What medications can cause impaired renal function?

Medications That Cause Kidney Damage

Numerous medications can cause kidney damage through direct tubular toxicity, hemodynamic effects, allergic reactions, or crystal deposition, with NSAIDs, aminoglycosides, ACE inhibitors/ARBs, and certain chemotherapy agents being the most clinically significant nephrotoxins.

Classification by Mechanism

The KDIGO guidelines provide a useful framework for understanding drug-induced kidney injury by distinguishing between dysfunction (hemodynamic changes) and injury (structural damage) 1:

Drugs Causing Both Dysfunction AND Injury

• NSAIDs (ibuprofen, naproxen, indomethacin, aspirin, sulindac) - cause both hemodynamic effects and direct tubular damage 1
• These are particularly dangerous because they combine reduced renal perfusion with structural injury 1

Drugs Causing Dysfunction Without Injury (Hemodynamic Effects)

• ACE inhibitors and ARBs - reduce intraglomerular pressure, particularly dangerous in volume-depleted or elderly patients 1
• Alpha-1 adrenergic blockers (prazosin) - worsen renal sodium retention 1
• Angiotensin II antagonists - similar mechanism to ACE inhibitors 1

Drugs Causing Injury Without Dysfunction (Direct Toxicity)

• Aminoglycosides (gentamicin, amikacin) - direct tubular cell injury, accounting for approximately 10% of hospital-acquired AKI 1, 2, 3, 4
• Acyclovir - causes crystalline nephropathy through tubular obstruction 1
• VEGF antagonists - cause direct vascular injury 1

High-Risk Antibiotic Classes

Antibiotics account for approximately 60% of drug-related kidney damage in hospitalized patients 2:

• Aminoglycosides (gentamicin, amikacin) - most common antibiotic cause, with nephrotoxicity appearing 8-17 days after initiation 3, 4
• Vancomycin - causes acute tubular injury and interstitial nephritis 4
• Beta-lactams (cefazolin, ceftriaxone) - can cause AKI through allergic interstitial nephritis 4
• Amphotericin B - significant tubular toxicity 4
• Ciprofloxacin - increased CNS effects and tendon rupture risk in renal impairment 1
• Trimethoprim-sulfamethoxazole - worsens renal function and causes hyperkalemia, especially with ACE inhibitors/ARBs 1

Chemotherapy and Targeted Cancer Agents

Cytotoxic chemotherapy is a relatively common cause of both acute and chronic kidney disease 1:

Cytotoxic Agents

• Platinum compounds (especially cisplatin) - most common cause of chemotherapy-induced kidney injury 1
• Ifosfamide - causes tubular injury and Fanconi syndrome 1
• Methotrexate - crystalline nephropathy 1
• Gemcitabine and pemetrexed - acute tubular injury 1

Targeted Therapies

• Anti-angiogenesis drugs - cause hypertension, proteinuria, thrombotic microangiopathy 1
• BRAF and ALK inhibitors - acute tubular injury and interstitial nephritis 1
• Proteasome inhibitors - associated with thrombotic microangiopathy 1
• Immune checkpoint inhibitors - primarily cause acute interstitial nephritis 1

Cardiovascular Drugs Requiring Caution

Drug accumulation from reduced renal excretion is the most important cause of adverse drug reactions in patients with kidney disease 1:

• Digoxin - narrow therapeutic window, requires dose adjustment 1
• Lithium - NSAIDs increase lithium levels by 15% and reduce clearance by 20% 5
• Dofetilide - risk of QT prolongation and torsades de pointes 1

Critical Drug Interactions That Worsen Kidney Function

• NSAIDs + ACE inhibitors/ARBs - in elderly or volume-depleted patients, can cause acute renal failure 5
• NSAIDs + diuretics - reduces natriuretic effect and increases renal failure risk 5
• TMP-SMX + ACE inhibitors/ARBs - significantly increases hyperkalemia risk 1
• Aminoglycosides + other nephrotoxins - synergistic toxicity 2

High-Risk Patient Populations

Susceptibility factors that increase risk of drug-induced kidney injury include 1:

• Advanced age (particularly >45 years for aminoglycosides) 3
• Pre-existing chronic kidney disease 1, 6
• Volume depletion or dehydration (OR=3.4 for AKI) 4
• Diabetes mellitus (OR=2.6 for antibiotic-induced nephrotoxicity) 4
• Concomitant use of multiple nephrotoxic medications (OR=2.1) 4
• Female gender and Black race 1

Drugs to Absolutely Avoid in Patients with Ascites/Cirrhosis

NSAIDs should NOT be used in patients with cirrhosis and ascites due to high risk of acute renal failure, hyponatremia, and diuretic resistance 1. This includes:

• Indomethacin, ibuprofen, aspirin, sulindac 1
• ACE inhibitors and ARBs - can induce arterial hypotension and renal failure even in low doses 1
• Aminoglycosides - reserve only for infections without alternative antibiotics 1

Clinical Monitoring Approach

Monitor renal function dynamically during all phases of acute kidney disease, with reassessment as patients transition between stages 1:

• Baseline creatinine and eGFR before initiating high-risk medications 1
• Use CKD-EPI equation for most accurate eGFR estimation 1
• Daily monitoring during aminoglycoside therapy, as oliguria may not occur despite significant kidney damage 3
• Therapeutic drug monitoring when available 1
• Urinalysis for proteinuria and cylindruria 3