Special Issue:Kidney Disease
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.
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.
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.
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.
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.
To investigate whether AF increases the risk of new-onset CKD in northern Chinese population.
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.
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〕.
AF is an independent risk factor for new-onset CKD in northern Chinese population, especially for young and middle-aged populationaged≤65 years.
Rosuvastatin calcium with metformin improves diabetic renal injury, but the mechanism is not yet fully understood.
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) .
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.
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) .
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.
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.
To explore the TCM-related factors and pathogenesis associated with MHT in IgAN patients.
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.
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.
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.
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.
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.
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.
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) .
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.
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.
To systematically evaluate the factors associated with CI in Chinese patients with ESRD.
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.
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.
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.
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.
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".
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.
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) .
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.
The incidence and prevalence of chronic kidney disease (CKD) remain high. Hypertension and diabetes frequently coexist and jointly accelerate the progression of kidney disease. The lipid accumulation product index (LAPI) is a novel indicator for predicting cardiovascular disease and abnormalities in glucose metabolism, and its relationship with CKD warrants further investigation.
This study aimed to investigate the relationship between LAPI and the risk of developing CKD in patients with hypertension and abnormal glucose metabolism.
A retrospective cohort of 2 033 patients with hypertension and abnormal glucose metabolism admitted to the Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region from January 2012 to May 2019 was enrolled. General patient information and laboratory test indicators were collected. The LAPI was calculated, and the population was divided into four groups based on LAPI quartiles: Q1 (LAPI≤44.03, n=509), Q2 (44.03<LAPI≤64.68, n=508), Q3 (64.68<LAPI≤98.90, n=508), and Q4 (LAPI>98.90, n=508). Patients were followed up, with the endpoint event being CKD. Kaplan-Meier curves were used to analyze the cumulative incidence of CKD at different LAPI levels, and the Log-rank test was used to compare differences. Multivariate Cox regression models were employed to analyze the relationship between LAPI and CKD. Restricted cubic splines were fitted to the multivariate Cox regression model to explore the dose-response relationship between LAPI and CKD. Subgroup analysis and sensitivity analysis were conducted to test the stability of the relationship between LAPI and CKD.
Significant differences were observed in age, gender, BMI, waist circumference, heart rate, diastolic blood pressure, smoking, alcohol consumption, uric acid, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, glycated hemoglobin, fasting blood glucose, use of calcium channel blockers, and hypoglycemic treatment among the 4 groups (P<0.05). Log-rank test results indicated that the cumulative risk of CKD increased with elevating LAPI levels (χ2=14.48, P<0.001). Multivariate Cox regression analysis revealed that for each standard deviation increase in LAPI, the hazard ratio (HR) for CKD increased by 12.5% (HR=1.125, 95%CI=1.035-1.223, P=0.005) ; compared to the Q1 group, the Q4 group had a 54.9% higher risk of CKD (HR=1.549, 95%CI=1.129-2.125, P=0.007). Restricted cubic spline regression analysis showed that LAPI>65.59 was a risk factor for CKD (P=0.007). Interaction and subgroup analyses revealed that the association between LAPI and the risk of developing CKD remained stable.
In patients with hypertension and abnormal glucose metabolism, a higher LAPI in the early stages increases the risk of developing CKD.
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.
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.
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.
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%.
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.
Hypertensive nephropathy, a common chronic kidney disease, is a significant contributor to end-stage renal disease. Analyzing and predicting its epidemiological trends is crucial for the prevention and control of chronic kidney disease.
This study aims to analyze the temporal trends in the incidence and mortality of hypertensive nephropathy in China from 1990 to 2021 and to provide a theoretical basis for developing prevention and control strategies.
Data on the incidence and mortality of hypertensive nephropathy in China were obtained from the Global Burden of Disease (GBD) 2021 database. Joinpoint regression models were used to analyze the average annual percentage change (AAPC) in incidence and mortality. Age-period-cohort models were applied to estimate the age, period, and cohort effects by gender. Bayesian age-period-cohort (BAPC) methods were employed to predict the standardized incidence and mortality rates for both genders from 2022 to 2032.
After age standardization, the age-standardized incidence rates (ASIR) for both males and females showed a slight decline from 1990 to 1995, followed by a gradual increase. The age-standardized mortality rate (ASMR) for males decreased from 5.44 per 100 000 in 1990 to 4.72 per 100 000 in 2021, while for females, it decreased from 3.86 per 100 000 to 2.75 per 100 000, with a more pronounced decline in females. Joinpoint regression analysis indicated an overall increasing trend in ASIR (AAPC for males: 0.43%, females: 0.64%, P<0.05). The fastest decline in male ASIR occurred from 1990 to 1992 (APC=-1.62%, P<0.05), while the fastest increase was from 2019 to 2021 (APC=1.30%, P<0.05). For females, the fastest decline in ASIR was from 1990 to 1995 (APC=-1.31%, P<0.05). Overall, the ASMR rate showed a decreasing trend (AAPC for males: -0.51%, females: -1.09%, P<0.05), with a more significant decline in females. The fastest decline in male ASMR was from 2004 to 2007 (APC=-3.26%, P<0.05), while the fastest increase was from 1998 to 2004 (APC=1.30%, P<0.05). For females, the fastest decline in ASMR was also from 2004 to 2007 (APC=-4.47%, P<0.05). Age-period-cohort analysis revealed that males generally had higher incidence and mortality rates than females across all age groups, with rates increasing with age. The incidence growth accelerated after age 60-65, and mortality growth accelerated after age 70. The period effect on incidence risk was slightly higher in females than in males, while the cohort effect showed an overall increasing trend in incidence and a decreasing trend in ASMR for both genders. Predictions from 2022 to 2032 indicate a continued rise in ASIR and a sustained decline in mortality for both genders.
From 1990 to 2021, the ASIR of hypertensive nephropathy in China showed an overall upward trend, while ASMR decreased. Both incidence and mortality increased with age, particularly in the elderly. Over the next decade, ASIR is expected to continue rising, while ASMR will decline slowly. These findings suggest a need to focus on male and elderly patients in developing targeted prevention and control measures.
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.
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.
To systematically analyze the risk factors of AKI in SAP.
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.
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.
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.
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.
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.
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.
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) .
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.
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.
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.
To construct and verify a risk prediction model of post-stroke AKI and to develop a simple post-stroke AKI risk assessment scale.
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.
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%.
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.
Parathyroid hormone type 1 receptor (PTH1R), a member of the G-protein-coupled receptor family, is extensively expressed in the human body and is involved in various processes such as embryonic development, calcium and phosphorus homeostasis, body metabolism and tumorigenesis. PTH1R is highly expressed in the kidney, and its activation is involved in the development and progression of renal diseases though multiple mechanisms and complicated pathways, and is closely associated with a variety of renal diseases such as diabetic nephropathy, glomerulonephritis, acute kidney injury, and chronic kidney disease. This article reviews recent studies about the function of PTH1R, and its role and mechanism of action in renal diseases, and provides an in-depth discussion on the relationship and related mechanisms between PTH1R and kidney diseases, offering new ideas for the diagnosis and treatment of kidney diseases.
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.
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.
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.
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) .
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.
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.
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.
To investigate the influencing factors of anemia in DKD.
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.
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) .
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.
Diabetic nephropathy (DN) is the common microvascular complication of diabetes mellitus, and also one of the main causes of end-stage renal disease. Renal biopsy is the gold standard for the pathological diagnosis of DN. Previous studies on traditional Chinese medicine (TCM) factors influencing DN lack the basis of renal biopsy, potentially leading to an inaccurate participant recruitment (selection bias) .
To investigate the distribution of TCM syndrome types in DN patients and the relevant TCM syndrome elements in those with massive proteinuria and renal insufficiency, thereby providing TCM research directions in the pathogenesis of DN.
From January 2022 to January 2024, TCM and clinical data of 78 patients diagnosed with type 2 diabetes mellitus (T2DM) with a confirmation of DN through renal biopsy in the Department of Nephrology of First Medical Center of Chinese PLA General Hospital were included. The distribution and clinical characteristics of TCM syndrome types were explored. Binary Logistic regression was employed to explore the TCM syndrome elements associated with massive proteinuria (24-hour urinary protein quantification>3.5 g) and estimated glomerular filtration rate (eGFR) <60 mL·min-1· (1.73 m2) -1 in DN patients.
According to the classification of chronic kidney disease (CKD), there were 11 cases in stageⅠgroup, 19 in stageⅡgroup, 22 in stageⅢgroup, 21 in stageⅣgroup, and 5 in stageⅤgroup. There were significant differences in hemoglobin, eGFR, serum albumin, serum creatinine, serum urea nitrogen, and 24-hour urinary protein in DN patients with different CKD stages groups (P<0.05). Based on the TCM syndrome, there were 11 cases of Yin deficiency and dry heat syndrome, 23 of syndrome of deficiency of both Qi and Yin, 15 of liver-kidney Yin deficiency syndrome, and 29 of spleen-kidney Yang deficiency syndrome. Significant differences were found in hemoglobin, eGFR, serum total protein, serum albumin, serum creatinine, and serum urea nitrogen among DN patients with varying TCM syndrome types (P<0.05). There was a significant difference in the distribution of TCM syndrome types among DN patients in stageⅠ-Ⅴ CKD (P<0.05). In the stageⅠ group, the proportions of Yin deficiency and dry heat syndrome (5/11, 45.5%) and syndrome of deficiency of both Qi and Yin (3/11, 27.3%) were relatively high. In the stage Ⅱ group, the proportions of syndrome of deficiency of both Qi and Yin and liver-kidney Yin deficiency syndrome were 42.1% (8/19) and 31.6% (6/19) respectively. In the stageⅢ group, spleen-kidney Yang deficiency syndrome and syndrome of deficiency of both Qi and Yin accounted for 54.5% (12/22) and 31.8% (7/22), respectively. In the stageⅣ group, spleen-kidney Yang deficiency syndrome and liver-kidney Yin deficiency syndrome accounted for 52.4% (11/21) and 28.6% (6/21), respectively. In the stage Ⅴ group, spleen-kidney Yang deficiency syndrome occupied the highest proportion (3/5, 60.0%). Correspondence analysis indicated that Yin deficiency and dry heat syndrome, syndrome of deficiency of both Qi and Yin, and spleen-kidney Yang deficiency syndrome corresponded to CKD stageⅠ, Ⅱ andⅤ, respectively. Yang deficiency syndrome (OR=3.545, 95%CI=1.270-9.895, P=0.016) and heart location of disease (OR=3.208, 95%CI=1.082-9.511, P=0.035) were the influencing factors of DN combined with massive proteinuria. Yang deficiency syndrome (OR=3.000, 95%CI=1.141-7.890, P=0.026) was the influencing factor of DN combined with eGFR<60 mL·min-1· (1.73 m2) -1.
The distribution of TCM syndromes of DN transits from Yin deficiency and Qi deficiency to Yang deficiency with the worsening of CKD staging. Yang deficiency syndrome and disease location of heart are factors influencing DN with massive proteinuria, and Yang deficiency syndrome is influencing factor for DN with eGFR<60 mL·min-1· (1.73 m2) -1. TCM syndrome differentiation combined with modern medicine is conducive to grasping the pathogenesis of DN and advantaging integrated TCM and Western medicine diagnosis and treatment.
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.
To explore the association between blood pressure levels and the risk of CKD among the elderly in longevity areas of China.
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.
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) .
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.
Septic shock may lead to renal perfusion abnormalities, and even acute kidney injury (AKI) , seriously threatening the life of patients. Color Doppler ultrasound (CDU) can be used as a tool to evaluate changes of renal blood flow. However, there are few studies on its evaluation value for AKI in patients with septic shock.
To examine the value of CDU in assessing AKI and hemodynamic changes in patients with septic shock.
Participants were recruited from Xuzhou Central Hospital between June 2019 and July 2021, including 105 patients with septic shock, and 58 physical examinees. The general demographics and renal hemodynamic indices measured by CDU 〔the luminal diameter of renal artery (D) , peak systolic velocity (Vs) , end-diastolic velocity (Vd) , resistance index (RI) , pulsatility index (PI) 〕 were collected and compared with the groups. The renal hemodynamic indices were further compared between septic shock patients with and without AKI within 72 h after admission. The predictive value of renal hemodynamic indices for AKI in septic shock was analyzed by receiver operating characteristic (ROC) curve. The influencing factors of AKI in septic shock were explored by univariate and multivariate Logistic regression analyses. Then associations of the severity of AKI (stage 1, 2, 3 AKI) with renal hemodynamic indices were analyzed by Spearman rank analysis.
Thirty-nine septic shock patients had AKI within 72 h after admission, including 19 cases with stage 1 AKI, 15 with stage 2 AKI, and 5 with stage 3 AKI. Septic shock patients had lower D, Vs and Vd, and higher RI and PI than physical examinees (P<0.05) . Septic shock patients with AKI had lower D, Vs and Vd, and higher RI and PI than those without AKI (P<0.05) . AUC of D in predicting AKI in septic shock was 0.782 with 66.67% sensitivity and 80.30% specificity when 4.91 mm was chosen as the optimal cut-off value, that of Vs was 0.772 with 94.87% sensitivity and 51.52% specificity when 71.19 cm/s was chosen as the optimal cut-off value, that of Vd was 0.708 with 58.97% sensitivity and 77.27% specificity when 17.19 cm/s was chosen as the optimal cut-off value, that of RI was 0.842 with 87.18% sensitivity and 66.67% specificity when 0.71 was chosen as the optimal cut-off value, and that of PI was 0.683 with 56.41% sensitivity and 78.79% specificity when 1.50 was chosen as the optimal cut-off value. Multivariate Logistic regression analysis showed that D≥4.91 mm, Vs≥71.19 cm/s and RI≥0.71 were associated with AKI in septic shock (P<0.05) . Patients with stage 3 AKI had lower D, and higher RI than those with stage 2 AKI (P<0.05) . Patients with stage 3 AKI had lower D, Vs and Vd, and higher RI than those with stage 1 AKI (P<0.05) . Patients with stage 2 AKI had lower Vd than those with stage I AKI (P<0.05) . Spearman rank analysis showed that both the D and Vd were strongly negatively correlated with the severity of AKI, and Vs was weakly negatively correlated with it (rs=-0.421, -0.674, -0.358, P<0.05) . RI was strongly positively correlated with the severity of AKI (rs=0.539, P<0.001) . PI was not significantly correlated with the severity of AKI (P>0.05) .
CDU could detect the changes of renal hemodynamics in patients with septic shock. Renal hemodynamic indices are related to the development and severity of AKI, which could be used as diagnostic markers or predictors of AKI in septic shock. So it may be possible to diagnose and predict AKI in septic shock by detecting renal hemodynamic indices.
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) .
To understand the effect of probiotics, a microbiota-modulating agent, administered based on gut flora status in patients with DN.
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.
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.
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.
Hyperuricemia (HUA) caused by elevated serum uric acid (SUA) has been shown to be an independent risk factor for the development and progression of chronic kidney disease (CKD). However, there are few cohort studies on the correlation of SUA level with the development and progression of CKD in the elderly of China.
To explore the association of baseline SUA level and its changes with the risk of chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) in the elderly in longevity areas of China.
Based on the Healthy Aging and Biomarkers Cohort Study (HABCS), a sub cohort of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), the older adults who received physical examination and with biomedical indicators in 2012 and 2014 were selected as the study subjects from December 2021 to May 2022. The age, gender, blood pressure, blood lipids, blood glucose and other biomedical indicators were collected at baseline and follow-up period. Cox proportional hazards regression model was used to analyze the association of different SUA levels with the risk of CKD. Spearman rank correlation and generalized linear model analysis were used to analyze the association between baseline SUA level and baseline eGFR level and the linear correlation between changes in SUA level and eGFR changes in the elderly, respectively.
A total of 981 subjects were included in the study, with the median age of 79 (70, 88) years, the prevalence of HUA of 6.8% (67/981), the cumulative follow-up of 2 029 person-years and the median follow-up of 2.05 years, including 179 new cases of CKD, the cumulative incidence of CKD during the follow-up was 18.2%〔95%CI (15.9%, 20.8%) 〕, and the incidence density was 88.22/1 000 person-years〔95%CI (76.24/1 000 person-years, 101.41/1 000 person-years) 〕. Cox proportional hazards regression analysis with SUA quartile grouping as the independent variable showed that compared with the lowest quartile group of baseline SUA level (Q1), the HR value for the risk of CKD in the highest quartile group of baseline SUA level (Q4) was 2.08〔95%CI (1.27, 3.41), P=0.004〕. Cox proportional hazards regression analysis with SUA level as the independent variable showed that, for every 10 μmol/L increase in baseline SUA level, the risk of CKD in the elderly increased by 4% (P<0.001). Cox proportional hazards regression analysis with HUA as the independent variable showed an increased risk of CKD in elderly with HUA compared to those without HUA, with the HR value of 2.00〔95%CI (1.20, 3.24), P=0.007〕. The median baseline SUA was 270.60 (223.10, 325.90) μmol/L, the median baseline eGFR was 84.07 (73.08, 98.38) mL·min-1· (1.73 m2) -1 in the elderly. Spearman rank correlation analysis showed a negative correlation between the above two (rs=-0.363, P<0.001). The results of generalized linear model analysis showed that for every 10 μmol/L increase in baseline SUA level, the baseline eGFR decreased by 0.897 mL·min-1· (1.73 m2) -1 (P<0.001). The median change of SUA level was -3.55 (-40.60, 31.90) μmol/L and the median change of eGFR was 3.49 (-8.13, 15.89) mL·min-1· (1.73 m2) -1 in the elderly during the follow-up period of this study, and Spearman rank correlation analysis showed a negative correlation between the above two (rs=-0.355, P<0.001). The results of the generalized linear model analysis showed that for every 10 μmol/L increase in SUA level in the elderly during the follow-up period, eGFR decreased by 1.027 mL·min-1· (1.73 m2) -1 in the elderly (P<0.001) .
Elevated SUA level in the elderly is associated with an increased risk of CKD and a declined eGFR in China.
Understanding the condition and influencing factors of cognitive impairment in maintenance hemodialysis (MHD) patients could signficantly enhance their quality of life while alleviating the burden on their families and society.
TO investigate the status of cognitive impairment in MHD patients and explore the possible influencing factors.
Using convenience sampling, we selected MHD patients from three hemodialysis centers (including the Department of Nephrology at the First Affiliated Hospital of Shihezi University, the Department of Nephrology at Shihezi People's Hospital, and the Langshen Hemodialysis Center) in Shihezi City between April 2023 and April 2024. We collected data on demographic characteristics, cognitive impairment levels, sleep quality, independent living abilities, serum levels of α-Klotho, β-Klotho, FGF-23, and other common laboratory indicators. Cognitive function was assessed with the Montreal Cognitive Assessment (MoCA), sleep quality was evaluated with the Athens Insomnia Scale (AIS-8), and independent living ability was assessed using the Functional Activities Questionnaire (FAQ). Serum levels of α-Klotho, β-Klotho, and FGF-23 were measured by the ELISA method. Univariate and multivariate Logistic regression analyses were performed to identify influencing factors, which were validated for their predictive value on cognitive impairment using the receiver operating characteristic (ROC) curve. A nomogram was subsequently plotted.
A total of 276 MHD patients were surveyed, revealing a cognitive impairment incidence rate of 76.4% (211/276). Among these, 145 patients had mild cognitive impairment and 66 patients had moderate cognitive impairment. Nearly half of the patients exhibited suspected insomnia (21.4%) or confirmed insomnia (25.4%). Among the patients studied, 14.9% (41 out of 276) lacked the ability to live independently. The multivariate Logistic regression analysis indicated that age (OR=1.038, 95%CI=1.004-1.072) and sleep disorders (OR=1.179, 95%CI=1.051-1.322) were risk factors for cognitive impairment in MHD patients (P<0.05). High serum α-Klotho levels (OR=0.996, 95%CI=0.994-0.998), high serum β-Klotho levels (OR=0.750, 95%CI=0.661-0.852), and higher years of education (OR=0.800, 95%CI=0.699-0.915) were protective factors (P<0.05). The area under the ROC curve (AUC) showed that age (AUC=0.732, 95%CI=0.667-0.797), sleep disorder (AUC=0.710, 95%CI=0.638-0.783), α-Klotho (AUC=0.774, 95%CI=0.709-0.839), β-Klotho (AUC=0.741, 95%CI=0.663-0.819) and years of education (AUC=0.718, 95%CI=0.647-0.789) had predictive value for cognitive impairment in MHD patients. The combination of age, sleep disorder, serum α-Klotho, serum β-Klotho and years of education (P=-0.004×α-Klotho-0.287×β-Klotho+0.370×age-0.223×years of education +0.165×AIS-8 score+6.658) predicted the occurrence of MHD. The AUC of cognitive impairment was 0.894 (95%CI=0.851-0.937, P<0.001), the sensitivity was 82.9%, and the specificity was 78.5%.
The prevalence of cognitive impairment among MHD patients is substantially high, estimated at approximately 76%. Age, sleep disorders, years of education, and levels of α-Klotho and β-Klotho are important influencing factors. Medical staff and patients' families should raise awareness of cognitive impairment, actively screen and intervene in key patients to improve their quality of life and reduce the burden on their families and society.
Diabetes nephropathy (DN) is a common complication of diabetes patients. The prediction and validation of its risk will help identify high-risk patients in advance and take intervention measures to avoid or delay the progress of nephropathy.
To analyze the risk factors affecting the complication of DN in patients with type 2 diabetes mellitus (T2DM) , construct a risk prediction model for the risk of DN in T2DM patients and validate it.
A total of 5 810 patients with T2DM admitted to the First Affiliated Hospital of Xinjiang Medical University from January 2016 to June 2021 were selected as the study subjects and divided into the DN group (n=481) and non-DN group (n=5 329) according to the complication of DN. A 1∶1 case-control matching was performed on 481 of these DN patients and non-DN patients by gender and age (±2 years) , and the matched 962 T2DM patients were randomly divided into the training group (n=641) and validation group (n=321) based on a 2∶1 ratio. Basic data of patients, such as clinical characteristics, laboratory test results and other related data, were collected. LASSO regression was applied to optimize the screening variables, and a nomogram prediction model was developed using multivariate Logistic regression analysis. The discriminability, calibration and clinical validity of the prediction model were evaluated by using the receiver operating characteristic (ROC) curve, Hosmer-Lemeshow calibration curve, and decision curve analysis (DCA) , respectively.
There were significant differences in gender, age, BMI, course of diabetes, white blood cell count, total cholesterol, triacylglycerol, low-density lipoprotein cholesterol, serum creatinine, hypertension, systolic blood pressure, diastolic blood pressure, glycosylated hemoglobin, apolipoprotein B, 24-hour urinary micro total protein, qualitative urinary protein between the DN and non-DN group (P<0.05) . Five predictor variables associated with the risk of DN in patients with T2DM were screened using LASSO regression analysis, and the results combined with multivariate Logistic regression analysis showed that duration of diabetes, total cholesterol, serum creatinine, hypertension, and qualitative urinary protein were risk factors for the complication of DN in T2DM patients (P<0.05) . The area under the ROC curve (AUC) for the risk of DN in the training group of the model was 0.866 (95%CI=0.839-0.894) , and the AUC for predicting the risk of DN in the validation group was 0.849 (95%CI=0.804-0.889) based on the predictor variables. The Hosmer-Lemeshow calibration curve fit was good (P=0.748 for the training group; P=0.986 for the validation group) . DCA showed that the use of nomogram prediction model was more beneficial in predicting DN when the threshold probability of patients was 0.15 to 0.95.
The nomogram prediction model containing five predictor variables (diabetes duration, total cholesterol, serum creatinine, hypertension, qualitative urinary protein) developed in this study can be used to predict the risk of DN in patients with T2DM.
Diabetic nephropathy is one of the most common complications of diabetic microangiopathy, which significantly reduces the quality of life of diabetic patients and is the main cause of end-stage renal failure. As one of the main drugs in the treatment of diabetes mellitus, metformin plays a vital role in the treatment of diabetic nephropathy. In recent years, studies have found that metformin can not only lower blood sugar through a variety of mechanisms, but also prevent diabetic kidney disease from developing into end-stage renal failure. Several studies have found that metformin has clinical efficacy in the treatment of diabetic nephropathy, and drug safety in patients should be evaluated by glomerular filtration rate. This review summarizes the results of the clinical effects and mechanism of metformin in the treatment of diabetic nephropathy, aiming to better understand the therapeutic effect of metformin on diabetic nephropathy, and provide reference for the treatment of diabetic nephropathy.
Nephrotic syndrome (NS) is a common chronic kidney disease in children, and has a long treatment cycle with being prone to recurrence and refractoriness. Adverse effects caused by therapeutic drugs and concerns about disease prognosis may all affect the child's physical and mental health, and quality of life. Therefore, it is very necessary to understand the Health-related Quality of Life (HRQOL) of children with nephrotic syndrome.
To understand the level of HRQOL in children with nephrotic syndrome.
Children (aged 2-18 years) with nephrotic syndrome and their parents were recruited from the Department of Pediatric Nephrology Rheumatism and Immunology, Shengjing Hospital of China Medical University between October 2019 and December 2020. Data were collected on age, gender, disease duration, whether they had frequent relapses, number of relapses, and whether they were prescribed immunosuppressive agents (including cyclophosphamide, tacrolimus, etc.) , place of residence (urban, rural, urban-rural junction areas) . The PedsQL 4.0 core generic scale was used to understand the level of HRQOL (including the child self rating scale and parent report) in children with primary NS.
A total of 183 questionnaires were distributed, and 174 valid questionnaires were returned, with an effective recovery rate of 95.1%. Among the 174 children, 119 were males and 55 were females. Median age was 6 (4, 11) years. There were 100 children with recurrence (57.5%) , with a median number of 3 (1, 5) recurrences. 54 patients had frequent recurrences and 46 patients had non frequent recurrences. 31 patients were treated with immunosuppressants. The usual place of residence was urban in 86 patients, rural in 63 patients, and urban-rural junctions in 25 patients. The ICC of the concordance analysis between the children's self-rating scale and the parent-reported scale were both greater than 0.75. There were no significant differences in physiological scores, emotional scores, social scores, role scores and total scores between genders (P>0.05) . There were statistically significant differences in physiological scores, emotional scores, social scores and total scores among different ages (P<0.05) . However, there was no significant difference in the role scores at different ages (P>0.05) . There were no significant differences in the physiological scores, emotional scores, social scores, role scores, and total scores among different disease durations (P>0.05) . There were no significant differences in the physiological score, emotional score, social score, role score and total score between children with and without frequent recurrence (P>0.05) . The emotional scores, social scores, and total scores were significantly different between children who used immunosuppressants and those who did not use (P<0.05) , and those who did not apply immunosuppressants achieved a higher score. There were no significant differences in the physiological scores, emotional scores, social scores, role scores and total scores among different family residing places (P>0.05) .
The scores of children with NS in physical, emotional, social, and role functioning were reduced. When treating the disease, clinicians need to focus on the children's physical, psychological and social adaptability, and intervene in time to improve their quality of life.
Klotho is closely related to the occurrence and development of kidney disease. Salt-sensitive hypertension (SSH) is often accompanied by kidney disease. At present, there are few reports on the role and molecules mechanism of klotho in renal injury in SSH.
To investigate the role and molecules mechanism of klotho in renal injury in SSH.
The rat glomerular mesangial cell line HBZY1 was selected as the experimental cells from June 2021 to January 2022, and the experimental cells were divided into the control group and the model group. The model of HBZY1 cell injury induced by NaCl 137 mmol/L and angiotensin Ⅱ (Ang Ⅱ) 10-6 mmol/L was used to simulate the renal injury in SSH, and the cells were collected. The differences in the expression of klotho mRNA and protein were detected by real-time fluorescent quantitative PCR (qRT-PCR) and Western Blot. The interference vector and overexpression vector of klotho and the overexpression vector of angiotensin Ⅱ type 1 receptor (AT1R) were constructed. The klotho interference experiments were divided into five groups, including the control group, empty group, klotho-siRNA1 group, klotho-siRNA2 group and klotho-siRNA3 group; the klotho overexpression experiments were divided into three groups, including the control group, empty group and klotho overexpression group; the AT1R overexpression experiments were divided into three groups, including the control group, empty group and AT1R overexpression group. The constructed vectors were transfected into cells with verified transfection efficiency. After successful transfection, the experiment was divided into two parts. The first part of the experiment was to verify the renal protective effect of klotho, the experiment subjects were divided into four groups, including the control group, model group, klotho overexpression group and klotho interference group. The second part of the experiment was to explore whether the renal protective effect of klotho was related to AT1R, the experiment subjects were divided into three groups, including the model group, klotho overexpression group and klotho+AT1R overexpression group. After successful transfection, the tests including cell viability detected by cell counting kit-8 (CCK-8) method, reactive oxygen species (ROS) content detected by flow cytometry, malondialdehyde (MDA) and superoxide dismutase (SOD) content in cell supernatant detected by enzyme-linked immunosorbent assay (ELISA) , interaction effect between kltho and AT1R detected by co-immunoprecipitation (Co-IP) .
Compared with the control group, mRNA level and protein expression of klotho in the model group decreased in model group (t=7.102, 7.506; P=0.002, 0.002) , klotho-siRNA2 interference effect was more significant (P<0.001) , the expression of klotho protein in the klotho overexpression group increased significantly (P<0.001) , the expression of AT1R protein in the overexpression group increased significantly (P<0.001) . Effects of klotho on cell viability and oxidative stress injury: compared with the control group, cell viability in the model group decreased (P<0.001) , intracellular ROS and MDA content increased (P<0.001, P=0.004) , and SOD content decreased (P=0.041) ; compared with the model group, cell viability in the klotho overexpression group increased (P<0.001) , intracellular ROS and MDA content decreased and SOD content increased (P<0.001, P=0.003, P=0.018) ; compared with the model group, cell viability in the klotho interference group decreased (P<0.001) , while intracellular ROS and MDA content increased and SOD content decreased (P<0.001, P=0.002, P=0.001) . Effects of klotho on cell viability and oxidative stress injury through AT1R: compared with the model group, cell viability increased (P<0.001) , intracellular ROS and MDA content decreased and SOD content increased (P<0.001, P=0.024, P=0.007) in the klotho overexpression group; compared with the klotho overexpression group, cell viability decreased (P<0.001) , ROS and MDA content increased and SOD content decreased (P<0.001, P=0.001, P=0.002) in the klotho+AT1R overexpression group. Co-IP determined that there was an interaction between klotho and AT1R.
Klotho plays a protective role in renal injury in SSH by inhibiting oxidative stress injury through interaction with AT1R.
The quality of life of patients with nephrotic syndrome requires a lot of focus, and improvements. A relevant scale can be used to measure it, but there is no nephrotic syndrome-specific quality of scale.
To develop a Quality of Life Instruments for Chronic Diseases-Nephrotic Syndrome〔QLICD-NS (V2.0) 〕 combined with QLICD-GM (V2.0), then verify it using the classical test theory.
From 2017 to 2021, an item pool was established according to literature review and the results of a semi-structured questionnaire, then the items were screened in accordance with a pre-test and importance score rated by physicians and patients, after that, the draft of the QLICD-NS (V2.0) was developed. The draft version was tested using onsite interview and questionnaire survey in nephrotic syndrome patients treated in Department of Nephrology, the Affiliated Hospital of Guangdong Medical University from March to November 2021. The first measurement was conducted on the day of admission, the second measurement was conducted with some of the patients, and the third measurement was conducted on the day of discharge. The coefficient of variation, correlation coefficient and Cronbach's α, factor analysis and classical test theory were used to evaluate QLICD-NS (V2.0) .
The QLICD-NS (V2.0) contains 15 items, belonging to three domains of clinical symptoms, adverse drug reactions and psychological effects. The Cronbach's α measuring the split-half reliability was greater than 0.7 for the scale and each of the three domains. With the Chinese version of SF-36 as the calibration standard, the domains of the QLICD-NS (V2.0) were highly correlated with their counterpart domains of the Chinese version of SF-36. The standardized response mean was greater than 0.80 for all domains and items (except for the cognition and social support items), indicating that the responsiveness of the QLICD-NS (V2.0) was good. Scanning the QR code in the text can obtain the detailed evaluation of the scale.
The QLICD-NS (V2.0) compiled by us includes 15 items, and has proven with good reliability, validity and responsiveness.