Early Estimation of Renal Function After Transplantation to Enable Appropriate Dosing of Critical Drugs: Retrospective Analysis of 103 Patients in a Single Center

Publication date

2020-10

Authors

Pieters, Tobias
Beele, Paul
van Zuilen, Arjan D.ORCID 0000-0002-2561-5533ISNI 000000039480153X
Verhaar, Marianne C.ORCID 0000-0002-3276-6428ISNI 0000000390259392
Huitema, Alwin D.R.ISNI 0000000397166009
Rookmaaker, Maarten BISNI 0000000388928841

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Abstract

BACKGROUND: Immediately after renal transplantation (RTX), estimation of renal function (eGFR) is important for drug dosing and the detection of potential complications. Conventional formulas cannot be used since the serum creatinine concentration is not at steady-state. In this study, we evaluated different dynamic renal function formulas (DRFFs) to estimate eGFR immediately after RTX. METHODS: We retrospectively included 154 RTX patients, of whom 45 had delayed graft function (DGF) and required dialysis, and 6 had unstable graft function without the need for dialysis; 103 patients had early, and thereafter stable, graft function (EGF). DRFFs were evaluated to calculate eGFR 1 day after transplantation (T1) using a new dynamic creatinine clearance calculation (D3C), two previously published formulas (Jelliffe, and the kinetic eGFR [KeGFR]), and a naive predictor (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] at T1). The estimated DRFF-based renal functions at T1 were compared with the CKD-EPI after stabilization of renal function 3 days after transplantation (eGFR-T3), which was considered the underlying renal function immediately after RTX. RESULTS: The D3C showed low bias (mean prediction error [MPE] - 4.5 ml/min/1.73 m2) and performed well on other outcome measures (R2 = 0.82, root mean squared error [RMSE] = 11.8 ml/min/1.73 m2, percentage of predictions within 30% of the reference value [p30%] = 76%). In addition, the D3C outperformed the KeGFR (MPE 20.5 ml/min/1.73 m2, R2 = 0.79, RMSE = 26.9 ml/min/1.73 m2, p30% = 29%), Jelliffe (MPE - 13.3 ml/min/1.73 m2, R2 = 0.76, RMSE = 19.1 ml/min/1.73 m2, p30% = 53%), and the naive predictor (bias - 24.8 ml/min/1.73 m2, R2 = 0.60, RMSE = 30.2 ml/min/1.73 m2, p30% = 21%). CONCLUSIONS: The newly developed D3C enables reliable assessment of renal function immediately after RTX, provides crucial information for drug dosing, and might also advance the detection of functional decline, potentially improving treatment and renal outcome.

Keywords

Pharmacology (medical), Pharmacology, Journal Article

Citation

Pieters, T T, Beele, P, Van Zuilen, A D, Verhaar, M C, Huitema, A D R & Rookmaaker, M B 2020, 'Early Estimation of Renal Function After Transplantation to Enable Appropriate Dosing of Critical Drugs : Retrospective Analysis of 103 Patients in a Single Center', Clinical Pharmacokinetics, vol. 59, no. 10, pp. 1303-1311. https://doi.org/10.1007/s40262-020-00893-z