Concurrent IgG4-related membranous nephropathy and proliferative diabetic kidney disease: a diagnostic dilemma and therapeutic strategy in long-standing diabetes

Abstract

Background: IgG4-related kidney disease (IgG4-RKD) overlapping with diabetic nephropathy (DND) poses diagnostic challenges in terms of histopathological mimicry. This report highlights the first case of concurrent IgG4-related membranous nephropathy (IgG4-MN) and proliferative diabetic kidney disease (DKD) in a patient with diabetes, emphasizing the use of multidisciplinary diagnostic approaches. A 74-year-old male with a 24-year history of diabetes presented with nephrotic syndrome (proteinuria: 6.9 g/24 h), hypoalbuminemia (26.6 g/L), and lymphadenopathy. The patient’s serum IgG4 levels were markedly elevated (2774.7 mg/L). Renal biopsy revealed IgG4-dominant subepithelial deposits (PLA2R-negative) with diabetic glomerulosclerosis, whereas lymph node histopathology confirmed the diagnosis of IgG4-related disease (IgG4-RD). Despite the absence of classic IgG4 + tubulointerstitial nephritis (TIN), integrative serological (hypergammaglobulinemia, IgE elevation), radiological (lymphadenopathy), and histological evidence confirmed the diagnosis of IgG4-MN. Low-dose prednisone and mycophenolate mofetil achieved partial remission (50% proteinuria reduction) without compromising glycemic control. Conclusion: This case highlights the diagnostic complexity of dual renal pathologies in individuals with diabetes and underscores the necessity of multidisciplinary evaluation to differentiate IgG4-MN from DND or primary membranous nephropathy. Early recognition of IgG4-RKD in patients with diabetes and disproportionate proteinuria or systemic inflammation is critical to guide targeted immunosuppression while mitigating metabolic risk. The favorable outcome in this case emphasizes the efficacy of tailored, low-intensity regimens in comorbid populations.