Clinicopathological characteristics of interstitial foam cells in membranous nephropathy

Background. Interstitial foam cells are occasionally observed in various re nal diseases, and they have been reported to belong to the monocyte/macroph age (M phi) lineage and to be associated with heavy proteinuria and hyperli pidemia. We investigated the characteristics of interstitial foam cells and their association with proteinuria and hyperlipidemia in idiopathic membra nous nephropathy (MN). Methods. Patients with MN (N = 320) were divided into two groups: group I c onsisted of 51 patients with interstitial foam cells, and group II consiste d of the other 269 without foam cells. We compared clinical parameters and the findings of an immunohistochemical study using monoclonal antibodies to various types of leukocytes and adhesion molecules. Results. The age at renal biopsy, the degree of proteinuria, serum levels o f lipids, and other clinical parameters except for sex ratio were not diffe rent between the two groups. The ratio of nephrotic patients was compatible between groups I (56.9%) and II (52.8%). All interstitial foam cells were positive for CD68 and 25F9, which are markers for MO and mature M phi, resp ectively, but were negative for CD3 or cytokeratin. Interstitial infiltrati ng cells were positive for CD68 and CD3 but were negative for 25F9. Further more. most of interstitial foam cells were positive for both leukocyte func tion associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (IC AM-1), but not for ICAM-3 (the third ligand for LFA-1). By contrast, most o f infiltrating nonfoamy M phi s were positive for ICAM-3 and LFA-1. however , ICAM-1 was observed on only some of them. Conclusion. These results suggest that interstitial foam cells in MN may no t depend on proteinuria nor hyperlipidemia directly, The accumulation of fo am cells, which have characteristics of mature M phi, may be related to ICA M-1 as a ligand of LFA-1, whereas infiltration of nonfoamy M phi s has a cl ose relationship with ICAM-3. Thus, the formation of interstitial foam cell s may be related to the phenotypical transformation of M phi s.