RESUMEN
BACKGROUND: Clinicians caring for kidney transplant recipients (KTRs) most commonly use estimated glomerular filtration rate (eGFR) to guide medication dosing as it is the most readily available measure of kidney function. Which eGFR equations provide the most accurate medication dosing guidance for KTRs remains uncertain. METHODS: We studied 415 stable KTRs in Canada and New Zealand. Participants completed same-day measurements of creatinine and cystatin C and measured GFR (diethylenetriaminepentaacetic acid). Chronic Kidney Disease Epidemiology Collaboration, European Kidney Function Consortium, and transplant-specific eGFR equations were compared with both Cockcroft-Gault creatinine clearance (CrCl) and measured GFR. eGFR equations were assessed both indexed to a standardized body surface area (BSA) of 1.73 m2 (milliliter per minute per 1.73 m2, as is conventional reporting from most clinical laboratories) and nonindexed (milliliter per minute) accounting for actual BSA. The primary outcome was the proportion of medication dosing discordance relative to Cockcroft-Gault CrCl or measured GFR for 8 commonly prescribed medications. Stratified analyses were performed on the basis of obesity status. RESULTS: Nonindexed eGFR equations (milliliter per minute) resulted in substantially lower medication dosing discordance compared with indexed eGFR equations (milliliter per minute per 1.73 m2). These findings were most pronounced among KTRs with obesity, in whom underdosing was frequent. When compared with Cockcroft-Gault CrCl, the lowest proportion of discordance was found with the nonindexed 2023 transplant-specific equation. When compared with measured GFR, the lowest proportion of discordance was found with the nonindexed 2021 Chronic Kidney Disease Epidemiology CollaborationCr/CysC equation. CONCLUSIONS: Nonindexed eGFR values accounting for actual BSA should be used by clinicians for medication dosing in KTRs. These findings may inform KT providers about which eGFR equations provide the safest, most accurate medication dosing guidance for KTRs.
RESUMEN
BACKGROUND: Nirmatrelvir/ritonavir has been shown to reduce the risk of COVID-19 related complications in patients at high risk for severe COVID-19. However, clinical experience of nirmatrelvir/ritonavir in the transplant recipient population is scattered due to the complex management of drug-drug interactions with calcineurin inhibitors. We describe the clinical experience with nirmatrelvir/ritonavir at The Ottawa Hospital kidney transplant program. METHODS: Patients who received nirmatrelvir/ritonavir between April and June 2022 were included and followed up 30 days after completion of treatment. Tacrolimus was withheld for 24 hours and resumed 72 hours after the last dose of nirmatrelvir/ritonavir (on Day 8) based on drug level the day before. The first 30 patients had their dose adjusted according to drug levels performed twice in the first week and as needed thereafter. Subsequently, a simplified algorithm with less frequent calcineurin inhibitor level monitoring was implemented. Outcomes including tacrolimus level changes, serum creatinine and acute kidney injury (AKI, defined as serum creatinine increase by 30%) and clinical outcomes were described globally and compared between algorithms. RESULTS: Fifty-one patients received nirmatrelvir/ritonavir. Tacrolimus levels drawn at the first timepoint, 7 days after withholding of calcineurin inhibitor and 2 days after discontinuing nirmatrelvir/ritonavir were within the therapeutic target in 17/44 (39%), subtherapeutic in 21/44(48%) and supratherapeutic in 6/44 (14%). Two weeks after, 55% were within the therapeutic range, 23% were below, and 23% were above it. The standard and simplified algorithms provided similar tacrolimus level (median 5.2 ug/L [4.0, 6.2] versus 4.8 ug/L [4.3, 5.7] p=0.70). There were no acute rejections or other complications. CONCLUSIONS: Withholding tacrolimus starting the day before initiation of nirmatrelvir/ritonavir with resumption 3 days after completion of therapy resulted in a low incidence of supratherapeutic levels but a short period of subtherapeutic levels for many patients. AKI was infrequent. The data are limited by the small sample size and short follow-up.