Familial Mediterranean Fever Associated with Anti-PLA2R-Positive Membranous Nephropathy: A Case-Based Review

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disease in which renal involvement is a major determinant of prognosis and is classically dominated by amyloid A (AA) amyloidosis. Non-amyloid renal manifestations are uncommon and poorly characterized. We report a case of clinically overt FMF associated with anti-phospholipase A2 receptor (PLA2R) antibody-positive membranous nephropathy (MN). A 46-year-old man with recurrent febrile episodes fulfilling Tel Hashomer criteria for FMF developed progressive proteinuria with detectable anti-PLA2R antibodies. Genetic testing identified a heterozygous missense MEFV variant in exon 10 (p.Lys695Arg), a mutation with variable penetrance and conflicting pathogenic classification. Kidney biopsy demonstrated PLA2R-positive MN, excluding amyloidosis. After initial conservative management, the patient progressed to nephrotic syndrome complicated by renal vein thrombosis, requiring immunosuppressive therapy according to the Ponticelli regimen in addition to colchicine and anticoagulation, resulting in clinical and immunological remission. In parallel, we performed a systematic review of the literature, identifying only isolated reports of biopsy-proven MN in FMF patients. This case highlights the diagnostic importance of kidney biopsy in FMF patients with proteinuria and illustrates that immune-mediated glomerular disease may occur even in association with non-founder or variably penetrant MEFV mutations, requiring disease-specific management beyond standard autoinflammatory control.