Unveiling the Enigma: Primary Membranous Nephropathy with Crescent Formation, a Puzzling Rarity

Introduction: Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. Development of crescents in MN is extremely rare (<1%) & is usually associated with a rapidly progressive course to renal failure. We report a case of crescents in primary MN, characterized by positive anti-phospholipase A2 receptor (PLA2R) antibodies with a negative ANCA profile & anti-GBM assay. Case Description: A 38-year-old male with essential hypertension presented in 2018 with anasarca & hypertensive emergency. Labs showed creatinine (Cr) of 1.1 mg/dl, hypoalbuminemia (serum albumin of 1.4 g/dl), & massive proteinuria (37.13 g/24 hrs). Serum ANCA, ANA, anti-dsDNA, & anti-GBM were negative. Anti-PLA2R was highly positive (280.3 RU/ml). A kidney biopsy with immunofluorescence (IF) & electron microscopy (EM) were consistent with Primary MN (stage 3). IF showed diffuse granular deposits of IgG, C3 & C1q. EM showed subepithelial immune deposits with extensive foot process effacement. No endocapillary proliferation, fibrinoid necrosis, or crescent were seen. Received immunosuppressant (IS) therapy per Dutch protocol, achieving partial remission. In the next 4 years, there were multiple admissions with AKI (Cr ranging between 1.9-3.5 mg/dl), as well as a COVID-19 infection in 2020. A repeat renal biopsy was performed during subsequent readmission with a Cr of 10.6 mg/dl in 2022, which revealed MN with focal crescents (7 cellular/fibro cellular & one fibrous), global sclerosis of 46%, tubular atrophy, & chronic interstitial inflammation. Anti-PLA2R was lower but still elevated (45 RU/ml). No meaningful recovery despite IS therapy, and he progressed to End-Stage Kidney Disease & started on dialysis. Discussion: The presence of crescents raised suspicion of secondary MN due to infections, neoplasms, etc. However, the lack of secondary MN indicators, negative ANA, anti-dsDNA, ANCA, anti-GBM antibodies, & highly positive anti-PLA2R ab confirmed the diagnosis. Primary idiopathic crescentic MN is rare, with crescent formation likely due to PLA2R immune complex deposition, suggesting MN progression. Although rare, the crescents could also be linked to COVID-19 infection, with no documented cases. Another possibility is the coincidental occurrence of two separate diseases. Recognizing crescents in primary MN is crucial for early & accurate management to prevent progression.