Brito P L, Fioretto P, Drummond K, Kim Y, Steffes M W, Basgen J M, Sisson-Ross S, Mauer M
Department of Pediatrics, University of Minnesota, Minneapolis, USA.
Kidney Int. 1998 Mar;53(3):754-61. doi: 10.1046/j.1523-1755.1998.00809.x.
Although glomerular structure has been studied, careful evaluation of tubular basement membrane (TBM) structure in diabetes in humans has not been done. We measured proximal TBM width, glomerular basement membrane (GBM) width, mesangial fractional volume [Vv(Mes/glom)], mesangial matrix fractional volume [Vv(MM/glom)], and cortical interstitial fractional volume [Vv(Int/cortex)] in 35 insulin-dependent diabetic (IDDM) patients and 20 controls. The patients' mean age was 28 +/- 10 years (X +/- SD) and IDDM duration was 17 +/- 8 years. Twenty-five patients were normoalbuminuric, four microalbuminuric, and six had overt proteinuria. Tubular basement membrane and GBM widths were measured by the orthogonal intercept method and mesangial and interstitial parameters by point counting. The TBM width was 915 +/- 320 nm in IDDM patients and 558 +/- 116 nm in controls (P = 0.0005); the TBM width was also increased in normoalbuminuric patients (849 +/- 297 nm, P = 0.0005). The TBM width was strongly directly related to GBM width (r = 0.67, P < 0.001), Vv(Mes/glom) (r = 0.52, P < 0.01), and Vv(MM/glom) (r = 0.61, P < 0.001), but only weakly to Vv(Int/cortex) (r = 0.29, NS). The TBM width (r = 0.65, P < 0.001) and GBM width (r = 0.65, P < 0.001) were strongly related to hemoglobin A1C (HbA1C), while the Vv(Mes/glom) (r = 0.35, P < 0.05) and Vv(Int/cortex) (r = 0.30, NS) were only weakly related to HbA1C. Thus, increased proximal TBM width is an integral component of early nephropathology in IDDM patients. This study suggests that the metabolic disturbances of diabetes are strong determinants of the constellation of structural abnormalities occurring in human diabetic nephropathy.
尽管肾小球结构已得到研究，但尚未对人类糖尿病患者的肾小管基底膜（TBM）结构进行仔细评估。我们测量了35例胰岛素依赖型糖尿病（IDDM）患者和20例对照者的近端TBM宽度、肾小球基底膜（GBM）宽度、系膜分数体积[Vv（Mes/glom）]、系膜基质分数体积[Vv（MM/glom）]和皮质间质分数体积[Vv（Int/cortex）]。患者的平均年龄为28±10岁（X±SD），IDDM病程为17±8年。25例患者为正常白蛋白尿，4例为微量白蛋白尿，6例有显性蛋白尿。通过正交截距法测量肾小管基底膜和GBM宽度，通过点计数法测量系膜和间质参数。IDDM患者的TBM宽度为915±320nm，对照者为558±116nm（P = 0.0005）；正常白蛋白尿患者的TBM宽度也增加（849±297nm，P = 0.0005）。TBM宽度与GBM宽度（r = 0.67，P < 0.001）、Vv（Mes/glom）（r = 0.52，P < 0.01）和Vv（MM/glom）（r = 0.61，P < 0.001）密切正相关，但与Vv（Int/cortex）仅呈弱相关（r = 0.29，无显著性差异）。TBM宽度（r = 0.65，P < 0.001）和GBM宽度（r = 0.65，P < 0.001）与糖化血红蛋白（HbA1C）密切相关，而Vv（Mes/glom）（r = 0.35，P < 0.05）和Vv（Int/cortex）（r = 0.30，无显著性差异）与HbA1C仅呈弱相关。因此，近端TBM宽度增加是IDDM患者早期肾病的一个重要组成部分。本研究表明，糖尿病的代谢紊乱是人类糖尿病肾病中发生的一系列结构异常的重要决定因素。
