Dataset Information

The Effect of Voriconazole on Tacrolimus in Kidney Transplantation Recipients: A Real-World Study.

ABSTRACT: Tacrolimus is an immunosuppressant with a narrow therapeutic window. Tacrolimus exposure increased significantly during voriconazole co-therapy. The magnitude of this interaction is highly variable, but it is hard to predict quantitatively. We conducted a study on 91 kidney transplantation recipients with voriconazole co-therapy. Furthermore, 1701 tacrolimus concentration data were collected. Standard concentration adjusted by tacrolimus daily dose (C/D) and weight-adjusted standard concentration (CDW) increased to 6 times higher during voriconazole co-therapy. C/D and CDW increased with voriconazole concentration. Patients with the genotype of CYP3A5 *3/*3 and CYP2C19 *2/*2 or *2/*3 were more variable at the same voriconazole concentration level. The final prediction model could explain 54.27% of the variation in C/D and 51.11% of the variation in CDW. In conclusion, voriconazole was the main factor causing C/D and CDW variation, and the effect intensity should be quantitative by its concentration. Kidney transplant recipients with CYP3A5 genotype of *3/*3 and CYP2C19 genotype of *2/*2 and *2/*3 should be given more attention during voriconazole co-therapy. The prediction model established in this study may help to reduce the occurrence of rejection.

SUBMITTER: Zhao YC

PROVIDER: S-EPMC9785881 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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The Effect of Voriconazole on Tacrolimus in Kidney Transplantation Recipients: A Real-World Study.

Zhao Yi-Chang YC Xiao Chen-Lin CL Hou Jing-Jing JJ Li Jia-Kai JK Zhang Bi-Kui BK Xie Xu-Biao XB Fang Chun-Hua CH Peng Feng-Hua FH Sandaradura Indy I Yan Miao M

Pharmaceutics 20221207 12

Tacrolimus is an immunosuppressant with a narrow therapeutic window. Tacrolimus exposure increased significantly during voriconazole co-therapy. The magnitude of this interaction is highly variable, but it is hard to predict quantitatively. We conducted a study on 91 kidney transplantation recipients with voriconazole co-therapy. Furthermore, 1701 tacrolimus concentration data were collected. Standard concentration adjusted by tacrolimus daily dose (C/D) and weight-adjusted standard concentratio ...[more]

PMID: 36559231

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Project description:BackgroundCalcineurin inhibitors, including tacrolimus, remain a cornerstone of immunosuppressive therapy after kidney transplantation. However, the therapeutic window is narrow, and nephrotoxic side effects occur with overdose, while the risk of alloimmunization and graft rejection increases with underdose. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) allows quantification of tacrolimus in biological samples from patients. This study investigates the feasibility of quantifying tacrolimus in scalp hair from kidney transplant (KT) recipients and correlates hair tacrolimus concentrations with tacrolimus dosage and blood trough levels. The aim was to provide proof-of-principle for hair tacrolimus drug monitoring in KT recipients.MethodSingle-center prospective study between September 9, 2021 and December 4, 2021, including KT recipients under tacrolimus. Minors, patients with active skin or hair diseases, and patients with scalp hair shorter than 4 cm were excluded from participation. Scalp hair was collected from the posterior vertex of patients, cut into segments, and analyzed for tacrolimus by LC-MS/MS. Patients filled out a questionnaire on hair treatments and washing habits. In parallel, tacrolimus trough levels were measured in whole blood and correlated with hair tacrolimus concentrations.ResultsIn total, 39 consenting KT recipients were included, and hair samples were collected at 53 visits. Tacrolimus was detected in 98% of hair samples from patients exposed to the drug. Tacrolimus hair levels and whole blood trough levels were correlated with a beta coefficient of 0.42 (95% CI: -0.22-1.1, p = n.s.). Age and dark hair affected hair tacrolimus measurements, while different tacrolimus formulations (immediate release vs. extended release), hair washes, and permanent coloring did not. Longitudinal measurements in a subgroup of patients indicate that long-term measurement of hair tacrolimus levels is feasible.ConclusionMeasuring tacrolimus in hair is a potentially reliable method to monitor drug exposure in KT patients. Rapid wash-in effects and consistent concentrations over time indicate that tacrolimus is incorporated into the hair matrix, allowing temporal resolution in the analysis of recent exposure and exposure history. This method provides a simple and low-risk alternative to regular blood sampling, sparing patients from frequent hospital visits through the self-collection of hair samples.

Project description:BackgroundThe effect of donor kidney morphology parameters on the prognosis of renal transplant recipients remains unclear.MethodsWe conducted a retrospective cohort study consisting of 290 pairs of donors and recipients who underwent living related renal transplantation in our center between December 2013 and December 2015. The donor kidney morphology parameters, demographic characteristics and renal function of the included participants were collected and analyzed.ResultsThe univariate linear regression analysis revealed that the donor kidney weight (DKW)/recipient body weight (RBW), DKW/recipient body surface area (RBSA), DKW/recipient body mass index (RBMI), donor kidney volume (DKV)/RBW, DKV/RBSA, DKV/RBMI, and donor body weight (DBW)/RBW were significantly correlated with estimated glomerular filtration rate (eGFR) and serum creatinine in recipients within two years of transplantation. In our multivariate linear regression analysis, DKW/RBW and donor age significantly correlated with eGFR at 6, 12, 18 and 24 months after transplantation. DKW/RBW had the best prediction performance for good renal allograft function at 12 months after transplantation. We found that when the age of the donor was 55 years and above, the prediction performance of the nephron dosing to the recipient's metabolic demands mismatch was elevated. After grouping according to the donor's age and DKW/RBW, the allograft function from different donor ages improved as DKW/RBW increased. The number of recipients who were rejected in the high DKW/RBW group was significantly fewer than those in the low and medium groups the 1, 2, and 3-year graft and patient survival rates were comparable among these groups. Furthermore, we also identified that when the age of the donor was 55 years and above, the threshold of DKW/RBW was 3.09 g/kg via the receiver operating characteristic curve, which predicted a good renal function 12 months after transplantation.ConclusionsThe donor kidney morphology parameters were significantly associated with early renal allograft function, especially when the age of the donor was 55 years and above.

Dataset Information

The Effect of Voriconazole on Tacrolimus in Kidney Transplantation Recipients: A Real-World Study.

Publications

The Effect of Voriconazole on Tacrolimus in Kidney Transplantation Recipients: A Real-World Study.

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