What causes high creatinine levels?

Common Causes of Elevated Creatinine Levels

Elevated serum creatinine is most commonly caused by decreased kidney function, but can also result from medications, high protein intake, muscle damage, or laboratory interference. 1

Primary Causes of High Creatinine

Kidney-Related Causes

• Chronic Kidney Disease (CKD)

  • Diagnosed by persistent elevation of creatinine for >3 months 1
  • Occurs in 20-40% of patients with diabetes 2
  • Typically develops after 10 years in type 1 diabetes but may be present at diagnosis of type 2 diabetes 2

• Acute Kidney Injury (AKI)

  • Diagnosed by ≥50% sustained increase in serum creatinine over a short period 2
  • Classified into stages based on creatinine elevation:
    • Stage 1: increase ≥0.3 mg/dL up to 2-fold of baseline
    • Stage 2: increase between 2-fold and 3-fold of baseline
    • Stage 3: increase >3-fold or creatinine >4 mg/dL with acute increase 1

Medication-Related Causes

• Nephrotoxic medications:

  • NSAIDs
  • Aminoglycosides
  • Contrast media
  • Certain chemotherapeutic agents
  • Immune checkpoint inhibitors (causing interstitial nephritis in 2-5% of patients) 1

• Medications affecting creatinine secretion:

  • Trimethoprim and pyrimethamine can reduce renal secretion of creatinine 1
  • ACE inhibitors or ARBs may cause temporary creatinine increases up to 30% 2

Other Common Causes

• High protein intake or creatine supplementation 1, 3

  • Creatine-containing dietary supplements can artificially elevate serum creatinine 3

• Increased muscle breakdown

  • Rhabdomyolysis
  • Extreme exercise
  • Trauma or burns

• Dehydration or volume depletion 2

  • Often occurs with diuretic use 2

Risk Factors for Elevated Creatinine

• Age: Older adults have higher prevalence of elevated creatinine 4
• Sex: Men have higher baseline creatinine levels than women 4, 5
• Hypertension: Treatment for hypertension is associated with elevated creatinine (OR 1.75 in men, 1.42 in women) 4
• Diabetes: Especially when combined with hypertension treatment (OR 2.94) 4
• Body mass index: Higher BMI correlates with higher creatinine in men 4
• Cardiovascular disease: Use of cardiac medications increases risk (OR 1.58 in women) 4

Clinical Significance

• Elevated serum creatinine is a potent independent risk factor for mortality 6
• Levels above 116 μmol/L (1.3 mg/dL) are associated with increased stroke risk 7
• Levels ≥1.7 mg/dL are associated with more than three times higher 8-year mortality 6

Important Considerations

• Do not discontinue ACE inhibitors/ARBs for minor increases in serum creatinine (≤30%) in the absence of volume depletion 2, 1
• Avoid labeling patients with CKD based on a single elevated creatinine measurement; confirm persistence over at least 3 months 1
• Consider cystatin C as an alternative marker when creatinine may be less accurate (affected by muscle mass, diet, etc.) 1, 5
• Monitor both eGFR and albuminuria to properly assess kidney function 1

When to Refer to Nephrology

• eGFR <30 mL/min/1.73 m² 2
• Rapid decline in kidney function (>5 mL/min/1.73m²/year) 1
• Significant albuminuria (UACR >300 mg/g) 1
• Uncertainty about etiology of kidney disease 2
• Difficult management issues 2

Remember that serum creatinine is influenced by factors such as muscle mass, age, gender, and diet, making it an imperfect marker of kidney function when used alone 5.