The Tacrolimus Concentration/Dose Ratio Does Not Predict Early Complications After Kidney Transplantation

Transpl Int. 2023 May 9:36:11027. doi: 10.3389/ti.2023.11027. eCollection 2023.

Abstract

Early-on post kidney transplantation, there is a high risk of graft rejection and opportunistic viral infections. A low tacrolimus concentration/dose (C/D) ratio as a surrogate marker of fast tacrolimus metabolism has been established for risk stratification 3 months post-transplantation (M3). However, many adverse events occurring earlier might be missed, and stratification at 1 month post-transplantation (M1) has not been investigated. We retrospectively analyzed case data from 589 patients who had undergone kidney transplantation between 2011 and 2021 at three German transplant centers. Tacrolimus metabolism was estimated by use of the C/D ratio at M1, M3, M6, and M12. C/D ratios increased substantially during the year, particularly between M1 and M3. Many viral infections and most graft rejections occurred before M3. Neither at M1 nor at M3 was a low C/D ratio associated with susceptibility to BKV viremia or BKV nephritis. A low C/D ratio at M1 could not predict acute graft rejections or impaired kidney function, whereas at M3 it was significantly associated with subsequent rejections and impairment of kidney function. In summary, most rejections occur before M3, but a low C/D ratio at M1 does not identify patients at risk, limiting the predictive utility of this stratification approach.

Keywords: BKV nephritis; C/D ratio; acute graft rejection; kidney transplantation; tacrolimus.

MeSH terms

  • Graft Rejection
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Kidney Transplantation* / adverse effects
  • Retrospective Studies
  • Tacrolimus* / adverse effects

Substances

  • Tacrolimus
  • Immunosuppressive Agents

Grants and funding

This study was financially supported by Chiesi GmbH (Hamburg, Germany). The funder was not involved in the study design, data collection, data analysis, or data interpretation, and was not involved in writing and submitting this manuscript. We acknowledge financial support by Land Schleswig-Holstein within the funding programme Open Access Publikationsfonds.