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Min, Kim, Ahn, Chung, Min, Ha, and Kim: Optimized Tacrolimus Therapy in the Early Stage after Renal Transplantation
Original Article
Journal of the Korean Surgical Society

Journal of the Korean Surgical Society 2010; 79(6): 428-435.

Published online: 31 December 2010

DOI: https://doi.org/10.4174/jkss.2010.79.6.428

Optimized Tacrolimus Therapy in the Early Stage after Renal Transplantation

Sang-Il Min, M.D., Seong Yup Kim, M.D., Sang Hyun Ahn, M.D., Chin Koo Chung, M.D., Seung-Kee Min, M.D., Jongwon Ha, M.D., Sang Joon Kim, M.D.

Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.

Corresponding author (sjkimgs@plaza.snu.ac.kr)

Received 12 August 2010       Accepted 19 October 2010

Copyright © 2010 The Korean Surgical Society

Abstract

Purpose

Immunosuppressive regimen based on reduced-dose Tacrolimus (TAC) is widely accepted in the field of renal transplantation. However, optimal targetsfor TAC whole blood trough concentrations during the early period after kidney transplantation remain uncertain.

Methods

A total of 184 consecutive adult renal transplant recipients with triple immunosuppression (TAC/Mycophenolate/corticosteroid) were included in this study. According to the trough level of TAC at day 7 after transplantation, patients were classified as low TAC concentration (LT, <10 ng/ml, n=85), intermediate TAC concentration (IT, 10~15 ng/ml, n=75), and high TAC concentration (HT, >15 ng/ml, n=24) groups. Rate of acute rejection, graft function and side effects of TAC within 1 yr after transplantation were evaluated.

Results

There was no difference in trough concentrations of TAC at 2 weeks, 1 month, 3 months, 6 months and 12 months after transplantation among the three groups. Significantly higher incidence of acute rejection within 2 weeks after transplantation was observed in LT group compared with IT and HT groups (17.4%, 5.6% and 4.8%, respectively, P=0.037). HT patients showed significantly better estimated glomerular filtration rates until 6 months after transplantation than IT and LT patients (75.5±24.8 vs. 63.8±12.8 and 64.3±15.2 ml/min at 6 months, P=0.03). There was no significant difference in TAC toxicity in terms of post-transplant diabetes and renal toxicity.

Conclusion

Short-term high TAC exposure immediately after kidney transplantation may provide lower incidence of acute rejection and better restoration of graft function compared with low or intermediate TAC exposure.

Keywords: Kidney transplantation, Tacrolimus, Trough concentration, Acute rejection, Graft function

Figures and Tables

Fig. 1
Changes in tacrolimus trough level. (A) Tacrolimus trough levels were gradually tapered to 6~8 ng/ml at 1 year after transplantation. (B) Patients were classified according to tacrolimus trough level at 7 days after transplantation. LT = low tacrolimus group (FK<10 ng/ml, n=85); IT = intermediate tacrolimus group (FK 10~15 ng/ml, n=75); HT = high tacrolimus group (FK>15 ng/ml, n=24). *P<0.001.
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Fig. 2
Incidences of acute rejection. (A) Cumulative probability of acute rejection and (B) frequencies (%) of acute rejection within 2 weeks after transplantation. *P<0.05.
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Fig. 3
Changes in eGFR. (A) HT group showed significantly improved graft function until 6 months after transplantation compared to LT and IT patients and (B) until 12 months after transplantation in analysis of LDKT recipients. *P<0.05; †P<0.01.
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Fig. 4
Tacrolimus toxicity within 1 year after transplantation according to tacrolimus trough levels at 7 days after transplantation. (A) The frequency (%) of tacrolimus renal toxicity identified and (B) Post-transplant diabetes mellitus developed. There were no significant differences among study groups.
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Table 1
Demographic and baseline characteristics of study population
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*POD = postoperative day; †BMI = Body mass index; ‡ESRD = end-stage renal disease; §CGN = chronic glomerulonephritis; ∥HLA = human leukocyte antigen; LDKT = live donor kidney transplantation; **DDKT = deceased donor kidney transplantation.

Table 2
Univariate and multivariate analysis findings for risk factors of early acute rejection within 2 weeks after kidney transplantation
jkss-79-428-i002

*The other variables that did not meet criteria (P<0.10) for inclusion into the multivariate analysis were recipient body mass index (P=0.792), retransplantation (P=0.785) and duration of dialysis (P=0.302). †OR = odds ratio; ‡CI = confidence interval; §DDKT = deceased donor kidney transplantation; ∥HLA = human leukocyte antigen; HT = high tacrolimus.

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