Longitudinal Exposure to Tacrolimus and New-Onset Diabetes Mellitus in Renal Transplant Patients. Issue 1 (February 2023)

• Record Type: Journal Article
• Authors: Destere, Alexandre; Premaud, Aurélie; Monchaud, Caroline; Marquet, Pierre; Woillard, Jean-Baptiste
• Is Part Of: Therapeutic drug monitoring. Volume 45:Issue 1(2023)
• Page Start: 102
• Page End: 109
• Publication Date: 2023-02
• Subjects: tacrolimus -- diabetes mellitus -- renal transplant -- exposure -- Cox model; Pharmacokinetics -- Periodicals; Patient monitoring -- Periodicals; Drugs -- Analysis -- Periodicals; Body fluids -- Analysis -- Periodicals; Drug Therapy -- Periodicals; Monitoring, Physiologic -- Periodicals; Pharmacology -- Periodicals; 615.7
• DOI: 10.1097/FTD.0000000000001035
• Languages: English
• ISSNs: 0163-4356

Abstract

Abstract : Supplemental Digital Content is Available in the Text. Abstract : Purpose: Tacrolimus is an immunosuppressant widely used in transplantations requiring mandatory concentration-controlled dosing to prevent acute rejection or adverse effects, including new-onset diabetes mellitus (NODM). However, no relationship between NODM and tacrolimus exposure has been established. This study aimed to evaluate the relationship between cumulative tacrolimus exposure and NODM occurrence. Methods: A total of 452 kidney transplant patients were included in this study. Sixteen patients developed NODM during the first 3 months after transplant. We considered all tacrolimus concentration (C0) values collected until the diagnosis of NODM in these patients and until 3 months after transplant in the others. New tacrolimus cumulative exposure metrics were derived from the time profile of the tacrolimus morning predose concentration, C0: the percentage of C0 values > cutoff, the average of C0 values above the cutoff, and the percentage of the area under C0 versus time curve, AUCC0, above the cutoff. The cutoff chosen was 15 ng/mL, corresponding to the higher end of the therapeutic range for the early post-transplant period. The influence of these metrics on NODM and other clinical and biological characteristics was investigated using the Cox models. Results: The percentage of C0 > 15 mcg/L was statistically different between patients with and without NODM ( P = 0.01). Only these tacrolimus C0-derived metrics were significantly associated with an increased risk of NODM [HR: 1.73 (1.43–2.10, P < 0.001)]. Conclusion: This study shows that tacrolimus concentrations >15 mcg/L affect the incidence of NODM.