Kidney Week

Abstract: SA-PO0769

Hydralazine-Associated ANCA/Lupus-Like Overlap Nephritis: Equivocal Serology, Defining Pathology

Session Information

• Glomerular Diseases: Lupus Nephritis, Monoclonal Gammopathy-Related Disease, and Transplantation
  October 24, 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

• Luong, Paul, Meharry Medical College, Nashville, Tennessee, United States

Paul Luong, MD

• Steitz, Alyssa Davis, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Alyssa Davis Steitz, MD, MEd

• Bhave, Gautam B., Vanderbilt University Medical Center, Nashville, Tennessee, United States

Gautam B. Bhave, MD, PhD

• Paueksakon, Paisit, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Paisit Paueksakon, MD

• Bock, Fabian, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Fabian Bock, MD, PhD

Introduction

Hydralazine-associated ANCA glomerulonephritis is increasingly recognized as an overlap syndrome with drug-induced lupus-like features. Larger series show ANA, anti-histone antibodies, hypocomplementemia, anti-dsDNA, and immune-complex deposits in many cases. This case highlights a diagnostic pitfall: severe pulmonary-renal disease may have defining overlap pathology despite incomplete lupus serologies.

Case Description

A 59-year-old man with hypertension, type 2 diabetes, CKD4, and coronary artery disease taking hydralazine 75 mg/day for at least 4 years presented with dyspnea, hemoptysis, severe anemia, and progressive kidney dysfunction. Creatinine was 3.46 mg/dL from baseline ~2.0, with nephrotic-range proteinuria, microscopic hematuria, low C3/C4, positive anti-histone antibody, and initially negative ANCA IF screen. Repeat testing showed p-ANCA 1:80 with MPO antibody >8.0 and negative PR3. ANA, anti-dsDNA, anti-GBM, PLA2R, viral serologies, and paraprotein evaluation were negative. CT chest showed right lung ground glass opacities and bronchoscopy confirmed diffuse alveolar hemorrhage. Hydralazine was stopped, and high-dose steroids improved hemoptysis and stabilized kidney function. Kidney biopsy showed predominantly mesangiopathic immune-complex GN with necrotizing crescentic GN, supporting hydralazine-associated ANCA/lupus-like overlap nephritis. He received cyclophosphamide induction and was transitioned to rituximab.

Discussion

Hydralazine-associated ANCA-GN is more than a drug-induced mimic of primary ANCA vasculitis. The largest biopsy series showed that many cases carry a lupus-like signature, with ANA, anti-histone antibodies, hypocomplementemia, and immune-complex deposits accompanying necrotizing crescentic GN. Our case adds a practical caution: overlap may be pathologically present even when serologies are incomplete. This patient had severe pulmonary-renal syndrome despite an initially negative ANCA screen. Repeat testing revealed MPO-ANCA positivity, while low complement and anti-histone positivity suggested drug-induced autoimmunity. However, negative ANA and anti-dsDNA made classic drug-induced lupus nephritis less convincing. Kidney biopsy resolved the ambiguity by demonstrating both necrotizing crescentic GN and mesangiopathic immune-complex GN, guiding hydralazine withdrawal and immunosuppression.