Interstitial foam cells and oxidized lipoprotein in human glomerular disease

Foam cells (FCs) have been detected in the cortical interstitium of some patients with glomerular disease. Whether they have a significant role in tubulointerstitial injury and disease progression is uncertain. Renal biopsy specimens from 13 patients with glomerular disease (6 with Alport's syndrome, 5 with focal glomerulosclerosis, 2 with membranoproliferative glomerulonephritis, Type 1) showing interstitial FCs were investigated by histochemical means for neutral lipid (oil red O stain); immunohistochemical means for monocytes/macrophages (CD68), apolipoproteins (Apo) A-I, B, and E, and oxidized low-density lipoprotein (LDL); and by electron microscopic examination. FCs were positive for neutral lipid, CD68, and oxidized lipoprotein but did not stain for Apo B. In four specimens, there was a weak FC reaction for Apo E alone and in one case for both Apo E and Apo A-I. Focal interstitial staining was observed for both Apo B and E but not for Apo A-I. There was focal staining of tubular epithelial cytoplasm for neutral lipid in all of the specimens, for Apo E in five of seven specimens, for oxidized lipoprotein in case, and for Apo A-I in three cases. Electron microscopic analysis showed that the FC contained numerous clear cytoplasmic vacuoles that were not membrane-bound and that were generally associated with increased numbers of collagen fibrils and basement membrane-like extracellular matrix and frequently with aggregates of extracellular lipid-like particles embedded in extracellular matrix. The findings are analogous to those in atherosclerosis and suggest a role for FCs and oxidized lipoprotein in the pathogenesis of interstitial injury in some cases of glomerular disease.