Management of Mild Creatinine Elevation in PrEP User
Reassure the patient that this increase can be transient and check for proteinuria today, then recheck kidney function in 1 to 3 months. 1, 2, 3
Rationale for This Approach
The observed creatinine increase from 0.80 to 1.00 mg/dL (a 0.20 mg/dL or 25% increase) with CrCl remaining above 60 mL/min represents an expected, typically transient change associated with TDF-based PrEP initiation that does not require discontinuation. 4, 5
Why This Change is Expected and Generally Benign
Mean creatinine increases of 0.03 mg/dL (4.6%) occur by week 12 of TDF/FTC PrEP and stabilize thereafter without progression. 4
Small declines in CrCl (approximately 2-3 mL/min) are documented in placebo-controlled trials and reverse within 4 weeks of discontinuation if PrEP is stopped. 5, 6
This change reflects tubular secretion effects rather than true glomerular injury—TDF inhibits creatinine tubular secretion, causing creatinine to rise without actual kidney damage. 4, 5
More than 96% of participants show >75% eGFR rebound to baseline within 8 weeks after drug discontinuation, confirming reversibility. 5
Why Proteinuria Assessment is Critical Today
The CDC and NIH recommend checking for proteinuria when creatinine changes occur during PrEP monitoring to identify the rare cases of true proximal tubular dysfunction. 2, 3
Approximately 15.7% of PrEP users develop worsening proteinuria at week 12, though this typically remains stable and nonprogressive. 4
Proteinuria provides additional prognostic information about kidney function and helps distinguish benign creatinine elevation from clinically significant kidney injury. 7
Why PrEP Should NOT Be Stopped
TDF-based PrEP is only contraindicated when CrCl falls below 60 mL/min—this patient remains above that threshold. 1, 8
The FDA label specifies dose adjustment or discontinuation only when CrCl drops to <50 mL/min, not for mild elevations with CrCl >60 mL/min. 8
Stopping PrEP prematurely exposes the patient to HIV acquisition risk without medical justification, as these changes are typically nonprogressive after 12 weeks. 4, 9
Appropriate Monitoring Schedule Going Forward
Increase creatinine monitoring frequency to every 3 months (rather than every 6 months) for this patient, as she now has a risk factor for kidney changes. 1, 2, 3
The CDC and NIH recommend more frequent monitoring (every 3-6 months) for patients with baseline CrCl <90 mL/min or those who develop creatinine changes. 2, 3
Continue quarterly HIV testing, STI screening, and adherence counseling as per standard PrEP protocols. 2, 3
Risk Stratification for Future Monitoring
Independent predictors of developing eGFR <70 mL/min include age ≥40 years (OR 3.79) and baseline eGFR <90 mL/min (OR 9.59). 4
Older individuals (>50 years), those with diabetes, hypertension, or baseline CrCl <90 mL/min require closer monitoring every 3 months. 1, 2, 9
Younger individuals without comorbidities and baseline CrCl >90 mL/min can continue standard 6-month monitoring if creatinine stabilizes. 9
Common Pitfalls to Avoid
Do not discontinue PrEP based solely on mild creatinine elevation with CrCl >60 mL/min—this represents overreaction to expected pharmacologic effects. 1, 4, 5
Do not delay proteinuria assessment—checking today allows early detection of the rare cases requiring intervention. 2, 3, 4
Do not refer to nephrology at this stage unless proteinuria is significant or CrCl continues declining below 60 mL/min on repeat testing. 1, 8
Do not simply "reassure and recheck in 1-3 months" without checking proteinuria today—this misses the opportunity to identify true tubular dysfunction early. 2, 3