Association of Intrapatient Variability of Tacrolimus Concentration With Early Deterioration of Chronic Histologic Lesions in Kidney Transplantation

Hyejin Mo, MD; Song-Yi Kim, MD; Sangil Min, MD, PhD; Ahram Han, MD; Sanghyun Ahn, MD; Seung-Kee Min, MD; Hajeong Lee, MD; Curie Ahn, MD; Yonsu Kim, MD; Jongwon Ha, MD, PhD

doi:10.1097/TXD.0000000000000899

Transplantation Direct (Jun 2019)

Association of Intrapatient Variability of Tacrolimus Concentration With Early Deterioration of Chronic Histologic Lesions in Kidney Transplantation

Hyejin Mo, MD,
Song-Yi Kim, MD,
Sangil Min, MD, PhD,
Ahram Han, MD,
Sanghyun Ahn, MD,
Seung-Kee Min, MD,
Hajeong Lee, MD,
Curie Ahn, MD,
Yonsu Kim, MD,
Jongwon Ha, MD, PhD

Affiliations

Hyejin Mo, MD: 1Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
Song-Yi Kim, MD: 1Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
Sangil Min, MD, PhD: 1Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
Ahram Han, MD: 1Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
Sanghyun Ahn, MD: 1Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
Seung-Kee Min, MD: 1Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
Hajeong Lee, MD: 2Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Curie Ahn, MD: 2Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Yonsu Kim, MD: 2Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Jongwon Ha, MD, PhD: 1Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.

DOI: https://doi.org/10.1097/TXD.0000000000000899
Journal volume & issue: Vol. 5, no. 6
p. e455

Abstract

Read online

Background. High intrapatient variability (IPV) of tacrolimus (Tac) is increasingly recognized as a risk factor for poor graft outcomes in kidney transplantation. The timing of onset of its impact on kidney histologic lesions has not been investigated. Methods. We analyzed the adverse effect of Tac IPV using the coefficient of variability from 6 to 12 months posttransplantation on long-term outcomes in a cohort of 671 kidney recipients and on the evolution of chronic histologic lesions in a cohort of 212 recipients for whom paired protocol biopsies at 10 days and 1 year were available. Results. High IPV of Tac (cutoff value of coefficient of variability = median of 20.5%) was associated with an increased risk of graft loss (hazard ratio, 3.28; 95% confidence interval, 1.090–9.849; P = 0.035) in the entire cohort. At 1 year, the high Tac IPV group showed a significantly deteriorated chronicity score (F = 5.912, P = 0.016) compared with the low Tac IPV group in the Histology cohort after controlling for the 10-day scores. In a multivariate analysis, a high IPV of Tac was predictive of the chronicity score (odds ratio, 1.91; 95% confidence interval, 0.215–1.075; P = 0.003) at 1 year posttransplant. Conclusions. These data indicate that high IPV of Tac is associated with early deterioration of chronic histologic lesions as well as poorer long-term outcomes. Large prospective studies of Tac IPV usage as a clinical monitoring tool are needed in the future.

Published in Transplantation Direct

ISSN: 2373-8731 (Online)
Publisher: Wolters Kluwer
Country of publisher: United States
LCC subjects: Medicine: Surgery
Website: http://journals.lww.com/transplantationdirect/Pages/default.aspx

About the journal