The role of lipids in the pathogenesis of glomerulosclerosis in the rat following subtotal nephrectomy

Abstract. Similarities between atherosclerosis and glomerulosclerosis suggest that hyperlipidaemia may contribute to glomerular injury. Dietary supplementation with 4% cholesterol +1% cholic acid was administered to rats 4 weeks after 1 1/3 nephrectomy and continued for 7 weeks. There was a significant increase in serum cholesterol (peak= 11.52 ±1.09 mmol 1^-1 vs. 4.73 ± 0.31 on control diet, < 0.001) and triglyceride concentrations (peak = 2.31 ± 0.27 mmol 1^-1 vs. 1.41 ±0.29, <0.05) and a marked increase in βmigrating lipoproteins. The severity of hypercholester-olaemia was significantly correlated with proteinuria (control diet: r = 0.600, cholesterol diet: r = 0.672, < 0.0001) as was hypertriglyceridaemia (control diet: r = 0.544, cholesterol diet: r = 0.678, <0.0001). The percentage of glomeruli containing lipid deposits was increased from 21% to 60% (<0.05). The kidney total cholesterol content was increased from 29.2 ±0.8 to 47.7 ± 3.3 μmols g^-1 dry weight (<0.0001), with esterified cholesterol increasing from 7.5 ± 0.4% to 14.5 ± 2.1% of total (<0.01). Serum cholesterol concentration was significantly correlated with both glomerular lipid deposition ( r _s= 0.7195, <0.0001) and tissue total cholesterol content ( r _s= 0.6053, <0.001). Lipid vacuolation was prominent in the paramesangium and within mesangial cells. Despite these changes hypertension, uraemia, proteinuria and glomerulosclerosis were not significantly increased on the cholesterol diet. Cholesterol deposition in the glomeruli occurs secondary to hyperlipidaemia in rats following subtotal nephrectomy but over 7 weeks no exacerbation of glomerulosclerosis is detectable.