Can taking supplemental testosterone or creatine (Creatine Monohydrate) increase my serum creatinine levels, indicating Impaired Renal Function?

Impact of Testosterone and Creatine Supplementation on Serum Creatinine Levels

Both testosterone and creatine supplementation can increase serum creatinine levels without indicating actual kidney dysfunction or impaired renal function.

Creatine Supplementation Effects on Serum Creatinine

Mechanism and Evidence

• Creatine supplementation can cause a transitory rise in serum creatinine levels that may falsely suggest kidney dysfunction 1.
• This occurs because creatine is spontaneously converted to creatinine in the body 2.
• The elevation in serum creatinine from creatine supplementation is not associated with actual renal impairment when measured by more accurate methods of kidney function 3.

Clinical Significance

• In a controlled study of a 20-year-old man with a single kidney, creatine supplementation (20g/day for 5 days followed by 5g/day for 30 days) increased serum creatinine from 1.03 mg/dL to 1.27 mg/dL, but did not affect actual kidney function as measured by 51Cr-EDTA clearance 3.
• This false elevation can lead to misdiagnosis of chronic kidney disease with significant personal and public health consequences 1.
• Estimated glomerular filtration rate (eGFR) calculations based on serum creatinine will appear falsely low in individuals taking creatine supplements 3.

Testosterone Supplementation Effects on Serum Creatinine

Mechanism and Impact

• Testosterone supplementation can increase muscle mass and creatine production, which can lead to higher serum creatinine levels 4.
• For transgender individuals on gender-affirming hormone therapy (GAHT) including testosterone, laboratory values should be interpreted based on their affirmed gender after being on GAHT for more than 1 year 4.
• Testosterone therapy can result in nearly 4-kg increase in lean body mass, which affects creatinine generation and serum levels 4.

Clinical Implications for Kidney Function Assessment

Alternative Assessment Methods

• For individuals taking creatine or testosterone supplements, cystatin C may be a better marker for kidney function assessment as it is:
  • Less dependent on muscle mass and dietary intake 4
  • Not affected by creatine supplementation 4
  • More accurate for calculating eGFR in individuals with altered muscle mass 4

Recommendations for Interpretation

• When interpreting laboratory values in individuals taking creatine supplements:

  • Recognize that elevated creatinine may not indicate kidney dysfunction 1
  • Consider using alternative markers of kidney function 4
  • Document supplement use when ordering kidney function tests 1

• For individuals on testosterone therapy:

  • After 1 year of therapy, interpret creatinine values based on affirmed gender 4
  • Consider the duration, dose, and route of administration when interpreting results 4

Safety Considerations

• Creatine supplementation appears safe for individuals with normal kidney function at recommended doses (loading: 20g/day for 5 days; maintenance: ≤3g/day) 5.
• Both supplements should be avoided in people with pre-existing kidney disease or those taking potentially nephrotoxic medications 1, 5.
• If using creatine supplements with high-protein diets, the resulting increase in blood urea nitrogen along with elevated creatinine can further mimic kidney disease 1.

Key Takeaways for Clinical Practice

• Document supplement use when ordering kidney function tests
• Consider alternative markers of kidney function when assessing individuals taking these supplements
• Recognize that elevated creatinine in supplement users may represent a laboratory artifact rather than actual kidney dysfunction
• Use cystatin C-based eGFR calculations when available for more accurate assessment
• Avoid unnecessary diagnostic procedures or treatments based solely on elevated creatinine in supplement users