Levine David Z
Division of Nephrology, Kidney Research Centre, Ottawa Hospital and University of Ottawa, Toronto, ON, Canada.
Clin Sci (Lond). 2008 Jan;114(2):109-18. doi: 10.1042/CS20070088.
In the past, hyperfiltration and increased glomerular capillary pressure have been identified as important determinants of the development of DN (diabetic nephropathy). Recently, some basic research and clinical reviews on DN have omitted identifying hyperfiltration as an important risk factor. At the same time, different rodent models of DN have been described without and with documented hyperfiltration. In the present review, the importance of hyperfiltration is reassessed, reviewing key clinical and research studies, including the first single nephron studies in a mouse model of DN. From clinical studies of Type 1 and Type 2 diabetes mellitus, it is clear that many patients do not have early hyperfiltration and, even when present, its contribution to subsequent DN remains uncertain. Key mechanisms underlying hyperfiltration in rodent models are reviewed. Findings on intrarenal NO metabolism and the control of single-nephron GFR (glomerular filtration rate) in rodent models of DN are also presented. Characterization of valid experimental models of DN should include a careful delineation of the absence or presence of early hyperfiltration, with special efforts made to establish the specific role hyperfiltration may play in the emergence of DN.
过去，超滤和肾小球毛细血管压力升高已被确定为糖尿病肾病（DN）发生发展的重要决定因素。最近，一些关于DN的基础研究和临床综述未将超滤视为重要危险因素。与此同时，已描述了有无超滤记录的不同DN啮齿动物模型。在本综述中，重新评估了超滤的重要性，回顾了关键的临床和研究，包括在DN小鼠模型中的首次单肾单位研究。从1型和2型糖尿病的临床研究来看，很明显许多患者没有早期超滤，即使存在超滤，其对后续DN的影响仍不确定。本文回顾了啮齿动物模型中超滤的关键机制。还介绍了DN啮齿动物模型中肾内一氧化氮代谢和单肾单位肾小球滤过率（GFR）控制的研究结果。有效的DN实验模型的特征应包括仔细描述早期超滤的有无，并特别努力确定超滤在DN发生中可能发挥的具体作用。
