What are the risks of creatine monohydrate supplementation in patients with chronic kidney disease or reduced glomerular filtration rate?

Risks of Creatine Monohydrate Supplementation

Creatine monohydrate supplementation is generally safe for healthy individuals but should be avoided in patients with pre-existing chronic kidney disease (CKD), reduced glomerular filtration rate (GFR <45 mL/min/1.73 m²), diabetes, hypertension, or those with a solitary kidney. 1, 2

Key Safety Considerations by Patient Population

Patients with Normal Kidney Function

• Creatine supplementation does not impair kidney function in healthy individuals, even with long-term use (up to 5 years) at doses ranging from 5-30 g/day 2, 3
• Short-term and long-term supplementation shows no significant effects on glomerular filtration rate, urea production, or albumin excretion in healthy populations 2, 3
• The primary risk in healthy individuals is diagnostic confusion rather than actual kidney damage 1, 4

Patients with Reduced Kidney Function

• Individuals with eGFR <45 mL/min/1.73 m² should avoid creatine entirely 1
• Patients with serum creatinine ≥2 mg/dL or reduced GFR are at higher risk for postoperative renal dysfunction and increased long-term morbidity and mortality 5
• Those with diabetes and kidney disease should not use creatine supplementation, particularly when eGFR <45 mL/min/1.73 m² 1

Patients with Solitary Kidney

• The American Journal of Kidney Diseases explicitly discourages creatine supplementation in kidney donors and individuals with a solitary kidney due to the critical need to preserve remaining renal function 1
• This recommendation stems from the principle that any substance with uncertain effects on kidney function should be avoided when renal reserve is already compromised 1
• One case study showed no change in measured GFR (51Cr-EDTA clearance) in a young man with a single kidney after 35 days of creatine supplementation, though serum creatinine increased from 1.03 to 1.27 mg/dL 6

Diagnostic Pitfalls and Monitoring Challenges

False Elevation of Serum Creatinine

• Creatine supplementation increases serum creatinine by 0.2-0.3 mg/dL through non-pathologic conversion to creatinine, creating a false appearance of acute kidney injury 1, 4
• eGFR formulas incorporating serum creatinine are unreliable in patients with high muscle mass or those taking creatine supplements 1
• eGFR calculations assume steady-state conditions and are invalid when creatinine is acutely elevated from non-renal causes such as creatine supplementation and intense exercise 1
• This can lead to misdiagnosis of chronic kidney disease when none exists 1, 4

Appropriate Diagnostic Approach

• Serum creatinine alone should never be used to assess kidney function due to confounding factors like muscle mass and creatine metabolism 1
• Obtain urinalysis with microscopy to look for proteinuria, hematuria, cellular casts, or acanthocytes that would indicate true intrinsic kidney disease 1
• Check spot urine albumin-to-creatinine ratio, as albuminuria indicates glomerular damage and true kidney disease 1
• Consider cystatin C measurement as an alternative marker of kidney function that is not affected by muscle mass or creatine supplementation 1
• CKD requires evidence of kidney damage or reduced GFR persisting for at least 3 months 1
• A single elevated creatinine in the context of creatine supplementation and recent exercise does not establish CKD diagnosis 1

Management When Creatine-Related Kidney Concerns Arise

Immediate Steps

• Discontinue creatine supplementation immediately if there is diagnostic uncertainty about kidney function 1
• Repeat serum creatinine and GFR measurements within 1-2 weeks after cessation of creatine to assess true baseline kidney function 1
• Avoid other potentially nephrotoxic medications such as NSAIDs, which can further worsen renal function 5, 1

Monitoring Protocol

• Check serum creatinine, potassium, and GFR within 2-4 weeks after discontinuation of creatine supplements 1
• For patients with GFR between 30-44 mL/min/1.73 m² (Stage 3b CKD), regular monitoring of renal function every 3-6 months is recommended 1
• Use cystatin C-based GFR or measured GFR rather than serum creatinine or creatinine-based eGFR during creatine supplementation 1

When to Refer to Nephrology

• Refer to nephrology when eGFR falls below 30 mL/min/1.73 m² or when there is rapidly progressive kidney disease 5, 1
• If renal function continues to decline despite discontinuation of creatine, nephrology referral is warranted 1
• Nephrology consultation is required before initiating creatine in patients with pre-existing kidney disease 1

Rare but Documented Adverse Events

Acute Tubular Necrosis

• One case report documented acute tubular necrosis in an 18-year-old man taking recommended doses of creatine monohydrate, presenting with nausea, vomiting, and stomach pain 7
• The patient recovered fully 25 days after stopping creatine supplementation 7
• This represents the only documented case of acute tubular necrosis associated with creatine at recommended doses, though causality cannot be definitively established 7

Gastrointestinal and Muscle Complaints

• Anecdotal reports from athletes include muscle cramps and gastrointestinal complaints during creatine supplementation, but the incidence is limited and not necessarily linked to creatine itself 2

Contraindications and High-Risk Scenarios

Absolute Contraindications

• Pre-existing renal disease (serum creatinine ≥2 mg/dL or eGFR <45 mL/min/1.73 m²) 1, 2
• Solitary kidney status 1
• Active kidney disease with proteinuria or hematuria 1

Relative Contraindications Requiring Caution

• Diabetes mellitus, particularly with any degree of nephropathy 1, 2
• Hypertension, especially if poorly controlled 1, 2
• Concurrent use of potentially nephrotoxic medications (NSAIDs, aminoglycosides) 5, 1
• High-protein diet (>1.3 g/kg/day) combined with creatine supplementation 1, 4

Practical Clinical Recommendations

Pre-Supplementation Assessment

• While pre-supplementation investigation of kidney function might be considered for safety reasons, it appears unnecessary in normal healthy subjects 2
• For individuals with risk factors (diabetes, hypertension, family history of kidney disease), baseline kidney function testing is prudent 1, 2

Dietary Considerations

• Maintain consistent hydration before creatinine testing to avoid dehydration-related elevations 1
• Avoid intense exercise 24 hours prior to creatinine testing, as muscle breakdown releases creatinine 1
• Consider fasting from meat for 12-24 hours before creatinine testing to avoid dietary effects 1

Drug Interactions

• Small increases in creatinine (up to 30% from baseline) with ACE inhibitors or ARBs should not be confused with creatine-induced changes and do not warrant medication discontinuation in the absence of volume depletion 5, 1
• Combining creatine with other nephrotoxic exposures such as NSAIDs or high-dose protein should be avoided 1