Medication-Induced Changes in Serum Creatinine

Introduction to Medication-Induced Changes

• Medications can cause changes in serum creatinine levels, which may not always reflect actual kidney function, as noted by the American College of Clinical Pharmacology, National Kidney Foundation, and European Renal Association 1

Medications Causing False Elevations in Serum Creatinine

• Trimethoprim-containing medications, such as trimethoprim/sulfamethoxazole, can cause elevations in serum creatinine without reducing kidney function, as they competitively inhibit tubular secretion of creatinine, according to the American College of Clinical Pharmacology 1
• Cimetidine and pyrimethamine can also inhibit tubular secretion of creatinine, leading to increased serum creatinine levels, as noted by the National Kidney Foundation 1
• Angiotensin receptor neprilysin inhibitors (ARNIs) can cause an expected 10-15% increase in creatinine within the first 2 weeks, with up to 25% increase in patients with renal insufficiency, as stated by the European Renal Association 1

Medications Causing True Renal Impairment

• Nephrotoxic antimicrobials, such as amphotericin B, cidofovir, and foscarnet, can cause renal effects in up to 80% of patients, including hypokalemia, renal tubular acidosis, and elevated creatinine, as recommended by the Infectious Diseases Society of America 1
• Bisphosphonates (IV) can cause renal impairment, especially with rapid infusion, and require monitoring of serum creatinine, according to the American Society of Clinical Oncology 2
• Immune checkpoint inhibitors can cause immune-related nephritis, with grade 2 nephritis characterized by creatinine 2-3× above baseline, and grade 3-4 characterized by creatinine ≥3× above baseline or ≥4.0 mg/dL, as stated by the European Society for Medical Oncology 3
• Deferasirox (iron chelator) can cause mild elevations in serum creatinine in ~33% of patients and is contraindicated if creatinine clearance <40 mL/min, as recommended by the American Heart Association 4
• ACE inhibitors and ARBs can cause a predictable increase in serum creatinine (up to 20% considered acceptable), due to altered intraglomerular hemodynamics, as noted by the British Journal of Pharmacology 5
• Tenofovir requires renal monitoring before and during treatment, as it can cause renal impairment in HIV patients, as recommended by the Clinical Infectious Diseases journal 6

Management of Medication-Induced Changes in Serum Creatinine

• Baseline creatinine should be established before starting therapy with nephrotoxic drugs, and creatinine should be monitored regularly during treatment, with adequate hydration, especially with amphotericin B, cidofovir, and foscarnet, as recommended by the National Kidney Foundation 1
• For ACE inhibitors/ARBs/ARNIs, an expected 10-25% increase in creatinine is acceptable, but medication should be held if creatinine increases ≥30% from baseline, as stated by the American College of Clinical Pharmacology 5
• Drug interactions should be considered, and medication doses adjusted in renal impairment, as many medications require dose adjustments based on creatinine clearance, according to the European Renal Association 1
• ARNI therapy should not be discontinued for minor increases in serum creatinine (<30%) in the absence of volume depletion, as recommended by the American Diabetes Association 7
• Small elevations in serum creatinine with RAS blockers should not be confused with acute kidney injury, as stated by the American Diabetes Association 7
• Patients on ARNI therapy should have their potassium levels monitored closely, especially in patients with eGFR <60 mL/min/1.73m², according to the American Diabetes Association 7
• Patients with normal renal function can expect a ~10% increase in serum creatinine, while patients with renal insufficiency can expect up to 25% increase in serum creatinine, as reported by the American Diabetes Association 7
• Most increases in serum creatinine occur within the first 2 weeks (~15%) with more gradual increases (~10%) in weeks 3-4, as reported by the American Diabetes Association 7
• ARNI therapy should be held when serum creatinine increases by ≥30% from baseline within the first 2 months of therapy, and should be discontinued permanently if serum creatinine rises by ≥50% from baseline or reaches ≥4.0 mg/dL
• The development of hyperkalemia (serum potassium ≥5.6 mmol/L) or the need for renal replacement therapy are also indications for discontinuing ARNI therapy