Interstitial nephritis induced by protein-overload proteinuria.

作者：Allison A. Eddy · 发表于：PubMed · 年份：1989 · 被引用次数：288 · 研究领域：Renal function and acid-base balance、Ion Transport and Channel Regulation、Liver Disease and Transplantation

Experimental nephrotic syndrome induced by several immunologic and biochemical methods is associated with the development of tubulointerstitial nephritis (TIN). To investigate the hypothesis that severe sustained proteinuria plays a role in the pathogenesis of TIN, the renal interstitium in a model of protein-overload proteinuria was studied. After uninephrectomy, rats received daily injections of 1.0 g of bovine serum albumin (BSA) or saline (controls) until killing at 1, 2, 4, or 7 weeks. Sections of frozen renal cortex were stained with a panel of monoclonal antibodies reactive with subsets of rat lymphohemopoietic cells, and positive tubulointerstitial cells (TIC) were quantitated by epifluorescence microscopy. BSA rats developed proteinuria, with mean rat urinary albumin excretion rates at 1, 2, 3, and 6 weeks of 35.6 +/- 21.8, 97.2 +/- 46.1, 63.6 +/- 40.8, and 58.6 +/- 24.4 mg/24 hours, respectively (controls, 0.17 +/- 0.16 mg/24 hours). BSA was detectable in the plasma of experimental animals at all periods, with mean values of 26.8 +/- 3.8, 27.8 +/- 2.7, 20.3 +/- 6.2, and 7.0 +/- 1.1 mg/ml (controls, 0.03 +/- 0.04 mg/ml) at 1, 2, 4, and 7 weeks, respectively, whereas plasma anti-BSA antibodies were never detected. A significant mononuclear cell infiltrate was present in the interstitium of experimental animals at all periods. At 1 week, an influx of macrophages was evident that was identified by surface markers OX42 (75+/1000 TIC) (P less than 0.01) and Ia (58+/1000 T...