Not-So-Pauci-Immune Crescentic Glomerulonephritis: A Management Challenge with Poor Kidney Survival

Introduction: Glomerulonephritis (GN) caused by antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV) classically presents on renal biopsy as a pauci-immune GN. However, glomerular immune complex deposition is becoming increasingly recognized as a potential pathologic presentation. Studies have reported significant immune complex deposition (26%-41%) in patients diagnosed with AAV. Reported immune deposits on direct immunofluorescence (DIF) have included IgG, IgM, IgA, C3, C4, and C1q in varying combinations. Higher degrees of proteinuria and worse renal outcomes have been associated with reported immune complexes on DIF in AAV patients, particularly with myeloperoxidase (MPO) positivity. Low serum C3 and glomerular IgG deposits are also indicators of poor renal prognosis. Case Description: We present a patient, previously healthy, who was hospitalized with hypertensive emergency, mixed nephritic and nephrotic syndrome, and acute renal failure requiring initiation of hemodialysis. Labs were notable for MPO positivity with normal C3 and C4. All other serologies were negative.The patient was initiated on empiric induction with intravenous cyclophosphamide and methylprednisolone. Renal biopsy revealed a crescentic GN and DIF positivity for IgG, C3, C1q, kappa, and lambda. Despite induction therapy for over three months duration, the patient remained dialysis dependent with continued positive MPO serologies. Rheumatology evaluation revealed no evidence of extrarenal disease. He was transitioned to mycophenolate mofetil maintenance therapy and is undergoing evaluation for renal transplantation. Discussion: This case exemplifies the severe nature and therapeutic challenge posed by ANCA-associated RPGN with immune complex deposition and may indicate that current standard therapies may not be adequate for this pathologic variant. Further research is needed to elucidate effective immunosuppressive therapy for these patients.