Creatine Supplementation and Kidney Function

Understanding the Mechanism

The KDIGO guidelines identify "high-protein diets and creatine supplements" as causes of non-GFR determinants of serum creatinine that reduce the accuracy of creatinine-based eGFR equations, affecting individuals with normal or mildly reduced kidney function 1, 2
Creatine supplementation affects creatinine generation—a non-GFR determinant—not actual kidney function, which can lead to misdiagnosis of kidney disease in patients with normal kidney function 1, 2

When evaluating kidney function in patients taking creatine supplements, the KDIGO guidelines recommend using cystatin C-based eGFR (eGFRcys) or combined creatinine-cystatin C equations (eGFRcr-cys) rather than creatinine-based eGFR alone, to avoid misdiagnosis of kidney disease 1, 2, 3
For patients on creatine supplements, eGFRcys is the preferred initial alternative since it is not affected by creatine metabolism, according to the Kidney International guidelines 1, 2
If precise GFR measurement is needed for critical clinical decisions, measuring GFR directly using plasma or urinary clearance of exogenous filtration markers is recommended by the American Journal of Kidney Diseases 1, 3

If a patient is on creatine and eGFRcr appears reduced, ordering cystatin C and calculating eGFRcys or eGFRcr-cys is recommended by the Kidney International and American Journal of Kidney Diseases guidelines 1, 2, 3
If eGFRcys is also reduced, investigating for true kidney disease with additional testing (urinalysis, imaging, etc.) is necessary, as suggested by the Kidney International and American Journal of Kidney Diseases guidelines 1, 3

The American Heart Association recommends that individuals with severely decreased kidney function, such as an eGFR of 29 mL/min/1.73m², avoid substances that may further impair kidney function, including creatine supplementation 4, 5
Individuals with an eGFR of 29 mL/min/1.73m² are classified as having Stage 4 Chronic Kidney Disease, indicating severely decreased kidney function 5, 6

The European Society of Cardiology notes that creatine supplementation can increase the filtration burden on the kidneys, potentially exacerbating existing kidney impairment 5
The American College of Cardiology recommends that individuals with an eGFR <30 mL/min/1.73m² avoid medications and supplements that increase renal workload, including creatine supplementation 4, 7

The American Diabetes Association recommends regular monitoring of kidney function parameters, such as creatinine and eGFR, in individuals with impaired kidney function 8
The European Society of Cardiology suggests that individuals with severely impaired kidney function consider dietary protein intake of approximately 0.8 g/kg body weight per day and optimize blood pressure control if hypertensive 8
The American Heart Association advises individuals with an eGFR of 29 mL/min/1.73m² to consult with a nephrologist for comprehensive kidney care and to avoid other nephrotoxic medications and supplements 5, 8