Positive Antiphospholipase A2 Receptor in Membranoproliferative Glomerulonephritis (MPGN): What to Do?

Introduction: This case highlights the diagnostic and therapeutic challenges of nephrotic syndrome and chronic kidney disease. Initially diagnosed as MPGN post-myocardial infarction, secondary causes were excluded. Despite immunosuppressive therapy, treatment resistance persists, and a positive PLA2R test necessitates further investigation. Case Description: A 46-year-old patient with a history of nephrotic syndrome (proteinuria 9.36 g/day) underwent a left kidney biopsy in September 2021, revealing MPGN with IgG and IgM deposits and GBM duplication. Secondary causes were excluded, with negative hepatitis markers, normal immune function, and unremarkable serum and urine immunoelectrophoresis. The renal disease was first identified after an acute inferior myocardial infarction in February 2021. Comorbidities include hypertensive heart disease with severe left ventricular hypertrophy and ischemic heart disease. The patient initially received a single course of corticosteroids, discontinued upon request. By June 2024, now 49 Y.O., the patient was admitted for glomerular disease activity with nephrotic-range proteinuria (>5 g/24h) and advanced chronic kidney disease (serum creatinine 301 μmol/L, MDRD eGFR 20 mL/min). Extensive evaluation ruled out chronic infections (CMV, EBV), malignancy (tumor markers), immune disorders, Fabry disease, and T-SPOT TB, with the sole positive test being PLA2R antibody (1:1000, normal 1:10). Ultrasound revealed enlarged kidneys, high parenchymal echogenicity, and nephrocalcinosis. The patient underwent six months of immunosuppressive therapy with corticosteroids and cyclophosphamide (cumulative dose 3000 mg) but remained resistant to treatment. Management focused on symptomatic therapy, including diuretics, anticoagulants, dapagliflozin, and antihypertensive medications. Discussion: The presented clinical case raises two key points for discussion—one concerning diagnosis and the other therapy. Regarding the diagnosis, there is a notable discrepancy between the histological findings from the kidney biopsy and the laboratory diagnostics. As for the therapy, the condition appears to be treatment-resistant chronic glomerulonephritis. What comes next? Is this a form of primary glomerular kidney disease, or could it represent a distinct pathological entity? A second kidney biopsy, complemented by electron microscopy, is planned to provide a definitive answer.