A more tubulocentric view of diabetic kidney disease.
A more tubulocentric view of diabetic kidney disease.
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DOI：
10.1007/s40620-017-0423-9
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发表时间：
2017-12
影响因子：
3.4
通讯作者：
Unwin RJ
中科院分区：
文献类型：
--
作者：
Zeni L;Norden AGW;Cancarini G;Unwin RJ
糖尿病肾病（DN）是1型和2型糖尿病（DM）的常见并发症，预防终末期肾病（ESRD）仍然是一个重大挑战。尽管DN的发病率很高，但其发病机制仍存在争议。表现为超滤和肾小球大小和电荷选择透过性丧失的初始肾小球疾病可能引发一系列损伤，包括肾小管间质疾病。临床上，尽管越来越多的证据表明其对DN的预测价值值得怀疑，并且研究结果表明近端小管是DN发展中的重要环节，但“微量白蛋白尿”仍然被接受为肾小球损伤的早期生物标志物。“糖尿病肾小管病变”的概念已出现在最近的研究中，其在DN中的致病作用得到了临床和实验证据的支持，以及合理的发病机制。本文综述了DN的“小管中心”观点。最近发现，抑制近端小管（PT）葡萄糖转运（通过SGLT 2）在糖尿病患者中具有肾脏保护作用，讨论了肾小管在DN中的潜在作用。以肾小管为中心的DN研究刺激了早期检测糖尿病肾病的替代临床方法。存在被认为是近端小管（PT）损伤的直接指标的肾小管生物标志物，如N-乙酰-β-D-氨基葡萄糖苷酶、神经胶质酶相关脂质运载蛋白和肾损伤分子-1，以及其他功能性PT生物标志物，如尿游离视黄醇结合蛋白4和胱抑素C，其反映了滤过蛋白的重吸收受损。在需要更好的早期DN生物标志物的背景下，这些测量对糖尿病患者的临床应用将进行审查。
Diabetic nephropathy (DN) is a common complication of Diabetes Mellitus (DM) Types 1 and 2, and prevention of end stage renal disease (ESRD) remains a major challenge. Despite its high prevalence, the pathogenesis of DN is still controversial. Initial glomerular disease manifested by hyperfiltration and loss of glomerular size and charge permselectivity may initiate a cascade of injuries, including tubulo-interstitial disease. Clinically, ‘microalbuminuria’ is still accepted as an early biomarker of glomerular damage, despite mounting evidence that its predictive value for DN is questionable, and findings that suggest the proximal tubule is an important link in the development of DN. The concept of ‘diabetic tubulopathy’ has emerged from recent studies, and its causative role in DN is supported by clinical and experimental evidence, as well as plausible pathogenetic mechanisms. This review explores the ‘tubulocentric’ view of DN. The recent finding that inhibition of proximal tubule (PT) glucose transport (via SGLT2) is nephro-protective in diabetic patients is discussed in relation to the tubule’s potential role in DN. Studies with a tubulocentric view of DN have stimulated alternative clinical approaches to the early detection of diabetic kidney disease. There are tubular biomarkers considered as direct indicators of injury of the proximal tubule (PT), such as N-acetyl-β-D-glucosaminidase, Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1, and other functional PT biomarkers, such as Urine free Retinol-Binding Protein 4 and Cystatin C, which reflect impaired reabsorption of filtered proteins. The clinical application of these measurements to diabetic patients will be reviewed in the context of the need for better biomarkers for early DN.
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