What medications can elevate creatinine levels?

Medications That Can Elevate Serum Creatinine Levels

Trimethoprim-containing medications are the most common drugs that cause elevations in serum creatinine without actually reducing kidney function, as they competitively inhibit tubular secretion of creatinine. 1, 2, 3

Medications That Elevate Creatinine Without Reducing Kidney Function

These medications increase serum creatinine through mechanisms that don't involve actual kidney damage:

• Trimethoprim/Sulfamethoxazole (TMP-SMX)

  • Trimethoprim competitively inhibits tubular secretion of creatinine 1, 3
  • Can increase creatinine by 0.12-2.0 mg/dL 1, 2
  • Effect is dose-dependent and reversible within 7 days after stopping 2, 3
  • Higher doses (>160 mg/day of trimethoprim) cause greater elevations 3

• Cimetidine

  • Inhibits tubular secretion of creatinine 4
  • Does not affect actual glomerular filtration rate

• Pyrimethamine

  • Inhibits tubular secretion of creatinine 4
  • Used in toxoplasmosis treatment

• Angiotensin Receptor Neprilysin Inhibitors (ARNIs)

  • Cause expected 10-15% increase in creatinine within first 2 weeks 5
  • Up to 25% increase in patients with renal insufficiency 5
  • Should not be discontinued for increases <30% 5

• Corticosteroids

  • May modify production rate and release of creatinine 4

• Salicylates

  • Can inhibit creatinine secretion at high doses 4

Medications That Cause Actual Kidney Injury

These medications can cause true renal impairment:

• Nephrotoxic Antimicrobials:

  • Amphotericin B: Causes renal effects in up to 80% of patients 6

    • Effects include hypokalemia, renal tubular acidosis, elevated creatinine
    • Lipid formulations are less nephrotoxic

  • Cidofovir: Causes dose-dependent nephrotoxicity 6

    • Contraindicated if creatinine clearance <55 mL/min
    • Requires probenecid co-administration and hydration

  • Foscarnet: Major side effect is renal toxicity 6

    • Requires hydration before and during infusion

  • Pentamidine: Known nephrotoxic potential 6

• Bisphosphonates (IV):

  • Can cause renal impairment, especially with rapid infusion 6
  • Monitoring of serum creatinine recommended 6

• Immune Checkpoint Inhibitors:

  • Can cause immune-related nephritis 6
  • Grade 2 nephritis: creatinine 2-3× above baseline
  • Grade 3-4: creatinine ≥3× above baseline or ≥4.0 mg/dL

• Deferasirox (iron chelator):

  • Causes mild elevations in serum creatinine in ~33% of patients 6
  • Contraindicated if creatinine clearance <40 mL/min 6
  • Cases of Fanconi syndrome reported 6

• NSAIDs:

  • Can cause acute kidney injury through hemodynamic effects 7
  • Risk increases with dehydration, pre-existing kidney disease, or heart failure

• ACE Inhibitors and ARBs:

  • Cause predictable increase in serum creatinine (up to 20% considered acceptable) 6
  • Effect is due to altered intraglomerular hemodynamics 6
  • Increased risk when combined with other high-risk medications 6

• Tenofovir:

  • Requires renal monitoring before and during treatment 6
  • Can cause renal impairment in HIV patients 6

Monitoring Recommendations

1. For TMP-SMX and other drugs affecting creatinine secretion:

   • Recognize that creatinine elevations may not reflect actual kidney function
   • Consider using 24-hour urine collection to estimate creatinine clearance 6
   • Monitor electrolytes as TMP can also cause hyponatremia and hyperkalemia 3

2. For nephrotoxic drugs:

   • Establish baseline creatinine before starting therapy
   • Monitor creatinine regularly during treatment
   • Ensure adequate hydration, especially with amphotericin B, cidofovir, and foscarnet 6

3. For ACE inhibitors/ARBs/ARNIs:

   • Expect 10-25% increase in creatinine 5
   • Hold medication if creatinine increases ≥30% from baseline 5
   • Discontinue permanently if creatinine rises ≥50% or reaches ≥4.0 mg/dL 5

Common Pitfalls to Avoid

• Misinterpreting TMP-induced creatinine elevation as kidney injury

  • The effect is reversible and doesn't reflect actual GFR reduction 1, 2, 3

• Prematurely discontinuing beneficial medications

  • Small increases in creatinine with ACE inhibitors/ARBs (up to 20%) are expected and acceptable 6

• Failing to consider drug interactions

  • Combinations of nephrotoxic drugs or drugs affecting creatinine secretion can have additive effects

• Not adjusting medication doses in renal impairment

  • Many medications require dose adjustments based on creatinine clearance

By understanding which medications affect creatinine levels and through which mechanisms, clinicians can make more informed decisions about continuing, adjusting, or discontinuing therapies when faced with elevated creatinine levels.