Lupus Podocytopathy: An Overview

Abstract

In systemic lupus erythematosus, nephrotic-range proteinuria typically signals the presence of a proliferative lupus nephritis (class III/IV) and/or membranous lupus nephritis (class V, with or without concomitant class III or IV lesions). However, in rare instances, systemic lupus erythematosus patients with nephrotic syndrome have kidney biopsy findings of normal glomeruli or focal segmental glomerulosclerosis lesions, with or without mesangial proliferation, on light microscopy; the absence of subepithelial or subendothelial deposits on immunofluorescence and electron microscopy; and diffuse foot process effacement on electron microscopy. This pattern, termed lupus podocytopathy, is a unique form of lupus nephritis that mimics minimal change disease or primary focal segmental glomerulosclerosis and represents approximately 1% of lupus nephritis biopsies. Here we review the clinical features, histological manifestations, diagnostic criteria and classification, pathogenesis, treatment, and prognosis of lupus podocytopathy.

Keywords: Focal segmental glomerulosclerosis; Lupus nephritis; Lupus podocytopathy; Minimal change disease; Systemic lupus erythematosus.

Figure 1.

Kidney biopsy with lupus podocytopathy. (A) Light microscopy shows normal glomeruli. Immunofluorescence microscopy, not shown, is without deposits (negative for IgG, IgA, IgM, C3, and C1q). Original magnification. (B) Electron microscopy reveals complete foot process effacement (sample from paraffin with artifact). Original magnification. Courtesy of Teresa Pereda (Department of Pathology of Hospital Costa del Sol Marbella).

Figure 2.

Pathogenesis of lupus podocytopathy. (A) In lupus podocytopathy, the foot process effacement may be explained by a direct injury associated with T cell dysfunction, cytokines, or lymphokines that damage the podocyte, although pathogenesis of lupus podocytopathy is not well understood. (B) In other classes of lupus nephritis, proliferation and hypercellularity, with the infiltration of inflammatory cells and ensuing subendothelial or subepithelial deposits, indicate other mechanisms of injury related to autoantibodies and immune complex depositions. Adapted and modified from Yu et al.