Does Hydralazine Cause Kidney Failure?
Hydralazine does not directly cause kidney failure in most patients; in fact, it typically increases renal blood flow and maintains glomerular filtration rate in hypertensive patients with normal kidneys. 1, 2 However, hydralazine can rarely cause severe acute kidney injury through drug-induced ANCA-associated vasculitis, and the drug accumulates in patients with pre-existing chronic kidney disease, requiring dose adjustment. 1, 3, 4
Direct Renal Effects in Normal Kidney Function
In hypertensive patients with normal kidneys, hydralazine increases renal blood flow and maintains glomerular filtration rate, and in some cases where baseline renal function was below normal, improved renal function has been noted after hydralazine administration. 2
Hydralazine acts as a potent vasodilator through increased nitric oxide availability, which lowers blood pressure and potentially increases renal arterial flow, particularly demonstrated during intravenous administration in acute settings. 1
The combination of hydralazine with isosorbide dinitrate has been shown to decrease mortality in patients with pre-existing renal failure, suggesting it can be safely used in this population when appropriately monitored. 1
Rare but Serious: Drug-Induced ANCA Vasculitis
Hydralazine can rarely cause drug-induced ANCA-associated vasculitis leading to crescentic (pauci-immune) glomerulonephritis, which presents with severe acute kidney injury, proteinuria, and hematuria. 3, 5
This complication typically presents with positive ANCA serology along with anti-histone antibodies (commonly seen in drug-induced vasculitis), and renal biopsy reveals classic crescentic glomerulonephritis. 3, 5
Case reports document patients developing severe AKI with serum creatinine rising from baseline 0.9 mg/dL to levels requiring dialysis, with some patients progressing to advanced chronic kidney disease (stage IIIb) or death despite treatment with steroids, rituximab, and plasmapheresis. 3
The risk of hydralazine-induced lupus (which can involve the kidneys leading to renal dysfunction) increases with prolonged use, making this a critical consideration for long-term therapy. 1
Drug Accumulation in Pre-Existing Kidney Disease
Hydralazine is renally excreted and accumulates in patients with chronic kidney disease, particularly when GFR falls below 30 mL/min. 1, 4
The serum half-life of hydralazine increases dramatically as GFR decreases: from 1.7-3.0 hours in healthy volunteers to 15.8 hours in a patient with GFR of 16 mL/min. 4
The ratio between minimum steady-state drug concentration and daily dose increases as GFR decreases, with particularly evident accumulation in patients with GFR less than 30 mL/min. 4
Despite this accumulation, the FDA label states that hydralazine should be used with caution (not avoided) in patients with advanced renal damage, as the drug can still provide benefit when appropriately dosed. 2
Clinical Monitoring Requirements
Complete blood counts and antinuclear antibody titer determinations are indicated before and periodically during prolonged therapy with hydralazine, even in asymptomatic patients. 2
These studies are particularly indicated if the patient develops arthralgia, fever, chest pain, continued malaise, or other unexplained signs or symptoms that could herald drug-induced lupus or vasculitis. 2
Blood dyscrasias (reduction in hemoglobin and red cell count, leukopenia, agranulocytosis, and purpura) have been reported, and if such abnormalities develop, therapy should be discontinued. 2
Use in Heart Failure with Renal Insufficiency
The 2022 AHA/ACC/HFSA guidelines state that hydralazine-isosorbide dinitrate might be considered as a therapeutic option in patients who are intolerant of ACE inhibitors or ARBs due to renal insufficiency, though the potential benefit is unknown. 1
This recommendation is based on the V-HeFT I trial showing mortality reduction with hydralazine-isosorbide dinitrate in heart failure patients, though this was before widespread ACE inhibitor use. 1
For African Americans with HFrEF who remain symptomatic despite optimal therapy with ACE inhibitors, beta blockers, and mineralocorticoid receptor antagonists, the addition of hydralazine-isosorbide dinitrate is recommended to reduce morbidity and mortality. 1
Common Pitfalls to Avoid
Do not confuse hydralazine's renal accumulation (requiring dose adjustment) with direct nephrotoxicity—the drug itself does not damage kidneys through toxic mechanisms in the vast majority of patients. 1, 2, 4
Do not overlook early signs of drug-induced lupus or ANCA vasculitis (arthralgia, fever, unexplained malaise, new proteinuria/hematuria), as prompt discontinuation and immunosuppressive therapy may prevent progression to dialysis-dependent kidney failure. 2, 3, 5
Avoid using hydralazine without monitoring in patients with GFR <30 mL/min, as significant drug accumulation occurs and dose reduction is necessary. 4
Do not assume that worsening renal function in a patient on hydralazine is due to the drug without first evaluating for volume depletion, hypotension, or concomitant nephrotoxic medications. 1