Glomerular permselectivity in early stages of overt diabetic nephropathy.
Glomerular permselectivity in early stages of overt diabetic nephropathy.
复制标题
明显糖尿病肾病早期的肾小球通透性选择性。
DOI：
10.1111/j.1523-1755.2000.00386.x
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Myers,BD
中科院分区：
文献类型：
--
作者：
Andersen,S;Blouch,K;Bialek,J;Deckert,M;Parving,HH;Myers,BD
Glomerular permselectivity in early stages of overt diabetic nephropathy.BackgroundImpairment of glomerular size selectivity has been demonstrated by the dextran-sieving technique in nephropathic diabetics with heavy, but not mild proteinuria. The purpose of the present study was to determine whether such a barrier defect could be demonstrated with mild proteinuria by substituting Ficoll 70, a polysucrose, for dextran as a probe of the filtration barrier.MethodsDifferential solute clearances were performed in 12 individuals with early diabetic nephropathy on two occasions: after 60 days of treatment with losartan 50 mg daily or a placebo. An uncharged preparation of nonreabsorbable Ficoll 70 was infused along with inulin. Fractional clearance (θ) of Ficoll of discrete size was determined after separating molecules in urine and plasma in narrow 2 Å fractions over a 20 to 60 Å radius interval by size exclusion high-performance liquid chromatography (HPLC). A hydrodynamic theory of hindered ficoll transport through water-filled pores was used to characterize the pore size distribution of the glomerular barrier.ResultsThe θ for Ficoll molecules with radii> 50 Å was selectively enhanced in placebo-treated diabetic nephropathy versus corresponding θ in healthy control subjects (N= 12). Computations revealed a lower distribution of glomerular pores that was unaltered in nephropathic diabetics. However, an upper distribution of large, shunt-like pores was more prominent, exceeding healthy controls by one order of magnitude in diabetic nephropathy (P= 0.01). A trend to lower θ for Ficoll in the 56 to 60 Å radius range during losartan therapy is computed to have lowered the fraction of shunted filtrate by 26 to 44%, depending on whether glomerular pressure declined. The corresponding reduction in θ for endogenous albumin, IgG, and IgG4was by 19 to 23% (P< 0.05).ConclusionOur findings suggest that shunt-like defects, partially reversible by angiotensin II blockade, are present early in the course of diabetic nephropathy. We estimate that such defects can account for immunoglobulinuria in this disorder. Additional impairment of either charge- or shape-selectivity must be invoked to explain the observed level of albuminuria, however.
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血管紧张素 II 受体阻断对实验性糖尿病大鼠的短期和长期影响。
影响因子：
13.6
作者：
A. Remuzzi;N. Perico;C. Amuchastegui;B. Malanchini;M. Mazerska;C. Battaglia;T. Bertani;G. Remuzzi
通讯作者：
G. Remuzzi
前蛋白尿和蛋白尿糖尿病大鼠的肾小球滤过和肾小管白蛋白重吸收。
DOI：
10.1172/jci116638
发表时间：
1993
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Tucker,BJ;Rasch,R;Blantz,RC
通讯作者：
Blantz,RC
健康和肾病人类的分子构型和肾小球大小选择性。
DOI：
10.1152/ajprenal.1997.273.3.f430
发表时间：
1997
期刊：
The American journal of physiology.
影响因子：
--
作者：
Blouch,K;Deen,WM;Fauvel,JP;Bialek,J;Derby,G;Myers,BD
通讯作者：
Myers,BD
肾小管摄取蛋白质：分子电荷的影响。
DOI：
10.1152/ajprenal.1983.244.4.f436
发表时间：
1983
期刊：
The American journal of physiology
影响因子：
--
作者：
Christensen,EI;Rennke,HG;Carone,FA
通讯作者：
Carone,FA
DOI：
10.1152/ajprenal.1981.241.2.f162
发表时间：
1981-08
期刊：
The American journal of physiology
影响因子：
--
作者：
W. Deen;B. Satvat
通讯作者：
W. Deen;B. Satvat