Plasma lipoproteins and renal apolipoproteins in rats with chronic adriamycin nephrosis

The relation between plasma lipoprotein composition and renal apolipoprotein deposition was studied in nephrotic rats in which stable renal function had been monitored for 7 months after a single low dose of adriamycin (ADR, 3 mg/kg). Proteinuria was observed 3 weeks after ADR and increased progressively up to about 0.5 g/day (versus 0.07 g/day in controls; P< 0.001), while the creatinine clearance remained stable at about 80% of control values. Hypercholesterolaemia was observed 6 weeks after ADR, and increased progressively up to 7.0±1.0 mmol/l (versus 2.3±0.1 mmol/l in controls; P<0.001). Cholesterol was primarily located in LDL2 and HDL2 lipoproteins. Plasma apolipoprotein (apo) A-I increased by more than 400% in the nephrotic rats (/><0.001). Apo B and apo E increased by about 60% (P<0.01), whereas apo A-IV remained unchanged. Focal sclerotic lesions in glomeruli had an incidence of 50±10% in ADR rats versus 2±1% in controls (P<0.001). Immunohistochemistry revealed apo A-I and apo A-IV in the visceral epithelium. Apo E immunoreactivity and lipid deposits were observed in focal glomerular sclerotic lesions of ADR rats. Neither apolipoproteins nor lipids were detected in glomeruli of controls. Proximal tubular localization of apolipoproteins was extensive for apo A-I, apo A-IV and apo E, but no differences were observed in tubular deposition of apolipoproteins between ADR and control rats. Chronic proteinuria induced by a single low dose of ADR in rats is a promising model to study the alleged pathogenetic role of hyperlipidaemia in relation to mesangial apolipoprotein E and lipid deposition in the deterioration of renal function and morphology in the nephrotic syndrome.