PLASMA-LIPOPROTEINS AND RENAL APOLIPOPROTEINS IN RATS WITH CHRONIC ADRIAMYCIN NEPHROSIS

The relation between plasma lipoprotein composition and renal apolipop rotein deposition was studied in nephrotic rats in which stable renal function had been monitored for 7 months after a single low dose of ad riamycin (ADR, 3 mg/kg). Proteinuria was observed 3 weeks after ADR an d 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 a t about 80% of control values. Hypercholesterolaemia was observed 6 we eks after ADR, and increased progressively up to 7.0 +/- 1.0 mmol/l (v ersus 2.3 +/- 0.1 mmol/l in controls; P < 0.001). Cholesterol was prim arily located in LDL2 and HDL2 lipoproteins. Plasma apolipoprotein (ap o) A-I increased by more than 400% in the nephrotic rats (P < 0.001). Apo B and apo E increased by about 60% (P < 0.01), whereas apo A-IV re mained unchanged. Focal sclerotic lesions in glomeruli had an incidenc e of 50 +/- 10% in ADR rats versus 2 +/- 1% in controls (P < 0.001). I mmunohistochemistry revealed apo A-I and apo A-IV in the visceral epit helium. Apo E immunoreactivity and lipid deposits were observed in foc al glomerular sclerotic lesions of ADR rats. Neither apolipoproteins n or lipids were detected in glomeruli of controls. Proximal tubular loc alization of apolipoproteins was extensive for apo A-I, apo A-IV and a po E, but no differences were observed in tubular deposition of apolip oproteins between ADR and control rats. Chronic proteinuria induced by a single low dose of ADR in rats is a promising model to study the al leged pathogenetic role of hyperlipidaemia in relation to mesangial ap olipoprotein E and lipid deposition in the deterioration of renal func tion and morphology in the nephrotic syndrome.