EFFECTS OF HYPERCHOLESTEROLEMIA ON INITIAL AND CHRONIC PHASES OF RAT NEPHROTOXIC SERUM NEPHRITIS - DEVELOPMENT OF FOCAL SEGMENTAL GLOMERULOSCLEROSIS, ANALOGOUS TO ATHEROSCLEROSIS

The effects of hypercholesterolemia on both the initial and chronic phases of rat nephrotoxic serum (NTS) nephritis have been investigated. Injury during the initial phase of NTS nephritis in hypercholesterolemic rats maintained on a cholesterol-supplemented diet (Group 2) was characterized by segmentally accentuated accumulations of vacuolated cells with lipid droplets (foam cells) in the glomeruli, while the kidneys of rats fed a standard diet (Group 1) revealed only mild intracapillary cell proliferation. Immunoelectron microscopy showed that the foam cells observed in Group 2 rats were largely derived from macrophages. The glomerular macrophage number, defined by the number of ED1-positive cells per glomerulus, was significantly higher in Group 2 than in Group 1 animals at days 5-6 (3.4 +/- 1.4 in Group 1 against 6.3 +/- 1.0 in Group 2; p < 0.01) as well as at days 21-28 (5.5 +/- 2.6 in Group 1 against 10.9 +/- 2.8 in Group 2; p<0.01). In contrast, the numbers of OX19-positive T-lymphocytes and OX33-positive B-lymphocytes were similar in both groups. In the chronic phase of NTS nephritis at week 20, semiquantitative evaluation of the glomerular lesions disclosed more severe focal segmental glomerulosclerosis (FSGS) in Group 2 compared with Group 1 animals (glomerular injury score: 14 +/- 10 in Group 1 against 73 +/- 17 in Group 2; p < 0.01). Accumulations of lipid and foam cells were invariably seen in the sclerotic foci of Group 2 animals. The results indicate that hypercholesterolemia played an important role in the accelerated development of FSGS in rat NTS nephritis. The presence of lipid and the augmented influx of macrophages (foam cells) have close parallel with atherosclerosis and suggest that analogous pathogenetic mechanisms may be at work.