A basis for accelerated progression of diabetic nephropathy in Pima Indians
A basis for accelerated progression of diabetic nephropathy in Pima Indians
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DOI：
10.1046/j.1523-1755.63.s83.9.x
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发表时间：
2003-02-01
影响因子：
19.6
通讯作者：
Lemley, KV
中科院分区：
文献类型：
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作者：
Lemley, KV
亚利桑那州的皮马印第安人不仅因2型糖尿病而患肾病的发病率比白人高得多，而且在患糖尿病肾病后，他们的肾功能也会加速丧失。这种肾功能的快速丧失发生在尽管肾病发病年龄较低、血压和血脂水平较低的情况下，所有这些似乎都预示着肾病进展速度较慢。这些发现表明，其他因素有助于该人群中肾脏疾病的快速进展。特别是，该人群中的肾小球肥大可能导致终末期临床表现阶段肾小球滤过率（GFR）损失率较高，因为硬化导致每个肾单位损失的单肾单位GFR（SNGFR）损失增量更大。在9名患有2型糖尿病肾病的皮马印第安人中，我们检查了初始活检时肾小球簇体积与终末期GFR损失率之间的关系，这些患者接受了长达10年的肾活检，随后进行了连续的碘酞酸清除。通过多变量分析，肾小球体积（P=0.006）和足细胞密度（P=0.043）的显着独立影响在这些个体中是明显的。肾小球体积的影响可能是由于每个肾小球损失的内在过滤能力的更大损失，而足细胞密度的影响可能反映了“足细胞不足”对肾小球簇的不稳定影响。在肾小球肥大和肾小球硬化并存的其他土著人群中，类似的因素可能在与进行性肾小球疾病相关的GFR快速丧失中发挥作用。
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.