Renal effects of moderate hypercholesterolaemia in uninephrectomized rats.

Abstract

Animal studies have shown that a 4-6-fold increase in serum cholesterol aggravates pre-existing renal injury. We studied the renal effects of moderate hypercholesterolaemia over a period of 18 weeks in uninephrectomized rats. Animals were allocated to two groups; the group 1 rats were fed a normal diet, as controls, and the group 2 rats were fed a high cholesterol diet containing 3% cholesterol and 1% sodium cholate by weight. The serum total cholesterol was higher in group 2 than in controls being 2.5 +/- 0.4 vs. 1.0 +/- 0.1 mmol l-1 at 9 weeks and 2.1 +/- 0.3 vs. 1.1 +/- 0.2 mmol l-1 at 18 weeks (p < 0.05 for both). Serum high density lipoprotein cholesterol levels were similar in both groups. The mean systolic blood pressure was higher in group 2 than in controls, at 145 +/- 9 vs. 137 +/- 8 mmHg (p < 0.05) by 13 weeks and 146 +/- 6 vs. 136 +/- 4 mmHg (p < 0.05) at 18 weeks. Serum creatinine and glomerular filtration rates were similar in both groups. Urine protein excretion remained within the normal range in both groups. Histological examination at 18 weeks showed diffuse fatty changes in the liver cells and prominent vacuolization of renal tubule cells in the group 2 rats. Nevertheless, the glomeruli were normal. There was no significant difference in mean glomerular volume between group 2 rats (1.20(-3) +/- 0.09(-3) mm3) and controls (1.36(-3) +/- 0.10(-3) mm3). Thus moderate hypercholesterolaemia for 18 weeks in uninephrectomized rats resulted in a mild elevation in blood pressure, but did not affect glomerular volume or glomerular histology, in spite of the deleterious effects on liver and renal tubule cells. We assume that extremely high levels of serum cholesterol are required to induce glomerulosclerosis in the rat.