Does moderate caffeine supplementation affect serum creatinine or renal function in individuals with normal kidney function or chronic kidney disease?

Caffeine Supplementation and Renal Function

Moderate caffeine supplementation does not adversely affect serum creatinine or renal function in individuals with normal kidney function, and may actually be associated with a modest protective effect against chronic kidney disease development. 1, 2

Evidence in Individuals with Normal Kidney Function

Observational Data Supporting Safety

• Daily coffee consumption (1-2+ cups per day) is associated with 16-20% lower risk of developing chronic kidney disease compared to non-drinkers over 11-24 years of follow-up in large prospective cohorts 1, 2

• Each additional cup of coffee consumed per day reduces incident CKD risk by 3% (HR 0.97,95% CI 0.95-0.99) after adjusting for demographics, clinical factors, and dietary variables 2

• Coffee consumption (>6 cups/day) is associated with slightly higher eGFR (1.33-2.47 mL/min/1.73 m² higher) compared to minimal consumption, particularly in individuals aged ≥46 years 3

• Importantly, coffee consumption shows no association with changes in eGFR over time, indicating the higher eGFR is not due to glomerular hyperfiltration (which would suggest kidney damage) 3

Mendelian Randomization and Meta-Analysis

• Mendelian randomization studies using genetic instruments show no causal impact of coffee intake on CKD risk (IVW: β = -0.0191, p = 0.781) or eGFR (β = -0.0005, p = 0.926) in either diabetic or non-diabetic populations 4

• Meta-analysis of 6 studies found no significant association between coffee consumption and CKD (OR 0.85,95% CI 0.71-1.02, p = 0.090) 4

• The convergence of observational protective associations with null causal findings from Mendelian randomization suggests coffee is at minimum safe, and potentially beneficial through unmeasured confounding or non-causal pathways 4

Critical Caveat: Chronic Kidney Disease Populations

Conflicting Evidence in Established CKD

In individuals with pre-existing high-renin hypertension or established kidney disease, prolonged caffeine consumption may accelerate renal function decline 5

• In spontaneously hypertensive heart failure rats (a high-renin hypertension model), 20 weeks of 0.1% caffeine in drinking water accelerated decline in creatinine clearance and increased proteinuria 2-fold compared to controls 5

• At 10 weeks, creatinine clearance was 37% lower in caffeine-treated animals (3.6 vs 5.7 L/kg/day, p<0.02), though by 20 weeks both groups had similarly diminished function 5

• This animal model suggests caffeine may hasten progression in established kidney disease with high renin-angiotensin system activity, though human data in CKD populations are lacking 5

Effect on Serum Creatinine as a Marker

Caffeine's Direct Effects on Creatinine

• Caffeine increases creatinine clearance and urinary creatinine excretion acutely through increased renal blood flow and GFR, which can transiently lower serum creatinine independent of true kidney function changes 6

• This effect is pharmacologic rather than pathologic—caffeine increases urine flow rate, creatinine clearance, and sodium/calcium excretion as part of its diuretic properties 6

Interpretation Considerations

• Serum creatinine alone should never be used to assess kidney function due to multiple confounding factors including muscle mass, age, diet, and medications 7, 8

• Creatinine must be interpreted using validated eGFR equations (MDRD or CKD-EPI), though these have limitations in extremes of age, body size, muscle mass, and rapidly changing kidney function 7, 8

• In individuals consuming caffeine regularly, any acute increase in creatinine clearance would be reflected in steady-state serum creatinine levels, making eGFR calculations still valid for chronic monitoring 7

Practical Recommendations

For Individuals with Normal Kidney Function

• Moderate caffeine consumption (1-3 cups coffee/day, approximately 100-300mg caffeine) poses no risk to kidney function and may provide modest protection against CKD development 1, 2, 3

• No specific monitoring of renal function is required beyond standard clinical care based on age and comorbidities 7

• Creatine supplementation (distinct from caffeine) increases creatinine production without indicating renal dysfunction, so serum creatinine may be falsely elevated in supplement users 8

For Individuals with Established CKD

• Exercise caution with caffeine supplementation in patients with CKD stages 3-5, particularly those with high-renin states (diabetic nephropathy, renovascular disease) 5

• Monitor eGFR and urine albumin-to-creatinine ratio every 3-6 months if caffeine consumption is continued 7, 9

• Consider limiting intake to <200mg/day (approximately 2 cups coffee) until human data in CKD populations clarify safety 5

• Avoid caffeine supplementation entirely in patients with rapidly declining kidney function (>5 mL/min/1.73 m² per year) or nephrotic-range proteinuria (>3.5 g/day) 7, 5

Monitoring Strategy

• Use eGFR calculated from serum creatinine (via CKD-EPI equation) rather than creatinine alone to assess kidney function 7

• Measure urine albumin-to-creatinine ratio on spot morning urine to detect early kidney damage, as values >30 mg/g indicate significant risk 7, 9

• In patients with altered muscle mass, vegetarian diet, or extremes of body size, consider cystatin C-based eGFR as it is less biased by non-renal factors 8