Association of urinary acidification function with the progression of diabetic kidney disease in patients with type 2 diabetes
Association of urinary acidification function with the progression of diabetic kidney disease in patients with type 2 diabetes
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2型糖尿病患者尿酸化功能与糖尿病肾病进展的关系
DOI：
10.1016/j.jdiacomp.2019.107419
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发表时间：
2019
影响因子：
3
通讯作者：
Changying Xing
中科院分区：
文献类型：
--
作者：
Huanhuan Zhu;Xi Liu;Chengning Zhang;Li Qing;Xiaofei An;Simeng Liu;Lin Wu;Bo Zhang;Yanggang Yuan;Changying Xing
摘要目的虽然糖尿病肾病（DKD）在过去几十年中一直被认为是一种肾小球中心性疾病，但越来越多的证据表明肾小管损害在其发病和进展中是不可或缺的。本研究旨在探讨2型糖尿病患者尿酸化功能障碍与DKD进展的关系。方法对80例经肾活检证实的DKD患者进行了尿酸化功能测定。分析肾小管转运功能障碍的类型，包括碳酸氢盐重吸收功能障碍、可滴定酸分泌功能障碍和铵分泌功能障碍。此外，患者随访17个月（四分位距，11-32），以评估尿酸化功能障碍在DKD进展中的作用。结果尿酸化功能障碍以氨分泌障碍最常见，占53.75%。尿可滴定酸紊乱组尿蛋白排泄量明显高于正常组，肾小球滤过率（GFR）明显低于正常组，尿铵分泌紊乱组亦明显低于正常组。尿可滴定酸与eGFR呈正相关，而与蛋白尿、血清肌酐和BUN呈负相关。此外，24 h尿蛋白、血清肌酐、BUN和胱抑素C从DKD II期到IV期增加，而eGFR和尿可滴定酸以相同的方式降低。Kaplan-Meier分析和考克斯回归分析显示可滴定酸紊乱是DKD进展的独立危险因素。结论尿可滴定酸异常是DKD患者蛋白尿、eGFR及肾小球病变程度的潜在生物标志物。此外，可滴定酸障碍是DKD进展的独立危险因素。
Abstract Objective Although diabetic kidney disease (DKD) has been considered as a glomerulocentric disease in the past few decades, growing evidence demonstrated that tubular damage was indispensable in its pathogenesis and progression. This study was designed to investigate the association of urinary acidification dysfunction with the progression of DKD in type 2 diabetic patients. Methods Here the urinary acidification functions were measured from 80 participants with renal biopsy-proven DKD. The different kinds of renal tubular transportation dysfunction were analyzed, including the dysfunction of bicarbonate reabsorption, titratable acid secretion, and ammonium secretion. In addition, patients were followed up for 17 (interquartile range, 11–32) months to evaluate the effect of urinary acidification dysfunction in the progression of DKD. Results The most common urinary acidification dysfunction was the disorder of ammonium secretion, accounting for 53.75%. The more proteinuria excretion and the lower glomerular filtration rate (GFR) were observed in the urinary titratable acid disorder group than the normal group, and the same results were obtained for ammonium secretion disorder. Urine titratable acid was positively correlated with eGFR whereas it was inversely correlated with proteinuria, serum creatinine, and BUN. Moreover, 24 h urine protein, serum creatinine, BUN and cystatin C increased from DKD stage II to stage IV, whereas the eGFR and urine titratable acid decreased in the same way. Furthermore, Kaplan-Meier analysis and Cox regression showed that the disorder of titratable acid was an independent risk factor for DKD progression. Conclusions The dysfunction of urinary titratable acid is a potential biomarker for the severity of proteinuria, eGFR and glomerular lesions in patients with DKD. Moreover, the titratable acid disorder is an independent risk factor of the DKD progression.