Systemic factors are involved in the pathogenesis of proteinuria-induced glomerulosclerosis in adriamycin nephrotic rats

This study aims to dissociate the respective roles of systemic nephrosis an d of the intrarenal effects of proteinuria in the pathogenesis of focal seg mental glomerulosclerosis (FCS) in adriamycin nephrosis. To this purpose, t his study examined proteinuria and FGS in bilateral (BAP) and unilateral pr oteinuria (UAP) in two different rat strains. UAP was obtained by protectin g one kidney from exposure to adriamycin by temporary clipping of one renal artery during adriamycin injection. At sacrifice (week 12), FGS was presen t in BAP and in exposed kidneys in UAP, but not in unexposed kidneys. PGS c orrelated significantly with proteinuria per kidney in BAP and UAP. Remarka bly, for a given proteinuria per kidney, the sclerosis score was higher in BAP than in UAP, reflected by a higher ratio of FGS score per mg proteinuri a per kidney (Wistar: 0.09 +/- 0.01 in BAP versus 0.05 +/- 0.01%/mg protein per d in UAP, P < 0.05; Lewis: 0.12 +/- 0.01 in BAP versus 0.07 +/- 0.01 % /mg protein per d in UAP, P < 0.05), indicating that the local damaging eff ects of proteinuria are modified by other factors. Cholesterol correlated w ith total proteinuria in BAP and UAP. FCS score was positively correlated w ith cholesterol. The latter correlation was similar in BAP and UAP, indicat ing that cholesterol was a more uniform predictor for FGS than proteinuria per kidney. This was independent of strain-specific factors. On multilinear regression analysis, cholesterol turned out to be the most consistent pred ictor of FGS in proteinuric kidneys, with a stronger predictive value than proteinuria per kidney. It is concluded that although systemic sequelae of nephrosis do not induce renal damage in nonproteinuric kidneys, they modify the severity of proteinuria-induced FGS in proteinuric kidneys.