J Korean Surg Soc.  2010 Dec;79(6):428-435. 10.4174/jkss.2010.79.6.428.

Optimized Tacrolimus Therapy in the Early Stage after Renal Transplantation

• Min SI
• Kim SY
• Ahn SH
• Chung CK
• Min SK
• Ha J
• Kim SJ

• KMID: 2096597
• DOI: http://doi.org/10.4174/jkss.2010.79.6.428

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.

Keyword

Kidney transplantation; Tacrolimus; Trough concentration; Acute rejection; Graft function

MeSH Terms

Adult
Glomerular Filtration Rate
Graft Rejection
Humans
Immunosuppression
Incidence
Kidney Transplantation
Rejection (Psychology)
Tacrolimus
Transplants
Tacrolimus

Figure

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  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.

• 

  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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