First Reported Case of Rapidly Progressive Glomerulonephritis (RPGN) Due to Combined Renal-Limited ANCA-Associated Vasculitis and Anti-glomerular Basement Membrane (GBM) Disease in a Young Man with Koolen-de Vries Syndrome

Introduction: Koolen-de Vries syndrome (KdVS) is characterized by congenital malformations, developmental and intellectual disability, hypotonia, epilepsy, and behavioral features. Other findings include speech and language delay (100%), epilepsy (~33%), congenital heart defects (25%-50%), and renal and urologic anomalies (25%-50%) that include cryptorchidism, hypospadias, hydronephrosis/VUR, and renal duplication. Concomitant glomerular disease has not been reported to date. We describe the first case of combined renal limited ANCA Vasculitis (AAV) and Anti-GBM Disease in a patient with KdVS. Case Description: A 24-year-old male with KdVS and morbid obesity presented with reduced energy levels and rapid loss of kidney function. He did not have pulmonary manifestations including hemoptysis. His baseline serum creatinine level was unknown. On presentation, Sr Cr 4 mg/dL [was 1.7 mg/dL 1 month prior], Sr albumin 4.3 g/dL, UACR 346 mg/g and UPCR 755 mg/g. Urinalysis revealed acanthocytes. Serological workup revealed ANA (+), 1:320 [homogenous], negative ds-DNA, c-ANCA >1:1280; p-ANCA 1:220; anti-MPO titer of 96, anti-PR-3 titer of 23, anti-GBM titer of 4.7. Remainder of comprehensive serological testing was negative. Kidney USG revealed mild right pelviectasis. Patient refused PLEX and kidney biopsy. Pulse dosing of methylprednisolone and one dose of intravenous cyclophosphamide 1000 mg was given followed by oral cyclophosphamide at 200 mg/day. After 8 months, UPCR 600 mg/g, no acanthocyturia; he has attained serological remission of his MPO, PR-3, and Anti-GBM serologies and has a Sr Cr stable at 2.4 mg/dL. Discussion: AAV with concomitant anti-GBM disease is a rare, potentially life-threatening disease. Prompt diagnosis with a kidney biopsy is warranted to ascertain extent of cellular activity. Early treatment with PLEX, cyclophosphamide, and glucocorticoids is warranted. Dual AAV (+) Anti-GBM mandates immunosuppression for remission maintenance as well as portend a poor prognosis. We describe the first case of RPGN due to combined renal limited AAV and Anti-GBM Disease in a patient with Koolan-De Vries Syndrome, and the associated challenges with treatments.