Myers B D, Nelson R G, Williams G W, Bennett P H, Hardy S A, Berg R L, Loon N, Knowler W C, Mitch W E
Division of Nephrology, Stanford University School of Medicine, California 94305.
J Clin Invest. 1991 Aug;88(2):524-30. doi: 10.1172/JCI115335.
Differential solute clearances were used to characterize glomerular function in 20 Pima Indians with noninsulin-dependent diabetes mellitus (NIDDM) of less than 3 yr duration. 28 Pima Indians with normal glucose tolerance served as controls. In the diabetic group, the glomerular filtration rate (GFR, iothalamate clearance) exceeded the control value by 15% (140 +/- 6 vs. 122 +/- 5 ml/min, P less than 0.01). A corresponding 12% increase in renal plasma flow (RPF) was not statistically significant and did not account fully for the observed hyperfiltration, suggesting a concomitant elevation of the ultrafiltration pressure or coefficient. The median albumin excretion ratio in NIDDM exceeded control by almost twofold (10.1 vs. 5.8 mg/g creatinine), a trend which just failed to achieve statistical significance (P = 0.06). Fractional clearances of dextrans of broad size distribution were also elevated in diabetic subjects, significantly so for larger dextrans of between 48 and 60 A radius. A theoretical analysis of dextran transport through a heteroporous membrane revealed glomerular pores in NIDDM to be uniformly shifted towards pores of larger size than in controls. We conclude that an impairment of barrier size selectivity combined with high GFR elevates the filtered protein load in NIDDM of recent onset. We propose that enhanced transglomerular trafficking of protein may predispose to sclerosis of glomeruli in those Pima Indians with NIDDM who ultimately develop diabetic nephropathy.
采用不同溶质清除率来表征20名病程小于3年的皮马族非胰岛素依赖型糖尿病（NIDDM）印第安人的肾小球功能。28名糖耐量正常的皮马族印第安人作为对照。糖尿病组的肾小球滤过率（GFR，碘肽酸盐清除率）比对照组高15%（140±6对122±5 ml/min，P<0.01）。肾血浆流量（RPF）相应增加12%，但无统计学意义，且不能完全解释观察到的超滤过现象，提示超滤压或超滤系数同时升高。NIDDM患者的白蛋白排泄率中位数比对照组高出近两倍（10.1对5.8 mg/g肌酐），这一趋势未能达到统计学意义（P = 0.06）。糖尿病患者中宽分子量分布葡聚糖的分数清除率也升高，对于半径在48至60 Å之间的较大葡聚糖，升高具有显著性。对葡聚糖通过异孔膜转运的理论分析表明，NIDDM患者的肾小球孔比对照组均匀地向更大尺寸的孔偏移。我们得出结论，屏障大小选择性受损与高GFR相结合，会增加近期发病的NIDDM患者的滤过蛋白负荷。我们提出，在最终发生糖尿病肾病的NIDDM皮马族印第安人中，增强的跨肾小球蛋白转运可能易导致肾小球硬化。
