Overlapping IgM Mesangioproliferative Glomerulonephritis (GN) and ANCA-Associated Crescentic GN Associated with Hydralazine

Introduction: Hydralazine, a commonly used antihypertensive agent, has been associated with the development of anti-neutrophilic cytoplasmic antibody-glomerulonephritis (ANCA-GN) in susceptible individuals. Hydralazine-induced ANCA-GN can mimic primary ANCA-GN with necrotizing and crescentic glomerulonephritis. However, distinct pathological differences have been observed. Compared to primary ANCA-GN, hydralazine-associated cases exhibit a higher frequency of mesangial hypercellularity (30% vs 5%) and a lower incidence of pauci-immune features (77 vs 100%).1 Case Description: Patient is an 85-year-old woman with a history of asthma, hypertension, hyperlipidemia, and pulmonary hypertension who was evaluated for elevated creatinine in the 3 to 4 range and reduced glomerular filtration rate of 11 mL/min/1.73m2. She reported generalized fatigue, unintentional ninety-pound weight loss, and intermittent nausea and diarrhea. She had no prior history of acute kidney injury, kidney stones, NSAID use, contrast exposure, or new medications. Initial work up consisted of serum creatinine 4.42 mg/dL, eGFR 9 mL/min/1.73m2, hemoglobin 7 g/dL, sub nephrotic range proteinuria, large blood with 80-100 rbc/hpf, antinuclear antibody titer 1:1280, p-ANCA titer 1:640, and myeloperoxidase antibody greater than 8 units. Renal ultrasound showed 2 simple cysts on the right kidney but was otherwise unremarkable. Kidney biopsy showed IgM dominant mesangioproliferative glomerulonephritis with rare crescents. She was diagnosed with hydralazine induced ANCA vasculitis overlapping with IgM immune complex glomerulonephritis with crescent formation. Hydralazine was discontinued, and she was started on rituximab infusions and high dose steroids. She responded well to treatment with her creatinine and eGFR improving to 2.6 mg/dl and 19 ml/min/1.73m2. Discussion: This case is notable for the presence of perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA), myeloperoxidase (MPO) antibodies, and IgM mesangioproliferative glomerulonephritis with rare crescent formation. Given the widespread use of hydralazine, hydralazine-induced glomerulonephritis (GN) should remain a consideration in the differential diagnosis. Management typically involves immunosuppressive therapy and discontinuation of hydralazine, with clinical outcomes comparable to those observed in primary ANCA-associated GN.