Atypical Antiglomerular Basement Membrane Disease in a Pediatric Patient Successfully Treated with Rituximab

Abstract

Classic antiglomerular basement membrane (anti-GBM) disease is an exceedingly rare but extremely aggressive form of glomerulonephritis, typically caused by autoantibodies directed against cryptic, conformational epitopes within the noncollagenous domain of the type IV collagen alpha-3 subunit. Pathologic diagnosis is established by the presence of strong, diffuse, linear staining for immunoglobulin on immunofluorescence microscopy. Recently, patients with atypical clinical and pathologic findings of anti-GBM disease have been described. These patients tend to have an indolent clinical course, without pulmonary involvement, and laboratory testing rarely reveals the presence of anti-GBM antibodies. Specific guidelines for the treatment and management of these patients are unclear. Here, we describe a case of atypical anti-GBM disease in a young child who presented with hematuria and prominent proteinuria. Throughout the course of his illness, creatinine remained normal. He was conservatively treated with steroids and rituximab, resulting in resolution of his clinical symptoms and normalization of laboratory findings.

Figure 1

Renal biopsy findings. (a) One glomerulus showing segmental endocapillary hypercellularity, karyorrhectic nuclear debris, and a small cellular crescent (periodic acid-Schiff; original magnification: 400x). (b) Nearly, all of the remaining glomeruli demonstrate no significant abnormalities (periodic acid-Schiff; original magnification: 200x). (c) Immunofluorescence for IgG reveals diffuse, global, linear staining within the glomerular basement membrane (original magnification: 200x). (d) Widespread, subtle subendothelial widening is noted on electron microscopy, without the presence of any immune deposits (original magnification: 4800x).

Figure 2

Degree of proteinuria and antiglomerular basement membrane (anti-GBM) antibody levels during the course of illness. Spot urine protein-to-creatinine ratio (solid line) and anti-GBM antibody levels (dotted line) are shown relative to the time of biopsy. ^∗Limit of detection for anti-GBM antibody levels is 1.0 AI, which has remained <1.0 AI since day 43. ^∗∗Limit of detection for urine protein-to-creatinine ratio is 0.19, which has remained between <0.19 and 0.25 since day 64. Data extend to day 334 at the latest follow-up. Length of treatment is indicated by black bars below the X-axis.