Clinicopathological Features of Anticancer Drug-induced Kidney Injury

doi:10.12114/j.issn.1007-9572.2022.0372

Chinese General Practice ›› 2022, Vol. 25 ›› Issue (33): 4153-4158.DOI: 10.12114/j.issn.1007-9572.2022.0372

Special Issue: 肿瘤最新文章合辑；泌尿系统疾病最新文章合辑

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Clinicopathological Features of Anticancer Drug-induced Kidney Injury

Hebei Clinical Research Center for Chronic Kidney Disease/Hebei Key Laboratory of Vascular Calcification in Kidney Disease/Department of Nephrology, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China

Received:2022-03-19 Revised:2022-08-06 Published:2022-11-20 Online:2022-09-01
Contact: XU Jinsheng
About author:
GENG T H, LI H, JIN J J, et al. Clinicopathological features of anticancer drug-induced kidney injury[J]. Chinese General Practice, 2022, 25 (33) : 4153-4158, 4167.

抗肿瘤药物相关肾损害患者的临床病理特点分析

050011　河北省石家庄市，河北省慢性肾病临床医学研究中心　河北省肾脏病血管钙化重点实验室　河北医科大学第四医院肾内科

通讯作者: 徐金升
作者简介:
耿同会，李涵，靳晶晶，等.抗肿瘤药物相关肾损害患者的临床病理特点分析[J].中国全科医学，2022，25（33）：4153-4158，4167. [www.chinagp.net] 作者贡献：白亚玲、徐金升提出研究思路，设计研究方案，研究命题的提出、设计；耿同会、李涵负责数据收集、整理和统计学分析，图表的绘制，结果的可视化呈现，负责论文起草、初步撰写；靳晶晶、程美娟、张胜雷负责论文审阅、修改；徐金升负责最终版本修订，对论文负责。
基金资助:
河北省医学技术跟踪项目(G2018050); 河北省重点研发计划项目(20377704D); 河北省科技计划项目(16397733D)

Abstract

Abstract:

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.

Key words: Neoplasms, Antineoplastic agents, Renal damage, Clinical features, Pathological features, Disease attributes

摘要：

背景

肿瘤治疗措施导致的肾损害日益多见，而该领域关于相应患者肾脏病理的研究较少。

目的

分析抗肿瘤药物相关肾损害患者的临床及肾脏病理特点。

方法

选取2013年10月至2021年8月在河北医科大学第四医院肾内科住院并行肾穿刺活检的≥18岁患者112例，肾损害出现时间位于发现肿瘤后或者与肿瘤同一时间出现，肾损害与恶性肿瘤或者肿瘤相关治疗存在直接或间接关系；既往应用化疗、分子靶向药物或免疫检查点抑制剂等全身治疗的患者纳入抗肿瘤药物组（65例），其余患者纳入未用抗肿瘤药物组（47例）。收集患者的一般资料、实验室检查和病理资料。分析抗肿瘤药物相关肾损害患者的临床及肾脏病理特点。

结果

抗肿瘤药物组中59例实体瘤患者发生急性肾损伤（AKI）30例（50.8%），6例血液系统肿瘤患者发生AKI 4例（4/6）。未用抗肿瘤药物组35例实体瘤患者中发生AKI 11例（31.4%），12例血液系统肿瘤患者发生AKI 6例（50.0%）。抗肿瘤药物组治疗前血肌酐低于治疗后（P<0.001）。抗肿瘤药物组性别、吸烟比例、血清白蛋白、尿蛋白阳性率与未用抗肿瘤药物组比较，差异有统计学意义（P<0.05）；两组年龄、血红蛋白、血肌酐、尿素氮、尿酸、D-二聚体、糖尿病比例、高血压比例、总胆固醇、三酰甘油、尿蛋白定量、AKI发生率比较，差异无统计学意义（P>0.05）。抗肿瘤药物组实体瘤患者肾脏病理表现为肾小管间质损伤的比例高于未用抗肿瘤药物组（P=0.023），而膜性肾病的比例较未用抗肿瘤药物组低（P=0.004）。抗肿瘤药物组最主要的病理表现为肾小管间质损伤34例（52.3%），未用抗肿瘤药物组最主要的病理表现为膜性肾病18例（38.3%）、肾小管间质损伤18例（38.3%）。

结论

抗肿瘤药物相关肾损害患者的临床及病理存在多种类型，抗肿瘤药物可能会导致肾功能的损害，应用期间应警惕肾小管间质损伤。

关键词: 肿瘤, 抗肿瘤药, 肾损害, 临床特点, 病理特点, 疾病特征

GENG Tonghui,LI Han,JIN Jingjing, et al. Clinicopathological Features of Anticancer Drug-induced Kidney Injury[J]. Chinese General Practice, 2022, 25(33): 4153-4158. DOI: 10.12114/j.issn.1007-9572.2022.0372.
耿同会,李涵,靳晶晶等. 抗肿瘤药物相关肾损害患者的临床病理特点分析[J]. 中国全科医学, 2022, 25(33): 4153-4158. DOI: 10.12114/j.issn.1007-9572.2022.0372.

Figures/Tables 5

References 30

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组别	例数	性别（男/女）	年龄（±s，岁）	吸烟〔n（%）〕	血红蛋白（g/L）	血清白蛋白（±s，g/L）	血肌酐〔M（QR），μmol/L〕	尿素氮〔M（QR），mg/dl〕	尿酸〔M（QR），μmol/L〕
抗肿瘤药物组	65	38/27	58.9±10.2	20（30.8）	106.0（29.3）	32.9±7.8	128.7（161.1）	8.1（8.0）	390.3（169.2）
未用抗肿瘤药物组	47	10/37	59.3±11.8	29（61.7）	109.4±27.1	29.6±9.5	105.0（187.6）	8.8（8.9）	395.4（158.5）
检验统计量值		5.062^a	0.249^b	10.606^a	-0.233^c	-2.120^b	-0.315^c	-0.399^c	-1.275^c
P值		0.024	0.862	0.001	0.816	0.034	0.752	0.690	0.202
组别	D-二聚体〔M（QR），ng〕	糖尿病〔n（%）〕	高血压〔n（%）〕	总胆固醇〔M（QR），mmol/L〕	三酰甘油〔M（QR），mmol/L〕	尿蛋白阳性〔n（%）〕	尿蛋白定量〔M（QR），mg/24 h〕	急性肾损伤〔n（%）〕
抗肿瘤药物组	0.54（1.32）	9（13.8）	35（53.8）	1.75（1.49）	4.81（2.08）	43（66.2）	2 616（3 879）	34（52.3）
未用抗肿瘤药物组	0.81（1.36）	6（12.8）	25（53.2）	1.68（1.11）	5.40（3.72）	42（89.4）	4 117（6 755）	17（36.2）
检验统计量值	-0.960^c	0.027^a	0.005^a	-0.131^c	-0.497^c	8.030^a	-1.599^c	2.864^a
P值	0.337	0.868	0.945	0.896	0.619	0.005	0.066	0.091

组别	例数	性别（男/女）	年龄（±s，岁）	吸烟〔n（%）〕	血红蛋白（g/L）	血清白蛋白（±s，g/L）	血肌酐〔M（QR），μmol/L〕	尿素氮〔M（QR），mg/dl〕	尿酸〔M（QR），μmol/L〕
抗肿瘤药物组	65	38/27	58.9±10.2	20（30.8）	106.0（29.3）	32.9±7.8	128.7（161.1）	8.1（8.0）	390.3（169.2）
未用抗肿瘤药物组	47	10/37	59.3±11.8	29（61.7）	109.4±27.1	29.6±9.5	105.0（187.6）	8.8（8.9）	395.4（158.5）
检验统计量值		5.062^a	0.249^b	10.606^a	-0.233^c	-2.120^b	-0.315^c	-0.399^c	-1.275^c
P值		0.024	0.862	0.001	0.816	0.034	0.752	0.690	0.202
组别	D-二聚体〔M（QR），ng〕	糖尿病〔n（%）〕	高血压〔n（%）〕	总胆固醇〔M（QR），mmol/L〕	三酰甘油〔M（QR），mmol/L〕	尿蛋白阳性〔n（%）〕	尿蛋白定量〔M（QR），mg/24 h〕	急性肾损伤〔n（%）〕
抗肿瘤药物组	0.54（1.32）	9（13.8）	35（53.8）	1.75（1.49）	4.81（2.08）	43（66.2）	2 616（3 879）	34（52.3）
未用抗肿瘤药物组	0.81（1.36）	6（12.8）	25（53.2）	1.68（1.11）	5.40（3.72）	42（89.4）	4 117（6 755）	17（36.2）
检验统计量值	-0.960^c	0.027^a	0.005^a	-0.131^c	-0.497^c	8.030^a	-1.599^c	2.864^a
P值	0.337	0.868	0.945	0.896	0.619	0.005	0.066	0.091

抗肿瘤药物组	例数	未用抗肿瘤药物组	例数
肾小管间质损伤	19	膜性肾病	16
膜性肾病	11	肾小管间质损伤	8
IgA肾病	7	IgA肾病	5
局灶节段性肾小球硬化症伴肾小管间质损伤	5	管型肾病伴肾小管间质损伤	3
管型肾病伴肾小管间质损伤	3	缺血性肾损伤	3
缺血性肾病伴肾小管间质损伤	2	膜性肾病伴肾小管间质损伤	2
IgA肾病伴缺血性肾损伤	2	IgA肾病伴肾小管间质损伤	2
缺血性肾损伤	2	局灶节段性肾小球硬化症	1
IgA肾病伴肾小管间质损伤	2	抗中性粒细胞胞浆抗体相关小血管炎肾损害	1
系膜增生性肾小球病	2	系膜增生性肾小球病	1
肾淀粉样变性伴管型肾病	2	肾淀粉样变性伴肾小管间质损伤	1
系膜增生性肾小球病伴肾小管间质损伤	1	肾淀粉样变性	1
毛细血管内皮细胞病	1	管型肾病	1
血栓性微血管病	1	系膜增生性肾小球病伴肾小管间质损伤	1
肾小球微小病变	1	局灶节段性肾小球硬化症伴肾小管间质损伤	1
肾淀粉样变性	1
局灶节段性肾小球硬化症	1
膜性肾病伴肾小管间质损伤	1
足细胞病伴肾小管间质损伤	1

抗肿瘤药物组	例数	未用抗肿瘤药物组	例数
肾小管间质损伤	19	膜性肾病	16
膜性肾病	11	肾小管间质损伤	8
IgA肾病	7	IgA肾病	5
局灶节段性肾小球硬化症伴肾小管间质损伤	5	管型肾病伴肾小管间质损伤	3
管型肾病伴肾小管间质损伤	3	缺血性肾损伤	3
缺血性肾病伴肾小管间质损伤	2	膜性肾病伴肾小管间质损伤	2
IgA肾病伴缺血性肾损伤	2	IgA肾病伴肾小管间质损伤	2
缺血性肾损伤	2	局灶节段性肾小球硬化症	1
IgA肾病伴肾小管间质损伤	2	抗中性粒细胞胞浆抗体相关小血管炎肾损害	1
系膜增生性肾小球病	2	系膜增生性肾小球病	1
肾淀粉样变性伴管型肾病	2	肾淀粉样变性伴肾小管间质损伤	1
系膜增生性肾小球病伴肾小管间质损伤	1	肾淀粉样变性	1
毛细血管内皮细胞病	1	管型肾病	1
血栓性微血管病	1	系膜增生性肾小球病伴肾小管间质损伤	1
肾小球微小病变	1	局灶节段性肾小球硬化症伴肾小管间质损伤	1
肾淀粉样变性	1
局灶节段性肾小球硬化症	1
膜性肾病伴肾小管间质损伤	1
足细胞病伴肾小管间质损伤	1

化疗	例数	分子靶向药物	例数	免疫治疗	例数
肾小管间质损伤	13	肾小管间质损伤	5	肾小管间质损伤	3
膜性肾病	10	缺血性肾损伤伴肾小管间质损伤	2	IgA肾病	3
局灶节段性肾小球硬化症伴肾小管间质损伤	5	肾小球微小病变	1	膜性肾病伴肾小管间质损伤	1
IgA肾病	3	系膜增生性肾小球病	1	系膜增生性肾小球病伴肾小管间质损伤	1
缺血性肾损伤	2	IgA肾病	1
管型肾病伴肾小管间质损伤	2	IgA肾病伴缺血性肾损伤	1
IgA肾病伴肾小管间质损伤	1	IgA肾病伴肾小管间质损伤	1
系膜增生性肾小球病	1	局灶节段性肾小球硬化症	1
血栓性微血管病	1	足细胞病伴肾小管间质损伤	1
管型肾病	1
IgA肾病伴缺血性肾损伤	1
肾淀粉样变伴管型肾病	1
肾淀粉样变	1
毛细血管内皮细胞病	1

Clinicopathological Features of Anticancer Drug-induced Kidney Injury

抗肿瘤药物相关肾损害患者的临床病理特点分析

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组别	例数	膜性肾病	肾小管间质损伤	IgA肾病
抗肿瘤药物组	59	12（20.3）	31（52.5）	11（18.6）
未用抗肿瘤药物组	35	17（48.6）	10（28.6）	6（17.1）
χ²值		8.509	5.133	0.033
P值		0.004	0.023	0.855

变量	β	SE	Wald χ²值	P值	OR（95%CI）
吸烟	0.658	0.414	2.528	0.112	1.930（0.858，4.343）
性别	-0.791	0.423	3.507	0.061	0.453（0.198，1.038）
年龄	0.264	0.336	0.619	0.432	1.302（0.674，2.514）
肿瘤类型	1.451	0.493	8.655	0.003	4.267（1.623，11.220）
治疗措施1	0.244	0.408	0.358	0.550	1.277（0.574，2.841）
治疗措施2	0.835	0.481	3.013	0.083	2.305（0.898，5.918）
治疗措施3	2.266	0.569	15.868	<0.001	9.644（3.162，29.413）

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