Serum Creatinine and Creatinine Clearance Requirements for Oral PrEP
TDF-based oral PrEP (tenofovir disoproxil fumarate/emtricitabine) is contraindicated when creatinine clearance is below 60 mL/min, and both serum creatinine and estimated creatinine clearance must be assessed before initiating PrEP. 1, 2, 3
Pre-Initiation Requirements
Mandatory Baseline Testing
- Serum creatinine measurement is required before starting any TDF-based PrEP regimen 1, 2
- Calculate creatinine clearance using the Cockcroft-Gault formula (not just eGFR) before initiation 2, 3
- Do not initiate TDF-based PrEP if creatinine clearance is <60 mL/min 1, 2, 3
- Additional baseline assessments should include urine glucose and urine protein in all patients; in those with chronic kidney disease, also measure serum phosphorus 3
Alternative for Renal Impairment
- For cisgender men with creatinine clearance between 30-60 mL/min, switch to TAF/FTC (tenofovir alafenamide/emtricitabine) instead of TDF/FTC 1
- TAF/FTC is specifically indicated for men who have sex with men with moderate renal impairment, but is not recommended for individuals with receptive vaginal exposures or injection drug use alone 1, 4
Ongoing Monitoring Schedule
Standard Monitoring Frequency
- Assess serum creatinine and creatinine clearance at least every 6 months for most PrEP users 1, 2
- This 6-monthly schedule is supported by research showing no qualitative difference in detecting clinically relevant kidney dysfunction compared to 3-monthly monitoring in younger populations 5
Intensified Monitoring for High-Risk Groups
More frequent creatinine monitoring (every 3 months) is warranted for patients with any of the following risk factors: 1, 2
- Age >40-50 years 2, 6
- Taking medications for hypertension or diabetes 1
- Baseline creatinine clearance between 60-90 mL/min 1, 2, 7
- Baseline weight <55 kg 5
- Elevated blood pressure >140 mmHg 5
The evidence strongly supports this risk-stratified approach: older age (≥40 years) carries a 3.79-fold increased risk of developing eGFR <70 mL/min, and baseline eGFR <90 mL/min carries a 9.59-fold increased risk 8. Additionally, individuals with baseline creatinine clearance 60-90 mL/min have an 8.49-fold higher risk of decline to <60 mL/min, and those starting below 60 mL/min have a 20.83-fold higher risk 7.
Clinical Significance of Kidney Function Changes
Expected Changes on TDF-Based PrEP
- Small decreases in creatinine clearance are expected and typically non-progressive after the first 12 weeks 8
- Mean creatinine increases by approximately 0.03 mg/dL (4.6%) and mean creatinine clearance decreases by 4.8 mL/min (3.0%) at week 12, then stabilizes 8
- These changes are generally reversible upon discontinuation 1
When to Discontinue or Adjust
- Stop TDF-based PrEP if confirmed creatinine clearance drops below 60 mL/min 3
- For creatinine clearance 30-49 mL/min: adjust dosing interval to every 48 hours (though this is for treatment, not PrEP) 3
- Consider switching to TAF/FTC for cisgender men if creatinine clearance declines to 30-60 mL/min 1
Important Caveats and Pitfalls
Common Mistakes to Avoid
- Do not rely solely on eGFR calculations—the Cockcroft-Gault creatinine clearance is the required metric for PrEP eligibility and monitoring 2, 3
- Do not use TAF/FTC for individuals with receptive vaginal exposures—insufficient data support its efficacy in this population 1, 4, 9
- Avoid concurrent nephrotoxic agents, particularly high-dose or multiple NSAIDs, which have caused acute renal failure requiring hospitalization in some PrEP users 3
Special Monitoring Considerations
- Persistent bone pain, extremity pain, fractures, or muscle weakness may indicate proximal renal tubulopathy and should prompt immediate renal function evaluation 3
- Approximately 15.7% of PrEP users develop worsening proteinuria at week 12, which typically remains stable thereafter 8
- For patients with hepatitis B coinfection, monitor liver function closely after PrEP discontinuation due to risk of acute hepatitis flares or hepatic decompensation 1, 2