Longitudinal Exposure to Tacrolimus and New-Onset Diabetes Mellitus in Renal Transplant Patients

• Published in: Therapeutic drug monitoring Vol. 45; no. 1; p. 102
• Main Authors: Destere, Alexandre, Premaud, Aurélie, Monchaud, Caroline, Marquet, Pierre, Woillard, Jean-Baptiste
• Format: Journal Article
• Language: English
• Published: United States 01.02.2023
• Subjects: Diabetes Mellitus - chemically induced; Drug-Related Side Effects and Adverse Reactions; Humans; Immunosuppressive Agents - adverse effects; Kidney Transplantation - adverse effects; Tacrolimus - adverse effects
• ISSN: 1536-3694
• DOI: 10.1097/FTD.0000000000001035

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. 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. 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)]. This study shows that tacrolimus concentrations >15 mcg/L affect the incidence of NODM.