Membranous Nephropathy as a Manifestation of IgG4‐Related Disease (IgG4‐RD): A Case Report

Abstract

IgG4-related disease (IgG4-RD) is an immune-mediated, inflammatory condition that can affect multiple organs, marked by lymphoplasmocytic infiltration and IgG4-positive plasma cells. Elevated serum IgG4 is common but not essential. Sole renal manifestation is rare, usually appearing as tubulointerstitial nephritis (TIN) or, less commonly, membranous nephropathy (MN).

We present a case of an 87-year-old man with a medical history of hypertension, dyslipidemia, ischemic cardiomyopathy, and COPD. The patient presented with nephrotic syndrome (proteinuria/creatininuria ratio (P/C ratio) of 11g/g) and acute kidney injury (creatinine 4mg/dl). Urinalysis indicated proteinuria and haematuria without dysmorphic erythrocytes. Investigation revealed normochromic normocytic anaemia, hypoalbuminemia, and no evidence of monoclonal gammopathy or hypocomplementemia. Serologies for HIV, hepatitis B, and hepatitis C were negative. Antinuclear, anti-neutrophil, and anti-phospholipase A2 antibodies (anti-PLA2r) were also negative. Treatment including anti-proteinuric and anticoagulation therapies was initiated. Kidney biopsy displayed membranous nephropathy and interstitial nephritis; immunofluorescence showed parietal granular deposits of IgG-κ and IgG-λ; immunohistochemistry revealed lymphocytes, plasma cells (with more than 10 IgG4-positive cells per high-power field), and IgG4 deposits on the glomerular basement membrane. Serum IgG subclass levels detected a slight elevation of IgG4. Other organ involvements hinting at IgG4-RD were ruled out. Assuming IgG4-RD with renal involvement therapy with prednisolone (40mg/day) was started and after one month the patient demonstrated a significant improvement in kidney function, anaemia, hypoalbuminemia, and proteinuria.

Although renal manifestation as the first and/or only manifestation of IgG4-RD is rare, should be suspected in renal cases showing MN with or without TIN, especially when anti-PLA2R is negative.