Lemley Kevin V
Division of Pediatric Nephrology, Stanford University School of Medicine, Stanford, California 94305, USA.
Kidney Int Suppl. 2003 Feb(83):S38-42. doi: 10.1046/j.1523-1755.63.s83.9.x.
The Pima Indians of Arizona not only have a much higher incidence of nephropathy due to type 2 diabetes than Caucasians, but they also lose their renal function at an accelerated rate after they develop diabetic nephropathy. This rapid loss of renal function occurs despite a younger age of onset of nephropathy and lower blood pressures and lipid levels, all of which would seem to predict a slower rate of progression of nephropathy. These findings suggest that other factors contribute to the rapid progression of renal disease in this population. In particular, glomerulomegaly in this population may contribute to the high rate of glomerular filtration rate (GFR) loss during the terminal, clinically manifest phase of nephropathy, because of the greater incremental loss of single-nephron GFR (SNGFR) with each nephron lost to sclerosis. In nine Pima Indians with type 2 diabetic nephropathy who underwent renal biopsy followed by serial iothalamate clearances for up to ten years, we examined the relationship between glomerular tuft volume at initial biopsy and the rate of GFR loss during the terminal phase. By multivariate analysis, significant independent effects of both glomerular volume (P=0.006) and podocyte density (P=0.043) were evident in these individuals. The effect of glomerular volume may result from a greater loss of intrinsic filtration capacity with each glomerulus lost, while the effect of podocyte density may reflect the destabilizing influence of "podocyte insufficiency" on the glomerular tuft. Similar factors may play a role in the rapid loss of GFR associated with progressive glomerular diseases in other indigenous populations in whom glomerulomegaly and glomerulopenia coexist.
亚利桑那州的皮马印第安人不仅患2型糖尿病肾病的发病率比白种人高得多，而且在患糖尿病肾病后，他们的肾功能丧失速度也更快。尽管肾病发病年龄较轻、血压和血脂水平较低，但肾功能仍迅速丧失，而这些因素似乎都预示着肾病进展速度会较慢。这些发现表明，其他因素导致了该人群肾病的快速进展。特别是，该人群中的肾小球肥大可能导致肾病终末期临床症状明显阶段肾小球滤过率（GFR）快速下降，因为随着每个肾小球因硬化而丧失，单个肾单位GFR（SNGFR）的增量损失更大。在9名患有2型糖尿病肾病的皮马印第安人身上，我们先进行了肾活检，随后连续10年进行碘他拉酸盐清除率检测，研究了初次活检时肾小球体积与终末期GFR下降速率之间的关系。通过多变量分析，在这些个体中，肾小球体积（P = 0.006）和足细胞密度（P = 0.043）均有显著的独立影响。肾小球体积的影响可能是由于每个丧失的肾小球内在滤过能力损失更大，而足细胞密度的影响可能反映了“足细胞不足”对肾小球的不稳定影响。类似的因素可能在其他同时存在肾小球肥大和肾小球减少的原住民人群中，与进行性肾小球疾病相关的GFR快速下降中起作用。
