Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.
Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
J Diabetes Complications. 2019 Nov;33(11):107419. doi: 10.1016/j.jdiacomp.2019.107419. Epub 2019 Aug 19.
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.
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.
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.
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.
尽管在过去几十年中，糖尿病肾病（DKD）被认为是一种以肾小球为中心的疾病，但越来越多的证据表明，肾小管损伤在其发病机制和进展中不可或缺。本研究旨在探讨尿酸化功能障碍与 2 型糖尿病患者 DKD 进展的关系。
本研究测量了 80 名经肾活检证实为 DKD 的患者的尿酸化功能。分析了各种肾小管转运功能障碍，包括碳酸氢盐重吸收、滴定酸分泌和铵分泌功能障碍。此外，对患者进行了 17 个月（中位数，11-32 个月）的随访，以评估尿酸化功能障碍对 DKD 进展的影响。
最常见的尿酸化功能障碍是铵分泌障碍，占 53.75%。与正常组相比，尿滴定酸障碍组的蛋白尿排泄量更高，肾小球滤过率（GFR）更低，铵分泌障碍组也有同样的结果。尿滴定酸与 eGFR 呈正相关，与蛋白尿、血清肌酐和 BUN 呈负相关。此外，24 小时尿蛋白、血清肌酐、BUN 和胱抑素 C 从 DKD Ⅱ期增加到Ⅳ期，而 eGFR 和尿滴定酸则呈下降趋势。进一步的 Kaplan-Meier 分析和 Cox 回归表明，滴定酸障碍是 DKD 进展的独立危险因素。
尿滴定酸功能障碍是 DKD 患者蛋白尿严重程度、eGFR 和肾小球病变的潜在生物标志物。此外，滴定酸障碍是 DKD 进展的独立危险因素。
