title: Systemic factors are involved in the pathogenesis of proteinuria-induced glomerulosclerosis in adriamycin nephrotic rats.
abstract: This study aims to dissociate the respective roles of systemic nephrosis and of the intrarenal effects of proteinuria in the pathogenesis of focal segmental glomerulosclerosis (FGS) in adriamycin nephrosis. To this purpose, this study examined proteinuria and FGS in bilateral (BAP) and unilateral proteinuria (UAP) in two different rat strains. UAP was obtained by protecting one kidney from exposure to adriamycin by temporary clipping of one renal artery during adriamycin injection. At sacrifice (week 12), FGS was present in BAP and in exposed kidneys in UAP, but not in unexposed kidneys. FGS correlated significantly with proteinuria per kidney in BAP and UAP. Remarkably, 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 proteinuria 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 effects of proteinuria are modified by other factors. Cholesterol correlated with total proteinuria in BAP and UAP. FGS score was positively correlated with cholesterol. The latter correlation was similar in BAP and UAP, indicating 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 predictor 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.
authors.affiliation: Department of Nephrology, Groningen Institute for Drug Studies, State University Hospital, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: De Boer
authors.forename: G
authors.initials: G
authors.lastname: Navis
authors.forename: A T
authors.initials: AT
authors.lastname: Tiebosch
authors.forename: P E
authors.initials: PE
authors.lastname: De Jong
authors.forename: D
authors.initials: D
authors.lastname: De Zeeuw
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D002784:Cholesterol / Q000097:blood; D004317:Doxorubicin / Q000633:toxicity*; D005919:Glomerular Filtration Rate; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology*; D008297:Male; D011507:Proteinuria / Q000150:complications*; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D013045:Species Specificity
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D002784:Cholesterol