Creatine supplementation confounding kidney function monitoring in tenofovir-based HIV preexposure prophylaxis

Abstract Introduction Tenofovir‑based preexposure prophylaxis (PrEP) is widely used and proved its efficacy for HIV prevention, and kidney function monitoring relies primarily on serum creatinine-based estimation of the glomerular filtration rate (eGFR). Oral creatine supplementation can increase serum creatinine without reflecting a true reduction in glomerular filtration rate (GFR). As is not widely known it can potentially lead to inappropriate PrEP discontinuation. Case description We report three clinical cases of healthy men who have sex with men (MSM) receiving tenofovir‑based PrEP who referred to a nephrologist for declining serum creatinine‑based eGFR while taking oral creatine supplements for muscle development associated with sport. Serum creatinine compared to cystatin C-based eGFR was performed and measured GFR (DTPA‑Tc99) when available to assess kidney function. In the first case, a 45‑year‑old man taking daily PrEP and oral creatine presented with elevated serum creatinine (1.39 mg/dl) and reduced creatinine‑based eGFR (61 ml/min/1.73 m2). Cystatin C-based eGFR indicated a preserved kidney function (83 ml/min/1.73 m2). After discontinuing creatine, serum creatinine decreased to 1.17 mg/dl and creatinine‑based eGFR improved to 75 ml/min/1.73 m2, aligning with cystatin C estimates. In the second case, a 38‑year‑old man using on‑demand PrEP and taking oral creatine referred to the nephrologist with a decline in creatinine‑based eGFR from 112 to 78 ml/min/1.73 m2 over four years. Despite this apparent decline, measured GFR was in range (113 ml/min/1.73 m2) aligned with cystatin C-based eGFR (107 ml/min/1.73 m2). In the third case, a reduced creatinine-based eGFR was observed in a 41‑year‑old man who was taking daily PrEP with the supplement. Moreover, a one‑day interruption of creatine prevented this artifact, with both serum creatinine and cystatin C returning to normal ranges. A last serum creatinine measurement performed four days after creatine was reintroduced reduced the eGFR by 20 ml/min/1.73 m2. Discussion Oral creatine supplementation, frequently used by tenofovir-based PrEP users, can artifactually elevate serum creatinine and lead to underestimation of kidney function. Cystatin C-based eGFR is not affected by creatine and so its use can be an easy tool for PrEP prescribers for an accurate assessment of kidney function. Its use may prevent risky and unjustified PrEP interruptions and reduce nephrological referral. Creatine metabolism permits a withdrawal one day before the PrEP follow-up lab tests.