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pre-dialysis serum potassium between experimental subgroup 1 and control subgroup 1, and between experimental subgroup 2 and control subgroup 2 (P>0.05), and produced no main effects on systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pre-dialysis serum potassium in experimental subgroup 1 and control subgroup 1, and between experimental subgroup 2 and control subgroup 2 (P>0.05). The serum levels of AST, ALT and TBiL were similar between experimental subgroup 1 and control subgroup 1 at baseline and 12 weeks of treatment (P>0.05). Likewise, they were similar between experimental subgroup 2 and control subgroup 2 at baseline and 12 weeks of treatment (P>0.05). No thromboembolic, cardiovascular or cerebrovascular events and gastrointestinal reactions related to rHuEPO occurred in any of the subgroups during the 12-week treatment. Efficacy analysis: the hemoglobin level (reference range was 110-130 g/L) in experimental subgroup 1 〔65.5% (19/29) 〕was similar to that in control subgroup 1 〔73.3% (22/30) 〕at 12 weeks of treatment (χ2=0.425, P=0.514). The serum levels of hemoglobin were similar between experimental subgroup 2 and control subgroup 2 at 12 weeks of treatment (P>0.05). The levels of red blood cell count, hematocrit, percentage and absolute number of reticulocytes, ferritin and transferrin saturation did not vary between experimental subgroup 1 and control subgroup 1, and between experimental subgroup 2 and control subgroup 2 either at baseline or 12 weeks of treatment (P>0.05) .

Conclusion

Weekly single and divided administration of moderate-dose erythropoietin had no significant difference in medication safety in the treatment of renal anemia in maintenance hemodialysis patients.

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17. Factors Associated with Cognitive Impairment in Chinese Patients with End-stage Renal Disease: a Meta-analysis
Hui ZHANG, Wei YANG, Dan WEI, Zijuan ZHOU, Haiou ZOU
Chinese General Practice    2022, 25 (21): 2651-2660.   DOI: 10.12114/j.issn.1007-9572.2022.0203
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Background

Cognitive impairment (CI) is highly prevalent in patients with end-stage renal disease (ESRD) , which seriously affects the prognosis of patients. Early identification of its associated factors is of great significance, but there is no agreement as to existing relevant research conclusions, and no relevant systematic reviews conducted with Chinese patients with ESRD.

Objective

To systematically evaluate the factors associated with CI in Chinese patients with ESRD.

Methods

Databases of PubMed, Web of Science, EMBase, CNKI, WanFangData, CQVIP and CBM were searched from inception to October 2021 for studies (including cross-sectional studies, cohort studies and case-control studies) about associated factors of CI in Chinese ESRD patients (with stage CKD5 defined in the 2002 Kidney Disease Outcomes Quality Initiative, or treatment with peritoneal dialysis or hemodialysis) using subject words in combination with free words as search terms with adjustment by the database feature when necessary. Two researchers independently performed literature screening, data extraction, and methodological quality assessment. Stata 15.0 was employed for Meta-analysis.

Results

In total, 44 studies were included, including 42 172 patients, among which, the cohort studies and case-control studies were rated as high-quality evidence, and the cross-sectional studies as moderate or high-quality evidence. Meta-analysis revealed that older age〔OR=1.17, 95%CI (1.13, 1.22) , P<0.001〕, long duration of dialysis〔OR=1.02, 95%CI (1.00, 1.03) , P=0.008〕, hypertension〔OR=2.02, 95%CI (1.06, 3.86) , P=0.032〕, stroke〔OR=1.93, 95%CI (1.33, 2.80) , P=0.001〕, diabetes〔OR=1.99, 95%CI (1.62, 2.44) , P<0.001〕, high Charlson Comorbidity Index (CCI) 〔OR=5.28, 95%CI (1.48, 18.82) , P=0.010〕, depression〔OR=2.46, 95%CI (1.61, 3.77) , P<0.001〕, high parathyroid hormone (PTH) 〔OR=1.02, 95%CI (1.00, 1.04) , P=0.034〕, high C-reactive protein (CRP) 〔OR=1.20, 95%CI (1.01, 1.42) , P=0.040〕and high Hcy 〔OR=3.34, 95%CI (2.06, 5.42) , P<0.001〕 were associated with increased risk of CI, while male〔OR=0.55, 95%CI (0.37, 0.82) , P=0.003〕, high education level〔OR=0.45, 95%CI (0.37, 0.55) , P<0.001〕, high Hb〔OR=0.91, 95%CI (0.86, 0.95) , P<0.001〕, high serum ALB〔OR=0.77, 95%CI (0.63, 0.94) , P=0.009〕 and high serum creatinine〔OR=0.997, 95%CI (0.995, 0.999) , P=0.003〕were associated with decreased risk of CI.

Conclusion

The current evidence proves that the risk of CI in Chinese patients with ESRD may be increased with older age, long duration of dialysis, hypertension, stroke, diabetes, high CCI, depression, high PTH, high CRP and high Hcy, and decreased with male, high education level, and high Hb, ALB and Cr. However, the conclusion needs to be verified by more high-quality studies due to limited number and quality of included studies.

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18. Effectiveness of Febuxostat in the Treatment of Non-end-stage Diabetic Nephropathy with Hyperuricemia and Its Effect on Renal Function 
MIAO Yan,WU Jun,YAN Lei,DONG Yang,ZHU Qing,SHAO Fengmin
Chinese General Practice    2019, 22 (10): 1192-1197.   DOI: 10.12114/j.issn.1007-9572.2019.10.012
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Background Febuxostat is safe and effective for non-end-stage chronic kidney disease,which can reduce the serum uric acid and delay the progression of renal insufficiency.Diabetic nephropathy (DN)patients are more prone to hyperuricemia (HUA).Objective To investigate the urate-lowering efficacy and renal effect of febuxostat in non-end-stage DN with HUA.Methods A prospective,randomized,controlled trial was conducted from February 2017 to February 2018 among non-end-stage DN with HUA inpatients and outpatients (n=140) treated in nephrology,endocrinology departments,or community health organizations of Henan Provincial People's Hospital.Participants were randomly assigned to either treatment group or control group,and received the same treatment,except that the former group received febuxostat(40 mg,once daily),while the latter received no pharmaceutical therapy for lowering uric acid.Serum uric acid (SUA),serum creatinine (Scr),albumin-to-creatinine ration (ACR) and other clinical parameters were measured at baseline and 1-6 months after treatment.The changes of SUA,ACR and estimated glomerular filtration rate (eGFR) were compared between the two groups.Results Overall,112 cases completed the trial,including 58 in the treatment group and 54 in the control group.There were no significant differences in sex ratio,average age,body mass index (BMI),baseline blood pressure levels,SUA,Scr,ACR and eGFR between the two groups (P>0.05).The analysis showed that the number and the rate of achieving target SUA level in the treatment group were 42 (77.8%),47 (87.0%),51 (94.4%),52 (96.3%),52 (96.3%),52 (96.3%),respectively,at the end of 1st,2nd,3rd,4th,5th,and 6th months of treatment.Compared with baseline,post-treatment eGFR level increased significantly in the treatment group 〔(56.42±14.49) ml?min-1?(1.73 m2)-1 vs (50.95±13.66)ml?min-1?(1.73 m2)-1〕.Treatment group showed much lower post-treatment HbA1c,TC,LDL-C,SUA,Scr and ACR levels compared with the control group (P<0.05).Pearson correlation analysis showed that the duration of diabetes,SBP,HbA1c,and SUA were positively correlated with ACR,while eGFR was negatively correlated with ACR (P<0.05);the duration of diabetes,HbA1c,LDL-C,SUA,SCr and ACR were negatively correlated with eGFR (P<0.05).Stepwise multiple linear regression analysis showed that duration of diabetes,HbA1c and SUA were the influencing factors of ACR (P<0.05),and duration of diabetes,SUA and Scr were the independent influencing factors of eGFR (P<0.05).Conclusion For those also with HUA,this treatment could effectively reduce the SUA level,decrease the incidence of proteinuria,and delay the progression of renal insufficiency.
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19. Analysis of the Correlation between Time in Range and Diabetic Kidney Disease
SHU Tao, GUO Zheng, WANG Fei, CHEN Shuyan
Chinese General Practice    2023, 26 (15): 1873-1879.   DOI: 10.12114/j.issn.1007-9572.2022.0749
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Background

Time in range (TIR) is a new indicator of glycemic management in diabetes mellitus which has been thriving in recent years. Studies have confirmed that TIR is closely associated with chronic complications of diabetes. Previous studies have confirmed a close association between TIR and chronic complications of diabetes. Current studies on TIR and diabetic kidney disease (DKD) mainly focus on proteinuria, however the role of glomerular filtration rate (eGFR) in it is often neglected, and there are few studies on the cut points of TIR in evaluating glycemic control.

Objective

To investigate the relationship between TIR and the development of DKD in type 2 diabetes mellitus (T2DM), so as to provide theoretical foundations for the timely clinical detection, diagnosis and treatment of DKD in patients with T2DM.

Methods

A total of 214 T2DM patients admitted to the Department of Endocrinology in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2021 to December 2021 were included. The general data, laboratory indices and medication use were collected. The included patients were divided into group of DKD〔UACR ≥ 30 mg/g and/or eGFR < 60 ml·min-1 (1.73 m2) -1, n=58〕 and group of T2DM alone〔UACR<30 mg/g and eGFR≥60 ml·min-1 (1.73 m2) -1, n=156〕 based on the urinary albumin/creatinine ratio (UACR) and eGFR results, the included patients were further divided into TIR1 group (TIR>85%, n=90), TIR2 group (70%<TIR≤85%, n=51), TIR3 group (40%<TIR≤70%, n=57), and TIR4 group (TIR≤40%, n=16) using TIR values of 40%, 70%, and 85% as the cut points. Multivariate Logistic regression analysis was used to analyze the relationship between TIR and the development of DKD in T2DM patients.

Results

The detection rate of DKD in T2DM patients tended to increase with decreasing TIR levels (Ptrend <0.05). The results of multivariate Logistic regression analysis showed that TIR was an influencing factor for the development of DKD in T2DM patients after adjusting for variables〔OR=0.976, 95%CI (0.953, 0.999), P=0.047〕; TIR3 and TIR4 groups were influencing factors for the development of DKD in T2DM patients compared to TIR1 group〔OR=5.287, 95%CI (1.897, 14.737), P=0.001; OR=4.712, 95%CI (1.143, 19.424), P=0.032〕 after adjusting for various confounding variables, and the incidence risk of DKD in T2DM patients tended to increase with decreasing TIR levels (Ptrend=0.010) .

Conclusion

TIR is an influencing factor for the development of DKD in T2DM patients; the incidence rate of DKD in T2DM patients increases significantly with the decreasing levels of TIR.

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20. Clinical, Pathological and TCM Syndromes of Primary IgA Nephropathy with Malignant Hypertension
Jianghua KE, Shuwei DUAN, Linchang LIU, Shuang LI, Yujing KE, Yilun QU, Jin YAO, Xiangmei CHEN
Chinese General Practice    2022, 25 (27): 3395-3403.   DOI: 10.12114/j.issn.1007-9572.2022.0201
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Background

IgA nephropathy (IgAN) is the most common primary glomerular disease, and one major cause of malignant hypertension (MHT) secondary to renal parenchymal disease. The clinical conditions and severity of renal lesion have been reported to be more serious when IgAN is accompanied by MHT, but risk factors of MHT in IgAN analyzed from Traditional Chinese Medicine (TCM) perspective are still unclear.

Objective

To explore the TCM-related factors and pathogenesis associated with MHT in IgAN patients.

Methods

From 518 cases of primary IgAN who were diagnosed by renal biopsy in First Medical Center of Chinese PLA General Hospital during December 2013 to September 2021, a sample of 12 cases accompanied by MHT (IgAN-MHT group) computed by PASS 15.0 were selected for correlation power analysis, and they were matched at a ratio of 1∶5 with other randomly selected 85 cases without MHT (IgAN group) . Clinical, pathological and TCM syndromes between the two groups were compared. Lasso regression was used to screen 93 TCM syndromes, among which those with significant associations with IgAN-MHT were identified by multivariate Logistic regression.

Results

Compared with IgAN group, IgAN-MHT group had higher prevalence of headache and dizziness or nausea and vomiting as the first clinical manifestations, and clinically diagnosed nephrotic syndrome, higher levels of baseline mean arterial pressure, highest systolic and diastolic blood pressure, blood urea nitrogen, serum creatinine, serum inorganic phosphorus, serum magnesium, and quantitatively estimated 24-hour urinary protein excretion, higher prevalence of CKD stages 3-5, blood stasis syndrome, subtypes of qi-deficiency syndromes (including mental fatigue and lack of strength, limb fatigue, tibia and leg weakness, dizziness, headache with nausea, and vomiting) , subtypes of yin-deficiency syndromes (including blurred vision and eye floaters) , subtypes of blood stasis syndromes (including nail cyanosis, and dark purple tongue) , and intrarenal arteriosclerosis (P<0.05) . Moreover, IgAN-MHT group had lower prevalence of abnormal urine test results as the first clinical manifestations, previous hypertension and clinical diagnosed chronic nephritic syndrome, as well as lower levels of mean serum IgM and IgG levels, and eGFR (P<0.05) . Both groups had no significant difference in the prevalence of interstitial fibrosis/tubular atrophy (T) lesions among the two groups (P<0.05) . The common TCM syndrome in IgAN-MHT group was qi-yin deficiency syndrome combined with blood stasis syndrome. Correlation analysis showed that IgAN-MHT was positively associated with blood stasis syndrome (P<0.05) ; in IgAN-MHT group, male and quantitatively estimated 24-hour urinary protein excretion was positively associated with qi-deficiency syndrome (P<0.05) ; serum inorganic phosphorus and potassium was negatively associated with yin-deficiency syndrome (P<0.05) , and renal tubular atrophy/interstitial fibrosis was positively associated with blood stasis syndrome (P=0.040) . Multivariate Logistic regression analysis showed that headache〔OR=7.895, 95%CI (1.643, 37.935) , P=0.010〕, blurred vision〔OR=5.499, 95%CI (1.207, 25.053) , P=0.028〕, dry mouth with desire for drink 〔OR=10.079, 95%CI (2.289, 44.373) , P=0.002〕, and nail cyanosis〔OR=18.312, 95%CI (2.179, 153.884) , P=0.007〕 were associated with MHT in IgAN.

Conclusion

IgAN-MHT patients had worse renal function and more serious renal pathological damage. The common TCM syndrome in IgAN-MHT was qi-yin deficiency syndrome with blood stasis syndrome. The clinical and pathological indices of IgAN-MHT patients had a certain level of correlation with qi-deficiency syndrome, yin-deficiency syndrome and blood stasis syndrome. The subtypes of TCM syndromes, such as headache, blurred vision, dry mouth with desire for drink, and nail cyanosis were the influencing factors of MHT in IgAN. Early detection, diagnosis and treatment, concern for and improvement of symptoms related to syndromes of qi-deficiency, yin-deficiency, and blood stasis, may contribute to decreased risk of MHT in IgAN.

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21. Effect of Impaired Fasting Glucose on Estimated Glomerular Filtration Rate
LIU Linhua, ZHAN Jinfeng, XIA Zhongbin
Chinese General Practice    2023, 26 (03): 304-307.   DOI: 10.12114/j.issn.1007-9572.2022.0492
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Background

Estimated glomerular filtration rate (eGFR) is a quantitative indicator assessing the severity of chronic kidney disease. Studies have shown that elevated glucose in prediabetic period increases the risk of chronic kidney disease, but its direct effect on eGFR has been less reported.

Objective

To investigate the effect of fasting blood glucose level on eGFR in a community-dwelling population with impaired fasting glucose (IFG) .

Methods

Participants (n=28 601) were selected from a group of physical examinees from Physical Examination Center, the Second Affiliated Hospital of Nanchang University during January to December 2020 according to the inclusion criteria and exclusion criteria. Demographic and clinical data〔past medical history, sex, age, BMI, blood pressure, serum uric acid, lipids, and creatinine, fasting plasma glucose (FPG) , routine urine parameters〕were collected and compared between subjects with elevated FPG (5.6 mmol/L≤FPG<7.0 mmol/L) and those with normal FPG (3.9 mmol/L≤FPG<5.6 mmol/L) . The influence of FPG on eGFR was assessed by the Mann-Whitney U-test comparing multiple factors〔sex, age, mean arterial pressure (MAP) , serum uric acid, total cholesterol, BMI〕 between subjects with elevated and normal FPG after matching. The correlation between FPG and eGFR was assessed in subjects with elevated and normal FPG before and after matching.

Results

There were 25 539 individuals with normal FPG, and 3 062 with elevated FPG. There were significant difference in age, MAP, serum uric acid, total cholesterol, BMI and eGFR between the two groups (P<0.05) . Individuals with elevated FPG had higher eGFR than those with normal eGFR (P<0.05) after matching age, MAP, serum uric acid, total cholesterol, and BMI between the two groups (P<0.05) . Correlation analysis showed that FPG had a weak negative correlation with eGFR in all participants (rs=-0.047, P<0.05) , but had a weak positive correlation with eGFR in the matched population (rs=0.065, P<0.05) , and the correlation coefficient increased further in the matched individuals with elevated FPG (rs=0.127, P<0.05) .

Conclusion

IFG may be associated with elevated eGFR, which provides a possible basis for the glomerular hyperfiltration state that occurs with elevated glucose in prediabetes.

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22. Clinical Value of Systemic Immune-inflammation Index in the Diagnosis of Diabetic Kidney Disease in Community-dwelling Elderly Patients with Type 2 Diabetes
ZHAO Lizhen, LI Weimin, JIANG Ruixia
Chinese General Practice    2023, 26 (18): 2227-2231.   DOI: 10.12114/j.issn.1007-9572.2022.0873
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Background

Diabetic kidney disease (DKD) is a common diabetic complication, which is mainly characterized by damage in renal microvessels. Early diagnosis and active prevention of DKD are the key to improving the prognosis. The blood inflammatory index may be related to DKD.

Objective

To explore the value of systemic immune-inflammation index (SII) for the diagnosis of DKD in elderly type 2 diabetes mellitus (T2DM) patients in the community.

Methods

A retrospective study was conducted with 327 elderly patients with T2DM who underwent routine physical examination in Community Medical Department, Beijing Chao-yang Hospital (West Branch), Capital Medical University from January to December 2021. They were divided into non-DKD group (n=112) and DKD group (n=215) by the prevalence of DKD. The general data and laboratory examination data of the two groups were collected and compared. Pearson correlation analysis and Spearman rank correlation analysis were used to assess the correlation of urinary albumin/creatinine ratio (UACR) with other various indicators. Multivariate Logistic regression analysis was used to explore the influencing factors of DKD in the patients. The diagnostic value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and SII for DKD in these patients was evaluated by using the receiver operating characteristic (ROC) curve, and the area under the curve (AUC) with corresponding 95%CI was calculated.

Results

The course of T2DM in DKD group was longer than that in non-DKD group (P<0.05). Moreover, the proportion of patients with hypertension history, fasting plasma glucose (FPG), low-density lipoprotein (LDL), blood urea nitrogen, serum creatinine (Scr), UACR, neutrophils, platelets, NLR, PLR and SII in DKD group were higher than those in non-DKD group (P<0.05). Correlation analysis showed that course of T2DM, FPG, triacylglycerol, LDL, neutrophils, platelets, NLR, PLR and SII were positively related with UACR (r=0.716, 0.114, 0.113, 0.144, 0.533, 0.226, 0.538, 0.430, 0.494, P<0.05). Multivariate Logistic regression analysis showed that course of T2DM〔OR=1.300, 95%CI (1.173, 1.441), P<0.001〕, LDL〔OR=2.565, 95%CI (1.320, 4.985), P=0.005〕, Scr〔OR=1.093, 95%CI (1.046, 1.143), P<0.001〕, NLR〔OR=2.565, 95%CI (1.320, 4.985), P=0.005〕and SII〔OR=1.011, 95%CI (1.007, 1.015), P<0.001〕were associated with DKD in elderly. In diagnosing DKD in these patients, the AUC of NLR was 0.755〔95%CI (0.696, 0.814) 〕, the optimal cut-off value was 2.49, with a sensitivity of 72.1% and a specificity of 70.5%; the AUC of PLR was 0.689〔95%CI (0.624, 0.754) 〕, the optimal cut-off value was 112.81, with a sensitivity of 90.2%, and a specificity of 43.8%; the AUC of SII was 0.836〔95%CI (0.791, 0.881) 〕, the optimal cut-off value was 492.08, with a sensitivity of 80.5% and a specificity of 73.2%.

Conclusion

The course of T2DM, LDL, Scr, NLR and SII may be the influencing factors of DKD in community-dwelling elderly T2DM patients. Moreover, SII has great clinical diagnostic value for DKD in this population.

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23. Risk Factors for Acute Kidney Injury in Severe Acute Pancreatitis: a Meta-analysis
Meiying CHEN, Muxin CHEN, Mingxin WANG, Chanmei ZHENG, Wanzhu CAI, Aixin LIANG, Chunjiao ZHOU
Chinese General Practice    2022, 25 (30): 3834-3842.   DOI: 10.12114/j.issn.1007-9572.2022.0452
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Background

Acute kidney injury (AKI) is a common complication and a key poor prognostic factor in severe acute pancreatitis (SAP) . It is rather challengeable to prevent and treat AKI in SAP, but early assessment and intervention of related risk factors can prevent or delay its development.

Objective

To systematically analyze the risk factors of AKI in SAP.

Methods

Databases of PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Data, CQVIP and SinoMed were searched for articles about the risk factors of AKI in SAP from inception to January 2022. Two researchers independently performed literature screening according to inclusion and exclusion criteria, data extraction, and methodological quality assessment. RevMan 5.4 and Stata 15.1 were employed for Meta-analysis.

Results

In total, 21 studies were included, including 3 823 patients. Meta-analysis demonstrated that being male〔OR=1.42, 95%CI (1.21, 1.68) , P<0.001〕, drinking history〔OR=1.51, 95%CI (1.14, 2.01) , P=0.004], higher APACHE Ⅱ score〔MD=5.69, 95%CI (2.95, 8.44) , P<0.001〕, Ranson score〔MD=2.58, 95%CI (2.27, 2.88) , P<0.001〕, and CTSI score〔MD=1.48, 95%CI (0.17, 2.80) , P=0.030〕; increased lencocyte count〔MD=0.96, 95%CI (0.47, 1.44) , P<0.001〕, IL-33〔MD=28.36, 95%CI (19.05, 37.67) , P<0.001〕, CRP〔MD=17.38, 95%CI (12.39, 22.38) , P<0.001〕, Scr〔MD=49.50, 95%CI (24.80, 74.19) , P<0.001〕, PCT〔MD=6.74, 95%CI (3.36, 10.12) , P<0.001〕, neutrophil gelatinase-associated lipocalin (NGAL) 〔MD=18.31, 95%CI (11.82, 24.80) , P<0.001〕, and serum lactate〔MD=0.87, 95%CI (0.27, 1.46) , P=0.004〕; prevalence of hypoxemia〔OR=9.42, 95%CI (4.81, 18.44) , P<0.001〕, hypertension〔OR=1.35, 95%CI (1.06, 1.72) , P=0.010〕, diabetes〔OR=1.56, 95%CI (1.20, 2.04) , P<0.001〕, and coronary heart disease〔OR=3.20, 95%CI (1.41, 7.24) , P=0.005〕; use of mechanical ventilation〔OR=5.00, 95%CI (2.76, 9.07) , P<0.001〕; prevalence of shock〔OR=11.60, 95%CI (3.37, 39.91) , P<0.001〕, infection〔OR=5.78, 95%CI (3.10, 10.79) , P<0.001〕, multiple organ dysfunction syndrome (MODS) 〔OR=7.28, 95%CI (3.56, 14.88) , P<0.001〕, abdominal bleeding〔OR=5.51, 95%CI (1.38, 22.09) , P=0.020〕, acute respiratory distress syndrome (ARDS) 〔OR=9.61, 95%CI (4.14, 22.27) , P<0.001〕, and abdominal compartment syndrome (ACS) 〔OR=5.79, 95%CI (3.75, 8.93) , P<0.001〕; long stay in the ICU〔MD=8.77, 95%CI (2.76, 14.79) , P=0.004〕were risk factors of AKI in SAP.

Conclusion

Male, drinking history, higher APACHEⅡ score, Ranson score and CTSI score, elevated inflammatory markers (lencocyte count, IL-33, CRP, Scr, PCT, NGAL) and elevated serum lactate, underlying disease prevalence (hypoxemia, hypertension, diabetes, coronary heart disease) , use of mechanical ventilation, prevalence of shock, infection, MODS, abdominal bleeding, ARDS, and ACS, long stay in the ICU may be risk factors for AKI in SAP. Clinical medical workers should early identify and intervene SAP patients with the above-mentioned risks, so as to reduce the incidence of AKI.

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24. Moxibustion on Governor Vessel Acupoints Improves the Cognitive Function and TCM Symptoms in Patients with Post-stroke Mild Cognitive Impairment Due to Deficiency of Kidney Essence
Yan WANG, Yanjie BAI, Ming ZHANG, Xiaoxiao LI, Yongchuang ZHANG
Chinese General Practice    2022, 25 (12): 1487-1492,F01.   DOI: 10.12114/j.issn.1007-9572.2021.02.113
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Background

Post-stroke mild cognitive impairment (PSMCI) is a common complication after stroke, which negatively affects patients' full recovery from stroke and imposes financial and emotional pressure on their families.

Objective

To observe the clinical efficacy of moxibustion on Governor vessel on the cognitive function and TCM syndromes in PSMCI due to deficiency of kidney essence.

Methods

Eligible patients with PSMCI (n=60) who were treated in Rehabilitation Center, the First Affiliated Hospital of Henan University of CM from July 2020 to July 2021 were selected, and evenly randomized to a control group (routine basic treatment plus routine cognitive rehabilitation training) and a moxibustion group 〔routine basic treatment plus routine cognitive rehabilitation training and moxibustion on the Governor vessel acupoints (once daily, five times per week) 〕, received four consecutive weeks of treatment. The Mini-Mental State Examination (MMSE) , and Montreal Cognitive Assessment (MoCA) were used to assess the cognitive function. Symptoms of kidney essence deficiency was assessed by the Scale for the Differentiation of Syndromes of Vascular Dementia (SDSVD) . And quality of life was measured by the Specifications for Stroke-Quality of Life (SS-QOL) . The overall clinical efficacy and safety of the two treatments were evaluated.

Results

Pre- and post-treatment comparisons of scores of MMSE and MoCA, SDSVD, and SS-QOL revealed that moxibustion group patients group had greater improvements in cognitive function, symptoms of kidney essence deficiency, and quality of life than control group patients (P<0.05) . Moreover, moxibustion group patients had better clinical outcomes (P<0.05) . The safety of treatment showed no significant intergroup differences (P>0.05) .

Conclusion

Moxibustion of the Governor vessel helps to better improve the cognitive function and TCM symptoms of PSMCI patients due to deficiency of kidney essence with good clinical efficacy and safety.

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25. Influencing Factors of Anemia in Patients with Diabetic Kidney Disease
Shili SHANG, Zijuan SUN, Lina BI, Wenjing ZHOU, Daiyu SHEN, Jingshan CHEN, Sha LUO, Yuerong FENG, Qian YANG, Jun LI
Chinese General Practice    2022, 25 (12): 1464-1469.   DOI: 10.12114/j.issn.1007-9572.2021.02.108
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Background

Patients with diabetic kidney disease (DKD) are more prone to anemia than those with non-diabetic kidney disease. Anemia quickens the progression of DKD, and is closely associated with cardiovascular disease and other complications. So studying the influencing factors of anemia in DKD is of great importance to the reduction of anemia incidence and the delaying of DKD progression.

Objective

To investigate the influencing factors of anemia in DKD.

Methods

Two hundred and fifty-four inpatients with DKD were selected from Department of Nephrology, First Affiliated Hospital of Kunming Medical University from January 2019 to September 2020. Data of them were retrospectively collected, including demographic information 〔gender, age, height, weight, blood pressure, duration of diabetes, calculated body mass index (BMI) , and smoke prevalence〕, and laboratory test indices 〔red blood cells (RBC) , serum hemoglobin (Hb) , total protein (TP) , albumin (ALB) , globulin (GLB) , alkaline phosphatase (ALP) , cholinesterase (CHE) , uric acid (SUA) , blood urea nitrogen (BUN) , creatinine (Scr) , cystatin C (Cys C) , retinol binding protein (RBP) , fasting plasma glucose (FPG) , calcium (Ca) , phosphorus (P) , magnesium (Mg) , zinc (Zn) , iron, unsaturatediron binding capacity (UIBC) , total iron binding capacity (TIBC) , ferritin, transferrin (TRF) , C-reactive protein (CRP) , and erythrocyte sedimentation rate (ESR) , glycated hemoglobin (HbA1c) , UALB/CRE, 24-hour urine for microalbumin (24 h-mALB) , 24-hour urine for total protein (24 h-MTP) 〕 and estimated glomerular filtration rate (eGFR) . One hundred and sixteen cases were diagnosed with anemia, and 138 without (anemia was defined as serum Hb≤130 g/L for men, and ≤120 g/L for women) . Spearman rank correlation analysis and multiple linear regression analysis were used to explore the factors associated with anemia in DKD.

Results

Compared with patients without anemia, those with anemia had higher systolic blood pressure, and longer duration of diabetes (P<0.05) . Moreover, anemia patients had lower levels of RBC, Hb, TP, ALB, GLB, CHE, eGFR, serum Ca, Zn, iron, UIBC, TIBC, ferritin, and TRF, and higher levels of BUN, Scr, Cys C, RBP, FPG, serum P, Mg, CRP, ESR, and HbA1c, UALB/CRE, 24 h-mALB, as well as 24 h-MTP (P<0.05) . Spearman rank correlation analysis showed that Hb was positively correlated with TP, ALB, CHE, eGFR, FPG, serum Zn, and iron, UIBC, TIBC, and ESR (P<0.05) and negatively correlated with SBP, duration of diabetes, BUN, Scr, serum Cys C, P, CRP, HbA1c, UALB/CRE, 24 h-mALB, and 24 h-MTP (P<0.05) . Multiple linear regression analysis showed that duration of diabetes (β=-0.060) , ALB (β=0.755) , CHE (β=1.512) , Zn (β=1.173) , and HbA1c (β=-5.766) in serum, and eGFR (β=0.341) were independently associated with serum Hb in DKD (P<0.05) .

Conclusion

Anemia in DKD may be associated with the duration of diabetes, serum levels of ALB, CHE, Zn and HbA1c, as well as eGFR. The above-mentioned influencing factors should be actively corrected to reduce the incidence of anemia and to improve the quality of life in DKD patients.

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26. Effect of Accurate Hierarchical Diagnosis and Treatment for Special Diseases: a Case Study of Chronic Kidney Disease
ZHU Haiyan, WANG Chaoxin, SUN Wanju
Chinese General Practice    2023, 26 (06): 749-753.   DOI: 10.12114/j.issn.1007-9572.2022.0643
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As an important measure to improve the supply of essential health services, the implementation of hierarchical medical system has encountered obstacles in different regions. Due to different referral standards in hospitals, temporal and geographical factors during treatment, it is difficult to promote the development of regional medical consortiums. Shanghai Pudong New Area People's Hospital, together with seven community health centers, established a Chuansha Medical Consortium, specifically for treating chronic kidney disease (CKD), using an accurate hierarchical management program for CKD supported by information technology, a hierarchical diagnosis and treatment system designed based on CKD management programs recommended by relevant guidelines, a CKD knowledge base in which medical information and referral criteria are incorporated, and a joint management model integrating hospital and community care. Empirical evaluation indicated that the hierarchical diagnosis and treatment model based on a CKD knowledge base could greatly contributed to accurately identifying vulnerable and high-risk population of CKD, timely screening and assessing patients with early stage CKD, and improving the efficiency of health management and diagnosis and treatment.

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27. Advances in Diagnosis and Management of Acute Kidney Injury Induced by Crush Syndrome
Jinxiang WANG, Yuxin DONG, Yibo ZHAO, Xianglong MENG, Yanfen CHAI, Heng JIN
Chinese General Practice    2022, 25 (15): 1914-1918.   DOI: 10.12114/j.issn.1007-9572.2021.02.132
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Crush syndrome (CS) often occurs in victims of natural disasters, trauma and traffic accidents, which mainly manifests as hypovolemic shock, acute kidney injury (AKI) , hyperkalemia, and acidosis, among which AKI is a major cause of the continuing high mortality of CS. Current treatments for AKI induced by CS include early rehydration, symptomatic treatment and renal replacement therapy, but the effects are not satisfactory. There are no standard treatment options for CS-related AKI, so identifying the pathogenesis of this disease and formulating an effective treatment regimen may be problems need to be solved urgently. This article reviews the latest advances in pathogenesis and treatment strategies of CS-related AKI.

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28. Development and Validation of a Risk Prediction Model of Post-stroke Acute Kidney Injury
Yan RAO, Meiqi YAO, Dawei JIANG, Cui MAO
Chinese General Practice    2022, 25 (23): 2885-2891.   DOI: 10.12114/j.issn.1007-9572.2022.0246
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Background

Acute kidney injury (AKI) is a common and serious complication that is closely correlated to a poor short-term or long-term prognosis in stroke patients. Therefore, it is necessary to develop a specific AKI screening tool to early identify patients at high risk of AKI.

Objective

To construct and verify a risk prediction model of post-stroke AKI and to develop a simple post-stroke AKI risk assessment scale.

Methods

Stroke inpatients with complete medical records were selected from the Second Affiliated Hospital Zhejiang University School of Medicine by use of convenience sampling, including 760 from neurology department treated during January to September 2021 (model group, 140 with AKI, and 620 without), and 310 treated during October to December 2021 (validation group, 53 with AKI and 257 without). Multivariate Logistic regression was used to identify factors associated with post-stroke AKI, then these factors were used to develop a risk prediction model. The Hosmer-Lemeshow test and receiver operating characteristic analysis were performed to assess the accuracy of fit and prediction value of the model, respectively. Then the model was verified in validation group, and based on the validation results, a simple post-stroke AKI risk assessment scale was developed.

Results

The prevalence of post-stroke AKI in the model group was 18.42% (P<0.05). Multivariate Logistic regression analysis showed that sex, history of hypertension, NIHSS score, history of use of loop diuretics, history of mechanical thrombectomy, serum levels of β2-MG, urea nitrogen, and sCysC were independently associated with post-stroke AKI (P<0.05). The post-stroke AKI risk prediction model constructed is y=1/ (1+e-a), in which a=-4.047+1.222× male + 1.386 × hypertension history + 1.716 × NIHSS score + 1.098 ×history of use of loop diuretics + 0.830 × mechanical thrombectomy history + 1.739 × β2-MG+1.202 × urea nitrogen + 2.160 × sCysC. The fit of the model was χ2=6.523, P=0.367. The AUC of the model for predicting post-stroke AKI in model group was 0.916 〔95%CI (0.891, 0.940) 〕, with 0.857 sensitivity, 0.832 specificity, and 0.689 Youden index when the optimal cut-off value was chosen as 12.8%. And the AUC of the model in predicting post-stroke AKI in the verification group was 0.906 〔95%CI (0.853, 0.960) 〕. The coefficients (β) derived from multivariate Logistic regression were rounded to the nearest integral value and weighted, then used to compile a simple scale with a total points of 11, whose AUC in predicting post-stroke AKI risk was 0.900〔95%CI (0.843, 0.957), P<0.001〕when the optimal cut-off value was determined as 4, and the accuracy rate of which in practical applications was 88.39%.

Conclusion

Our risk prediction model could effectively predict the risk of post-stroke AKI with high sensitivity and specificity, and the risk assessment scale compiled based on the model is a simple, feasible, objective, and quantitative tool for identifying high-risk patients, and the assessment result may be a reference for doctors and nurses to take interventions to early prevent AKI in stroke patients.

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29. Effectiveness and Safety of Roxadustat for Renal Anemia in Dialysis-dependent Chronic Kidney Disease: a Meta-analysis
LI Jiaqing, YANG Qing, YUAN Dunlu, HUANG Jingjing, CHANG Qing, NIE Jingwen, ZHOU Zhu, LI Qing
Chinese General Practice    2023, 26 (06): 704-710.   DOI: 10.12114/j.issn.1007-9572.2022.0581
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Background

As the most common clinical manifestation and a major complication in chronic kidney disease, anemia affects the patients' quality of life, increases the risk of renal disease progression and death. Hence, it is important to improve anemia, and monitor and evaluate drug efficacy and safety in the treatment of renal anemia.

Objective

To compare the efficacy and safety between roxadustat and erythropoiesis stimulating agents (ESAs) in treating renal anemia in patients with dialysis-dependent chronic kidney disease.

Methods

We searched PubMed, FMRS, Wanfang Data and ClinicalTrials.gov from inception to January 19, 2022 for randomized controlled trials (RCTs) about maintenance hemodialysis patients with dialysis duraion≥3 months treated with oral roxadustat (experimental group), versus injection of ESAs (control group). Two researchers independently conducted literature screening, data extraction and quality evaluation. Meta-analysis was performed using Review Manager 5.3.

Results

A total of 5 studies with 6 RCTs were included, involving 901 patients (549 in the experimental group and 352 in the control group). Meta-analysis showed that roxadustat was superior to ESAs in improving the levels of serum iron〔MD=2.49, 95%CI (0.82, 4.16), P=0.004〕, transferrin〔MD=0.31, 95%CI (0.17, 0.44), P<0.000 01〕, total iron-binding capacity〔MD=7.51, 95%CI (5.01, 10.01), P<0.000 01〕. The incidence of adverse events did not differ significantly between the two groups〔RR=1.10, 95%CI (0.99, 1.22), P=0.07〕.

Conclusion

Roxadustat demonstrates better effects than ESAs in increasing the levels of serum iron, transferrin and total iron-binding capacity, without increasing the risk of adverse events during a short-term duration of use.

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30. Diagnostic Value of Semi-quantitative Analysis of Microscopic Images of Masson's Trichrome-stained Histological Sections in Renal Interstitial Fibrosis 
WANG Wentao,LI Yan,HUANG Ting,ZHANG Yali
Chinese General Practice    2020, 23 (33): 4202-4208.   DOI: 10.12114/j.issn.1007-9572.2020.00.394
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Background Renal interstitial fibrosis(RIF) is a common pathway and the main pathological basis for the development of chronic kidney disease to end-stage renal disease.It is an important factor affecting the prognosis of patients with kidney disease.Early diagnosis and timely treatment are helpful to improve the prognosis.In recent years,many studies have found that RIF can be evaluated by cytokine and other biochemical indices,and ultrasound elastography and other non-invasive tests.However,due to cumbersome operation and high cost,such detections are difficult to be used widely in clinical practice.At present,RIF is manly diagnosed by pathological examination of percutaneous renal biopsy specimens using Masson's trichrome staining or other special staining techniques.But routine pathological diagnosis is made based on the pathologist's electronic microscopic observation of renal interstitial change,which may has subjective error,while diagnosis made using computer aided technology may be an automatic and objective analysis.So we performed a semi-quantitative analysis of microscopic images of the Masson's Trichrome-stained histological sections of RIF.Objective To assess the diagnostic value of Image-Pro Plus 6.0 in RIF based on this software measured integrated optical density as well as calculated mean optical density (MOD) of Masson's Trichrome-stained histological sections of RIF.Methods During January to September 2016,from Department of Nephrology,First Affiliated Hospital of Xi'an Jiaotong University,149 cases diagnosed with chronic interstitial nephritis (CIN) and chronic glomerular diseases(RIF group) were enrolled,and by the results of pathological examination of renal biopsy specimens,they were divided into CIN subgroup(including those with a diagnosis of tubulointerstitial nephritis with or without mesangial proliferative glomerulonephritis,n=26) and chronic glomerular disease (CGD) subgroup〔n=123,consisting of IgA nephropathy(n=79)(IgAN Ⅱ-Ⅴby LEE's glomerular grading with 3,35,25,16,respectively);including IgAN with different degrees of chronic glomerulonephritis hardening(n=44),that is,focal or proliferative sclerosing glomerulonephritis(n=31),or sclerosing glomerulonephritis(n=10),and chronic glomerulonephritis(n=3)〕.They were compared with 27 cases of stageⅠ-Ⅱmembranous nephropathy without RIF confirmed by the same pathological examination in our hospital.Correlations of MOD with clinical indicators 〔serum urea nitrogen (BUN),serum creatinine (Scr),cystatin C,hemoglobin (Hb),and serum and urine β2 microglobulin(β2-MG)〕 were analyzed.ROC analysis of MOD in the diagnosis of RIF was performed,with the optimal cutoff value,sensitivity and specificity were determined.Results In RIF group,MOD was positively correlated with Scr,serum and urine β2-MG,and was negatively correlated with Hb (P<0.05).In CGD subgroup,MOD was positively correlated with cystatin C,serum and urine β2-MG,and negatively correlated with Hb (P<0.05).In the diagnosis of RIF,the AUC of MOD was 0.982〔95%CI(0.961,1.000)〕 when the optimal cutoff value was determined as 0.012 3,with 0.886 sensitivity and 0.963 specificity in RIF group.In CIN subgroup,its AUC was 0.991〔95%CI(0.975,1.000)〕when the optimal cutoff value was determined as 0.011 8,with 1.000 sensitivity and 0.926 specificity.And in CGD subgroup,its AUC was 0.980〔95%CI(0.958,1.000)〕when the optimal cutoff value was determined as 0.008 0,with 0.992 sensitivity and 0.852 specificity.Conclusion MOD may reflect the degree of RIF,and the estimated optimal cut-off value of diagnosis may be to be 0.012 3.Moreover,it showed high sensitivity and specificity in diagnosing different types of RIF.
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31. The Analysis of Clinicopathological Characters and Short-term Prognosis in Idiopathic Membranous Nephropathy Patients with Immunoglobulin G4 Combined with Other Different Immunoglobulin G Subtypes Deposition
SUN Shuaigang, SHENG Xiaoxiao, ZHANG Wenhui, TIAN Huijuan, ZHAI Yaling
Chinese General Practice    2023, 26 (21): 2632-2638.   DOI: 10.12114/j.issn.1007-9572.2022.0847
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Background

The immunoglobulin (Ig) G subtype deposited pathologically in patients with idiopathic membranous nephropathy (IMN) is mainly IgG4, and the deposition of IgG1, IgG2 and IgG3 can also be detected. At present, there has been no report on the damage effect of different IgG subtypes in IMN on the pathological of kidney.

Objective

The purpose of the study was to investigate the clinicopathological characters and short-term prognosis in IMN patients with IgG4 combined with other different IgG subtypes deposition.

Methods

604 patients diagnosed with IMN in the First Affiliated Hospital of Zhengzhou University from January 2015 to June 2018 were included in the study, the baseline information, pathological test results of renal tissue specimens and treatment protocols of the patients were collected. According to the test results of IgG subtypes in renal pathology, the patients were divided into the simple IgG4 deposition group (n=259) , IgG4 combined with IgG1 deposition group (n=259) , IgG4 combined with IgG2 deposition group (n=29) , and IgG4 combined with IgG3 deposition group (n=57) . Starting from the date of percutaneous renal biopsy, the follow-up was performed until 2018-11-06. Kaplan-Meier survival curves of patients with different IgG subtypes were plotted, Log-rank test was used for survival curve comparison.

Results

24-h urine protein in IgG4 combined with IgG1 deposition group was higher than that in the simple IgG4 deposition group (P<0.05) ; the white blood cell count, neutrophil count, monocyte count and 24-h urine protein in the IgG4 combined with IgG3 deposition group were higher than those in the simple IgG4 group (P<0.05) . The positive deposition rates of C3, C4 and λ in the IgG4 combined with IgG1 deposition group were higher than those in the simple IgG4 deposition group (P<0.05) ; the positive deposition rate of C3 in the IgG4 combined with IgG2 deposition group was higher than that in the simple IgG4 deposition group (P<0.05) ; the positive deposition rates of C3, C4 and C1q, semi-quantitative scores of renal tubular atrophy and renal interstitial fibrosis were significantly different between the IgG4 combined with IgG3 deposition group and the simple IgG4 deposition group (P<0.05) . Log-rank test results showed no significant difference in cumulative response rates among the four groups (χ2=0.684, P=0.408) .

Conclusion

The renal clinical and pathological changes were more serious in IgG4 combined with other different IgG subtypes patients than those with IgG4 alone, patients with IgG3 deposition had a more prominent clinicopathological phenotype. There was no significant difference in remission rate after 6 months of follow-up, which may be related to the different intensity of inflammatory response caused by different capacities to fix complement of different IgG subtypes.

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32. The Value of Simplified Calculation of CT Enhanced Washout Rate in Distinguishing Adrenal Metastasis and Adrenal Adenoma Less Than 4 cm 
DAI Guojiao,ZHENG Hailan,ZHENG Yongfei,HUANG Danjiang
Chinese General Practice    2021, 24 (20): 2607-2613.   DOI: 10.12114/j.issn.1007-9572.2021.00.571
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Background Among incidental adrenal tumors,adrenal metastases need to be distinguished from the most common benign adrenal tumors (adrenal adenomas).It is recommended to delay the scan for 15 minutes to calculate the absolute percentage washout and relative percentage washout,but the scanning time is too long.Objective To explore the value of simplified calculation of CT enhanced washout rate in distinguishing adrenal metastases and adrenal adenomas less than 4 cm.Methods 78 patients with adrenal metastasis and 50 patients with adrenal adenoma who were confirmed by clinical follow-up or suspected to be diagnosed as non-adrenal adenoma lesions followed by surgical pathology and enhanced CT scanning in Taizhou First People's Hospital from January 2014 to December 2019 were selected.According to the inclusion and exclusion criteria,37 patients with adrenal metastasis(adrenal metastasis group) and 47 patients with adrenal adenoma (adrenal adenoma group) were finally included in this study;among them,patients with adrenal metastases included 16 patients with lung cancer as the primary tumor and 21 patients with other tumors as the primary tumor (4 patients with liver cancer,14 patients with gastrointestinal cancer,1 patient with pancreatic cancer,1 patient with bladder cancer,1 patient with salivary gland cancer),and patients with adrenal adenomas included 15 patients with lipid-poor adrenal adenoma and 32 patients with lipid-rich adrenal adenoma.The age,sex,occurrence of hypertension,lesion location (left/right) and tumor size of patients were collected and CT attenuation value of plain scan,arterial phase and portal venous phases were measured to calculate simplified absolute percentage washout and relative percentage washout.Receiver operating characteristic curves (ROC) were used to assess the efficacy of statistically significant variables between groups including adrenal metastasis and adrenal adenoma groups,adrenal metastasis and lipid-poor adrenal adenoma groups,adrenal metastasis and lipid-rich adrenal adenoma groups,adrenal metastasis of lung cancer and lipid-poor adrenal adenoma groups respectively.Results There were no statistical differences in age,gender,occurrence of hypertension,and the location and size of lesions between groups including adrenal metastasis and adrenal adenoma groups,adrenal metastasis and lipid-poor adrenal adenoma groups,adrenal metastasis and lipid-rich adrenal adenoma groups,adrenal metastasis of lung cancer and lipid-poor adrenal adenoma groups(P>0.05).The plain CT value of patients in the adrenal metastasis group was higher than the adrenal adenoma group (P<0.001).The plain CT value of patients in the adrenal metastasis group was higher than the lipid-poor adrenal adenoma group and the absolute percentage washout and relative percentage washout of patients in the adrenal metastasis group was lower than the lipid-poor adrenal adenoma group (P<0.05).The plain CT value and relative percentage washout of patients in the adrenal metastasis group were higher than the lipid-rich adrenal adenoma group(P<0.05) and there was no significant difference in the absolute percentage washout between the adrenal metastasis group and the lipid-rich adrenal adenoma group (P>0.05).The plain CT value of patients in the lung cancer adrenal metastasis group was higher than the lipid-poor adrenal adenoma group,and the absolute percentage washout and relative percentage washout of patients in lung cancer adrenal metastasis group were lower than the lipid-poor adrenal adenoma group (P<0.05).In the ROC curve analysis of adrenal metastasis and adrenal adenoma,the cut-off value of plain CT value was 21.00 HU,and the AUC,sensitivity,and specificity were 0.894,81.1%,and 89.4%,respectively.In the ROC curve analysis of adrenal metastasis and lipid-poor adrenal adenoma,the cut-off value of plain CT value was 28.50 HU,and the AUC,sensitivity,and specificity were 0.746,64.9%,and 86.7%,respectively.The cut-off value of the absolute percentage washout was -21.54%,and the AUC,sensitivity,and specificity were 0.733,80.0%,and 83.8%,respectively.The cut-off value for the relative percentage washout was -9.65%,and the AUC,sensitivity,and specificity were 0.760,73.3%,and 89.2%,respectively.In the ROC curve analysis of adrenal metastasis and lipid-rich adrenal adenoma,the cut-off value of plain CT value was 11.50 HU,and the AUC,sensitivity and specificity were 0.964,91.9% and 100.0%,respectively.The cut-off value of the relative percentage washout was -64.10%,and the AUC,sensitivity and specificity were 0.677,89.2% and 53.1%,respectively.In the ROC curve analysis of lung cancer adrenal metastasis and lipid-poor adrenal adenoma,the cut-off value of plain CT value was 29.50 HU,and the AUC,sensitivity,and specificity were 0.881,81.3%,and 93.3%,respectively.The cut-off value of the absolute percentage washout was -24.89%,the AUC,sensitivity,and specificity were 0.721,80.0%,and 81.3%,respectively.The cut-off value for relative percentage washout was -10.58%,the AUC,sensitivity,and specificity were 0.733,73.3%,and 87.5%,respectively.Conclusion  Simplified calculation of CT enhanced absolute percentage washout and relative percentage washout is of great value in distinguishing adrenal metastases and adrenal adenomas less than 4 cm.
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33. Clinical Features and Associated Factors of Asymptomatic Nephrolithiasis/Nephrocalcinosis in Primary Aldosteronism
Xu CAO, Xianjun ZHU, Yan YANG, Nie TANG, Limei LIU, Hui ZHOU, Lei ZHANG, Ying ZHU, Yi YANG, Wei XIA, Youren LIU
Chinese General Practice    2022, 25 (21): 2635-2639.   DOI: 10.12114/j.issn.1007-9572.2022.0232
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Background

Urinary calculi in primary aldosteronism (PA) have been studied almost only in case reports, and most of which have been reported to be associated with nephrolithiasis. Literature review demonstrates that there are few reports on the prevalence, clinical characteristics and possible causative factors of asymptomatic nephrolithiasis/nephrocalcinosis in PA.

Objective

To investigate clinical features and possible causative factors of asymptomatic nephrolithiasis/nephrocalcinosis in primary aldosteronism patients in Sichuan.

Methods

In this retrospective study, we enrolled 147 PA patients from Department of Endocrinology, Sichuan Provincial People's Hospital from January 2017 to April 2021, including 34 also with asymptomatic nephrolithiasis/nephrocalcinosis and 113 patients with PA alone. Clinical data were collected, including sex, age, duration of hypertension, duration of hypokalemia, the lowest serum potassium level in medical history, abnormal glucose metabolism, smoking history, drinking history, systolic blood pressure at admission, diastolic blood pressure at admission, body mass index, waist circumference, estimated glomerular filtration rate (eGFR) , fasting blood glucose, serum uric acid, total protein, albumin, potassium, sodium, calcium, magnesium, phosphorus, carbon dioxide, pH value, bicarbonate (HCO3) , total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein, and glycated hemoglobin, plasma aldosterone concentration, direct renin concentration, and aldosterone-renin ratio in upright posture, serum 25 hydroxyvitamin D, and parathyroid hormone (PTH) , 24-hour urinary electrolyte excretion (K, Na, Ca, Mg, P) , urine microalbumin to creatinine ratio, and urinary pH value. Binary Logistic regression analysis was used to explore the independent risk factors of asymptomatic nephrolithiasis/nephrocalcinosis in PA.

Results

Compared with patients with PA alone, those also with asymptomatic nephrolithiasis/nephrocalcinosis had higher proportion of males, previous or current smokers, and previous or current drinkers, higher mean levels of serum pH value, HCO3 and PTH, longer mean duration of hypertension, as well as lower eGFR (P<0.05) . Binary Logistic regression analysis showed that serum PTH level〔OR=1.009, 95%CI (1.001, 1.017) , P=0.034〕 was associated with asymptomatic nephrolithiasis/nephrocalcinosis in PA.

Conclusion

Clinical features manifested by PA patients with asymptomatic nephrolithiasis/nephrocalcinosis are as follows: male predominate, longer duration of hypertension, higher rates of smoking and alcohol consumption, and higher serum pH, HCO3 and PTH levels. Elevated serum PTH level or secondary hyperparathyroidism may be associated with increased risk of asymptomatic nephrolithiasis/nephrocalcinosis in PA.

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34. Clinical Interpretation of Physical Activity and Exercise in Peritoneal Dialysis: International Society for Peritoneal Dialysis and the Global Renal Exercise Network Practice Recommendations
YANG Changyuan, LING Xitao, HU Xiaoxuan, ZHANG La, QIN Xindong, LIU Hui, LU Fuhua, SU Guobin
Chinese General Practice    2023, 26 (09): 1031-1037.   DOI: 10.12114/j.issn.1007-9572.2022.0713
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Peritoneal dialysis (PD) patients generally have low level of physical activity and poor physical functions. Maintaining good physical function has always been a health concern of PD patients. However, there has been no consensus on how to carry out physical activity/exercise intervention and to maintain good physical function in PD patients. Practice recommendations of Physical Activity and Exercise in Peritoneal Dialysis (hereinafter referred to as PAEPD) , the first global practice recommendations on physical activity and exercise in PD patients, were released by International Society for Peritoneal Dialysis (ISPD) and the Global Renal Exercise Network (GREX) in February 2022. In accordance with the physical activity and exercise in Chinese PD patients, after reviewing the PAEPD and other relevant international recommendations, we performed a clinical interpretation of PAEPD in detail, towards addressing the concerns of clinical healthcare workers and PD patients in China: timing of exercise and activity, and volume of intraabdominal fluid recommended during physical activity, core strengthening, potential symptoms and adverse events related to activity and exercise, and individualized activity and exercise. All this will provide clinical healthcare workers with guidance on the management of physical activity and exercise in PD patients.

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35. Clinical,endothelial,hemorheological and immune responses in patients with early diabetic nephropathy to the treatment with Compound Xiancao Granules(a Zhuang Medicine)
HUANG Yalan1,HUANG Guodong2*,CAI Linkun1,HUANG Qionghe1,GAN Jiali1,XUE Hanyu1
Chinese General Practice    2020, 23 (24): 3086-3093.   DOI: 10.12114/j.issn.1007-9572.2020.00.243
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Background At present,the application of Western medicine treatment alone is not very effective in patients with early diabetic nephropathy(DN),especially in microcirculation disturbance,abnormal endothelial function,hemorheology and immune function.Moreover,after such treatment,the disease is easily recur.Therefore,it is particularly important to find a more effective treatment for early DN.Objective To explore the clinical,endothelial,hemorheological and immune responses in patients with early DN to the treatment with Compound Xiancao Granules,a Zhuang Medicine.Methods From July 2018 to April 2019,60 patients with early DN were selected from Department of Nephrology,Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine and were randomly and equally divided into control group and observation group.Both groups were treated with routine treatment combined with intravenous administration of alprostadil injection,the observation group additionally orally administered Compound Xiancao Granules.The treatment course lasted for 4 weeks.Clinical response,renal function parameters〔24 h urinary albumin excretion rate(UAER),serum creatinine(Scr) and cystatin C(Cys C)〕,microcirculation and endothelial function parameters 〔thromboxane-B2(TX-B2),nitric oxide(NO),endothelin-1(ET-1),von Willebrand factor(vWF) and thrombomodulin(TM)〕,whole blood viscosity at high shear rates(ηbH),whole blood viscosity at medium shear rates(ηbM),whole blood viscosity at low shear rates(ηbL),plasma viscosity(ηp),fibrinogen(FIB),and erythrocyte aggregation index(AI),and immune parameters〔CD4+ helper T cells,CD8+ T suppressor cells,and CD4+/CD8+ 〕 were compared between the two groups before and after treatment.Results The overall clinical response of the observation group was better than that of the control group(P< 0.05).After treatment,the mean levels of UAER,Scr,Cys C and TX-B2 of the observation group were significantly lower than those of the control group(P<0.05).The observation group showed higher NO but lower mean ET-1,vWF and TM compared with the control group(P<0.05).Moreover,mean post-treatment ηbH,ηbM,ηbL,ηp,FIB and erythrocyte AI of the observation group were significantly lower than those of the control group(P<0.05).Furthermore,the observation group showed higher mean CD4+ and CD4+/CD8+ but lower mean CD8+ after treatment(P<0.05).Conclusion Compound Xiancao Granules in combination with Western medicine achieves good response in treating deficiency of spleen and kidney,and damp-heat and blood stasis syndrome in early DN patients,mainly manifesting as alleviating the microcirculation disturbance,improving renal,endothelial,hemorheological and immune functions.
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36. Intestinal Flora in Children with Henoch-Schönlein Purpura Nephritis: Composition and Abundance Analysis and Clinical Significance
ZHANG Li, ZHANG Jianjiang, DOU Wenjie, ZENG Huiqin, WANG Qin
Chinese General Practice    2023, 26 (18): 2250-2255.   DOI: 10.12114/j.issn.1007-9572.2022.0656
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Background

The number of studies about the status of intestinal flora in children with Henoch-Sch?nlein purpura (HSP) is limited, and there are no reports on changes of intestinal flora in children with Henoch-Sch?nlein purpura nephritis (HSPN) at the early stage of the disease.

Objective

To investigate the changes of intestinal flora in HSPN children and their association with the development of the disease.

Methods

Thirty-seven newly treated children with HSP (test group) were selected from Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University from July to September 2019, and compared to 12 healthy children (control group) in terms of the status of intestinal flora. The test group was further divided into non-renal injury subgroup (13 cases) and renal injury subgroup (24 cases) according to the prevalence of renal injury during a 6-month follow-up. General data and stool specimens were collected from the affected children and healthy children. High-throughput sequencing was used to sequence and analyze the intestinal flora of all subjects. Alpha diversity (Shannon index, Chao1 index, ACE index) analysis was used to explore the richness and diversity of the microbial communities within the samples. Principal coordinate analysis (PCoA) was used to explore the differences in community structure among the groups, linear discriminant analysis effect size (LEfSe) analysis were used to identify species with significant differences.

Results

Alpha diversity analysis results showed that there was no statistically significant difference in Shannon index, Chao1 index and ACE index among the three groups (P>0.05). PCoA showed that the composition of intestinal flora varied across renal injury and non-renal injury subgroups and the control group (P<0.05). Further Adonis analysis revealed that the intestinal flora composition varied significantly between non-renal injury subgroup and the control group (F=2.172, P=0.006), and between renal injury subgroup and the control group (F=2.217, P=0.006), as well as between renal injury and non-renal injury subgroups (F=1.590, P=0.045). LEfSe analysis showed, compared with the control group, the test group had significantly decreased abundance of Blautia, Chryseobacterium, Agathobacter and Roseburia (P<0.05), and significantly increased abundance of Megamonas and Enterococcus (P<0.05). Compared with non-renal injury subgroup, renal injury subgroup had significantly reduced abundance of Christensenella and Bacteroides (P<0.05), and significantly increased abundance of Lactobacillus and Rothia (P<0.05) .

Conclusion

Intestinal flora disorders were found in HSP children, the intestinal flora of children with HSPN at the early stage of the disease were different from those of HSP children without renal injury, suggesting that the intestinal flora disorder at the early stage of the disease may be closely related to the development of HSPN.

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37. Interpretation of the Major Updates of Guidelines Regarding Hyperuricemia and Gout in Chronic Kidney Disease 
WANG Xu,LUO Dongping,RU Yanhai,GUO Xiaokai,XU Jiayun
Chinese General Practice    2021, 24 (33): 4191-4195.   DOI: 10.12114/j.issn.1007-9572.2021.00.573
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The incidence of hyperuricemia(HUA)and gout is increasing significantly,and tends to occur at an early age with the social development and changes in patterns of life. HUA has become the second leading metabolic disease following diabetes mellitus,which is not only a common complication of chronic kidney disease(CKD),but also an important risk factor for CKD. The guidelines for the diagnosis and treatment of HUA and gout have been updated to accommodate newly emerging evidence. We interpreted the essentials of new updates regarding HUA and gout in CKD on the basis of research evidence,including the indication of initial urate-lowering therapy,selection of pharmacologic urate-lowering therapy,gout flare management,alkalinizing urine and use of vitamin C on the basis of research evidence,hoping to provide clinicians with supports for delivering comprehensive and individual therapies.
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38. Association of Blood Pressure Level with the Risk of Chronic Kidney Disease among the Elderly in Longevity Areas of China
ZHANG Yunsheng, ZHANG Peng, JIN Yujing, GAO Ying
Chinese General Practice    2023, 26 (28): 3502-3506.   DOI: 10.12114/j.issn.1007-9572.2022.0876
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Background

Chronic kidney disease (CKD) is a serious risk to the health and longevity of the elderly, and hypertension is closely related to CKD. However, the studies on the correlation of blood pressure levels with the development and progression of CKD in older adults have shown inconsistent results.

Objective

To explore the association between blood pressure levels and the risk of CKD among the elderly in longevity areas of China.

Methods

From October 2021 to May 2022, a total of 989 older adults who underwent physical examination with biomedical indicators collected in 2012 were selected as subjects based on the subcohort of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) -Healthy Aging and Biomarkers Cohort Study (HABCS) . Age, gender, height, weight, blood pressure, blood lipid, blood glucose, routine blood and urine indicators were collected at baseline, and follow-up monitoring was conducted in 2014. Cox proportional hazards regression model was used to analyze the association between the blood pressure levels and the risk of CKD.

Results

A total of 989 subjects were included in the study, with a median age of 79 (70, 88) years. The cumulative follow-up were 2 046 person-years, with an average follow-up time of (2.07±0.50) years. There were 183 new cases of CKD, the cumulative incidence of CKD was 18.5%〔95%CI (16.1%, 21.1%) 〕, and the incidence density was 89.4/1 000 person-years. During the follow-up, 9.8% (10/102) , 14.0% (47/335) and 22.8% (126/552) of the older adults in the normal blood pressure, high normal blood pressure and hypertension groups developed CKD, respectively, and the difference was statistically significant among the three groups (χ2=16.40, P<0.001) . The results of Cox regression showed that after adjusting for age, sex, BMI, waist circumference, calf circumference, fasting blood glucose, glycosylated serum protein, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, uric acid, superoxide dismutase, vitamind3, white blood cell count, red blood cell count, platelet count, blood urea nitrogen and history of diabetes, the older adults in the hypertension group had a higher risk of CKD〔HR (95%CI) =2.28 (1.13, 4.60) 〕 than those in the normal blood pressure group; the risk of CKD was 1.83 times〔95%CI (1.02, 3.29) 〕 higher in the older adults with baseline SBP≥140 mmHg (1 mmHg=0.133 kPa) than those with baseline SBP<120 mmHg, and the risk of CKD was 1.55 times〔95%CI (1.02, 2.35) 〕 higher in the older adults with baseline DBP≥90 mmHg than those with baseline DBP<80 mmHg (P<0.05) .

Conclusion

Hypertension is an independent risk factor for CKD in the elderly. It is particularly important to increase screening and prevention of CKD in older adults with predominantly elevated systolic blood pressure.

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39. Effect of Qingre Xiaozheng Formula on Improving Renal Injury in a Rat Model of Diabetic Kidney Disease
Yujie WANG, Jian WANG, Jingwei ZHOU
Chinese General Practice    2022, 25 (29): 3678-3685.   DOI: 10.12114/j.issn.1007-9572.2022.0357
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Background

Qingrexiaozheng formula (QRXZF) has been shown to be effective in improving kidney injury in diabetic kidney disease (DKD) , but the mechanism remains to be unclear.

Objective

To explore the effect and mechanism of action of QRXZF in the improvement of kidney injury induced by unilateral nephritic resection combined with streptozotocin (STZ) in DKD rats.

Methods

The experiment was implemented from July to November, 2019. Thirty healthy SPF male SD rats were randomly divided into sham operation group (NC group, n=10) and model group (n=20) . Rats in NC group received 1 cm transverse incision performed at the body surface anatomical position of the right kidney and sutured, and intraperitoneal injection of citric acid buffer when the wound healed one week later. Those in model group were treated with right nephrectomy, and received a single intraperitoneal injection of STZ solution (55 mg/kg) with the same volume as the citric acid buffer for the NC group one week later to establish the DKD model. Then rats in the model group were randomly divided into DKD subgroup (n=10) and QRXZF subgroup (n=10) when the modeling was successfully achieved. After this, rats in NC group and DKD subgroup received intragastric administration of the same amount (1 ml/100 g) of 0.9% sodium chloride solution once a day, and those in QRXZF subgroup received intragastric administration of QRXZF at a dose of 7.92 g·kg-1·d-1. During the intervention, weight was measured every week. After 16 weeks of intervention, a 24-hour urine, serum and kidney tissue specimens were collected, kidney weight was measured, and the kidney weight index was calculated. Enzyme-linked immunosorbent assay was used to detect the microalbumin in 24-hour urine (24 hUpro) . The automatic biochemical analyzer was used to analyze serum creatinine (Scr) , blood urea nitrogen (BUN) and serum albumin (ALB) . Hematoxylin-eosin staining, Periodic Acid-Schiff staining and Masson's trichrome staining were performed to observe the damage degree of kidney tissue. Immunohistochemical method was used to detect the expression level of Caspase-3 and p16 in kidney tissue. The apoptosis of renal tubular cells was detected by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling.

Results

Compared with rats in the NC group, those in DKD and QRXZF subgroups had lower weight and higher kidney weight index (P<0.01) . Rats in QRXZF subgroup had higher weight and lower kidney weight index than those in DKD subgroup (P<0.01) . In comparison to rats in the NC group, rats in DKD subgroup had higher levels of 24 hUpro, Scr and BUN lower level of ALB (P<0.01) , and those in QRXZF subgroup had higher levels of 24 hUpro and BUN, and lower level of ALB (P<0.01) . Rats in QRXZF subgroup had higher levels of 24 hUpro, Scr and BUN, and lower level of ALB than did those in DKD subgroup (P<0.01) . Compared with rats in the NC group, obvious pathological injury, glomerular hypertrophy and interstitial tubular fibrosis were observed in kidney tissues in rats of both DKD and QRXZF subgroups, but the degree of pathological changes was much lighter in QRXZF subgroup. Immunohistochemistry analysis showed that the expression levels of P16 and Caspase-3 in renal tissue in DKD or QRXZF subgroup were higher than those in NC group (P<0.01) . The expression levels of P16 and Caspase-3 in renal tissue in QRXZF subgroup were lower than those in DKD subgroup (P<0.01) . The rate of renal tubular cell apoptosis in DKD or QRXZF subgroup was higher than that in NC group (P<0.01) . The rate of renal tubular cell apoptosis in QRXZF subgroup was lower than that in DKD subgroup (P<0.01) .

Conclusion

QRXZF effectively improved the renal function, attenuate the pathological damage and fibrosis of the kidney, inhibit the expression of Caspase-3 and p16 in renal tissues, and decrease the rate of renal tubular cell apoptosis in DKD rats, suggesting that the mechanism of QRXZF in improving kidney may be related to inhibiting the aging and apoptosis of kidney cells.

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40. Influence of Microbiota-modulating Agents on Gut Flora in Community Patients with Diabetic Nephropathy
SHEN Fei, JIANG Weiping, MEI Xiaobin, HAN Yiping, ZHAO Jiayi, FAN Jian, GU Juan, SHEN Yanhong, XU Hongmei, ZHANG Dan, MEN Ying, DING Haiguang, CHEN Caiping, HAN Junhua
Chinese General Practice    2023, 26 (09): 1112-1117.   DOI: 10.12114/j.issn.1007-9572.2022.0691
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Background

Imbalanced gut flora caused by changes in gut microecological structure and diversity plays an important role in the interaction between diabetes and chronic kidney disease. Rational application of probiotics, prebiotics and other microbiota-modulating agents is contributive to the improvement of gut microbial flora environment and chronic inflammation, as well as the delay of deterioration of renal function in patients with diabetic nephropathy (DN) .

Objective

To understand the effect of probiotics, a microbiota-modulating agent, administered based on gut flora status in patients with DN.

Methods

Participants were selected from Shanghai Yinhang Community Health Center by use of stratified random sampling in 2019, including 115 patients with DN were randomly divided into control group (57 with usual treatment) and treatment group (58 with treatment with microbiota-modulating agents) . Laboratory test indices and intestinal bacterial culture results were compared between the two groups after eight weeks of treatment to assess the effect of microbiota-modulating agents on improving gut flora in DN.

Results

Among 115 patients with DN, there were 28 males and 87 females, the mean age was (62.9±10.0) years, and the duration of diabetic nephropathy was (14.3±7.1) years. There were no significant differences in the proportion of males, mean age, body mass index, proportion of early DN, and duration of DN between DN patients with usual treatment and those with microbiota-modulating agents treatment (P>0.05) . Compared with DN patients with usual treatment, DN patients with microbiota-modulating agents treatment had decreased levels of glucose, triglyceride, blood urea nitrogen, serum creatinine, albumin to creatinine ratio, Cystatin C, C-reactive protein, interleukin-1β, and tumor necrosis factor-α, and increased levels of high-density lipoprotein and estimated glomerular filtration rate after treatment (P<0.05) . Moreover, DN patients with microbiota-modulating agents treatment showed lower numbers of Enterococcus (Z=16.482, P<0.001) and Enterobacter (Z=5.138, P<0.001) colonies, and higher numbers of Bifidobacterium (Z=2.470, P=0.014) , and Lactobacillus (Z=8.384, P<0.001) colonies after treatment.

Conclusion

The number of Enterococcus and Enterobacter colonies decreased and that of Bifidobacterium and Lactobacillus colonies increased in DN patients after treatment with microbiota-modulating agents, indicating that these agents could improve the gut flora.

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