Anti-LRP2 Nephropathy With Abundant IgG4-Positive Plasma Cells: A Case Report

In older adults, the most common kidney biopsy diagnoses include pauci-immune crescentic glomerulonephritis, membranous nephropathy, and focal segmental glomerulosclerosis. Recently, investigators described a small series of older patients (aged 66-80 years) with acute kidney injury and a kidney biopsy demonstrating tubular basement membrane (TBM) immune deposits of polytypic immunoglobulin G (IgG) and C3, acute tubular injury, and tubulointerstitial inflammation. They identified a circulating antibody against kidney tubular low-density lipoprotein (LDL) receptor-related protein 2 (LRP2; also known as megalin) in patients' sera and colocalization of LRP2 with IgG in TBM deposits. We present a rare case of anti-LRP2 nephropathy/anti-brush border antibody disease and describe the novel feature of abundant IgG4-positive interstitial plasma cells. Along with the combination of TBM deposits, tubulointerstitial nephritis (TIN), and segmental glomerular subepithelial immune deposits seen in both entities, this newly described feature adds to the morphologic overlap with IgG4-related TIN. Identification of large TBM deposits using light microscopy and IgG staining of apical aspects of proximal tubules using immunofluorescence microscopy can point to the correct diagnosis of anti-LRP2 nephropathy and prompt confirmatory studies. Particularly in older patients with immune complex-mediated TIN who lack clinical, laboratory, radiographic, and/or characteristic histologic features of IgG4-TIN or other autoimmune, infectious, or drug-related injury, a diagnosis of anti-LRP2 nephropathy should be considered.