A Novel Therapeutic Approach to ANCA-Negative Crescentic IgA Nephropathy

Introduction: IgA nephropathy is an autoimmune disorder caused by dysregulation of mucosal IgA immunoglobulins that results in deposition within the renal mesangium with variable presentations. Rarely, IgA nephropathy may lead to rapidly progressive glomerulonephritis(RPGN), characterized by gross hematuria, edema, hypertension, and acute kidney injury. Case Description: A 48 year old male with a past medical history of hypertension and type 2 diabetes mellitus presented with two days of painless, gross hematuria. Initial labs showed creatinine(Cr) 2.5mg/dl, eGFR 31ml/min, INR 1.3, platelets 253, and a urinalysis significant for moderate blood, >100 urine RBCs, and urine protein to creatinine ratio(UPCR) of 6.7. During hospitalization, the patient’s Cr peaked at 3.0, ASO >2,100, negative ANCA, and Kappa/Lambda ratio of 2.01. Kidney biopsy revealed IgA nephropathy with focal crescents. The Oxford classification score was M0 E1 S0 T1 C2. In the hospital, the patient was treated with 1g IV methylprednisolone for 3 days, followed by oral prednisone for 1 week and losartan upon discharge. On follow-up, the patient was transitioned to empagliflozin, budesonide, and sparsentan with improvement of Cr to 1.9mg/dl and UPCR of 0.5. Discussion: IgA nephropathy may lead to RPGN with poor prognosis and a 5-year progression to renal failure of 70%. The case presented as an IgA nephropathy with RPGN and negative ANCA titers. While standard treatment includes steroids and cyclophosphamide or mycophenolate mofetil, the prognosis remains poor. There is sparse research on alternative modalities. We desribe a positive outcome with the triad of novel therapies of sparsentan, budesonide and empagliflozin.Cellular crescents and necrosisIgA