Kidney Week

Abstract: FR-PO0770

Severe PR3-Dominant Hydralazine-Induced Vasculitis Presenting with C3-Dominant Glomerulonephritis

Session Information

• Glomerular Diseases: ANCA Vasculitis, Anti-GBM Disease, and Crescentic GN
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Capriles, Guido M., TriHealth Inc, Cincinnati, Ohio, United States

Guido M. Capriles, MD

• Abdeltawwab, Mohannad, TriHealth Inc, Cincinnati, Ohio, United States

Mohannad Abdeltawwab, MD, MBChB

• Rajput, Amit K., TriHealth Inc, Cincinnati, Ohio, United States

Amit K. Rajput, MD, MBA

Introduction

Hydralazine-induced ANCA-associated vasculitis (HIAV) classically presents with high-titer myeloperoxidase (MPO) antibodies and pauci-immune glomerulonephritis (GN). We present a rare, discordant phenotype of HIAV featuring massive proteinase 3 (PR3) elevation and C3-dominant immune complex deposition, mimicking primary Granulomatosis with Polyangiitis (GPA) and Lupus Nephritis. Recognizing this atypical overlap is critical to ensure prompt drug cessation.

Case Description

A 70-year-old male on chronic hydralazine therapy presented with oligoanuria and hypoxic respiratory failure. Laboratories revealed fulminant acute kidney injury (creatinine 13.8 mg/dL, baseline 0.9 mg/dL) and nephritic sediment. Serologic evaluation revealed a highly discordant profile: p-ANCA positive (1:1280) with massive PR3 elevation (1,153 AI) and low-positive MPO (30 AI). Concurrently, he exhibited strong drug-induced lupus markers: positive ANA (1:1280), anti-dsDNA, and anti-histone antibodies (4.1 U; reference <0.9). Renal biopsy demonstrated severe necrotizing crescentic GN with cellular crescents in 9 of 11 glomeruli. Immunofluorescence deviated from typical pauci-immune patterns, revealing C3-dominant (3+) granular mesangial staining with IgG (1+). Hydralazine was permanently discontinued. Given the presence of >80% crescents and dialysis-dependency, induction therapy was initiated with pulse methylprednisolone, rituximab (375 mg/m² x 2), and cyclophosphamide (500 mg IV). Despite aggressive immunosuppression, the patient remains hemodialysis-dependent at one-month follow-up.

Discussion

Distinguishing HIAV from primary GPA is paramount, as HIAV requires offending drug withdrawal for disease resolution. This case challenges traditional diagnostic heuristics. While massive PR3 dominance usually suggests primary GPA, the p-ANCA pattern and high-titer anti-histone antibodies—highly specific for drug-induced etiologies—confirmed hydralazine toxicity. Furthermore, the biopsy challenged the "pauci-immune" dogma of AAV. The C3-dominant deposition reflects an immune-complex mediated pathophysiology unique to HIAV, histologically mimicking Lupus Nephritis. This case emphasizes that PR3 positivity does not exclude a drug-induced etiology. In atypical AAV with immune deposits or discordant serologies, clinicians must evaluate for hydralazine toxicity to prevent disease relapse.