Local macrophage proliferation in human glomerulonephritis

Abstract

Background: Local macrophage proliferation has been described in several animal models of glomerulonephritis (GN), but its significance in human disease is unknown.

Methods: Double immunostaining for CD68 and the proliferating cell nuclear antigen (PCNA) was used to identify macrophage proliferation in 84 biopsies from a variety of glomerulonephridities.

Results: A small resident population of glomerular and interstitial CD68+ macrophages was identified in normal human kidney, of which only 1 to 2% showed evidence of proliferation on the basis of PCNA expression. A mild macrophage infiltrate, with only occasional proliferating macrophages, was seen in the less aggressive forms of GN (minimal change disease, non-IgA mesangioproliferative GN and IgA nephropathy). This was in sharp contrast to the more aggressive forms of disease (lupus class IV, vasculitis-associated GN, crescentic GN and mesangiocapillary proliferative GN), in which the prominent macrophage infiltrates contained many proliferating macrophages, accounting for 28 to 47% of the total macrophage population. Macrophage proliferation was largely restricted to areas of severe tissue damage (glomerular segmental proliferative lesions, crescents and foci of tubulointerstitial damage), suggesting that local proliferation is a mechanism for amplifying macrophage-mediated injury. Glomerular and interstitial macrophage proliferation gave a significant correlation with loss of renal function (P < 0.0001) and histologic lesions (P < 0.0001), but not with proteinuria. Interstitial T-cell proliferation also gave a significant correlation with loss of renal function and histologic damage, even though proliferation within the T-cell population was much lower than in the macrophage population.

Conclusions: This study demonstrates that macrophage proliferation is a feature of the more aggressive forms of human GN. Local proliferation may be an important mechanism for amplifying macrophage-mediated renal injury. In addition, the degree of local macrophage proliferation may be a useful diagnostic and prognostic indicator for human GN.