Cholesterol feeding following unilateral nephrectomy in the rat leads to glomerular hypertrophy

Experimental glomerulosclerosis is associated with hyperlipidaemia and the deposition of lipid in glomeruli. Glomerulosclerosis is typically preceded by glomerular hypertrophy. To investigate a possible pathogenic role of lipids in glomerulosclerosis, glomerular structure and cellular composition were studied in rats fed either a control diet or one supplemented with 4% cholesterol and 1% cholic acid for 21 weeks following unilateral nephrectomy. On the cholesterol diet there were significant increases in glomerular cross-sectional area (13.11 +/- 0.39 x 10(3) vs. 11.13 +/- 0.44 x 10(3) mu 2, p less than 0.01) and mesangial area (1.81 +/- 0.07 x 10(3) vs. 1.50 +/- 0.08 x 10(3) mu 2, p less than 0.02). These changes were significantly correlated with proteinuria, which was significantly greater on the cholesterol diet (mean area under curve for duration of diet = 3.11 +/- 0.38 vs. 1.42 +/- 0.35 g, p less than 0.02). There was a significant increase in glomerular leukocytes on the cholesterol diet (4.10 +/- 0.44 vs 2.86 +/- 0.25 OX-1 positive cells/10(4) mu 2, p less than 0.05). Mesangial foam cells, derived from macrophages, were associated with adhesions to Bowman's capsule. These results demonstrate that hyperlipidaemia exacerbates the development of glomerular hypertrophy and that this may be mediated by factors released during the phagocytosis of lipoprotein deposits by macrophages.