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Tacrolimus-related adverse effects in liver transplant recipients: Its association with trough concentrations

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Indian Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

Tacrolimus is an important immunosuppressant administered to patients following liver transplantation (LT), with a recommended trough concentration of 8 to 11 ng/mL to prevent allograft rejection. We retrospectively examined our data to identify the tacrolimus trough concentration that combined efficacy with minimal adverse effects.

Methods

The case records of LT recipients, who were nondiabetic, nonhypertensive, and with normal renal parameters prior to LT were retrospectively examined for acute cellular rejection (ACR) episodes and three major adverse effects of tacrolimus, i.e. neurotoxicity, nephrotoxicity, and new onset diabetes mellitus (NODM).

Results

Thirty-two LT recipients fulfilled the criteria for the study. The mean (±SD) tacrolimus level for the 290 troughs (after 10 days) was 8.5 ± 3.8 ng/mL. At 10 days, 1 month, 3 months, and 6 months, the trough values were 7.3 ± 2.9, 9.7 ± 3.4, 7.9 ± 3.3, and 7.6 ± 2.6 ng/mL, respectively. The mean time taken for stabilization of the blood pressure and biochemical parameters was 7 ± 2 days. Overall, a trough window with the least adverse effect was 7 to 7.9 ng/mL. Neurotoxicity was least in the trough range 5 to <8 ng/mL. Symptoms included headache in four, tremors in three, seizure in one, confusion and psychosis in two, and combination in three. Nephrotoxicity was least in trough 8 to <11 ng/mL. One patient progressed to chronic kidney disease at 6 months. NODM was present in 11 % to 18 % across the various trough range, including the extremes (mean trough level, 8.4 ± 4.4 ng/dL). At 6 months, five recipients were on treatment for NODM. Three recipients developed ACR, two within the first month and one at 7 weeks. The trough levels were 8.5, 9, 15.2 ng/mL, respectively. All recovered with three pulse doses of methylprednisolone.

Conclusion

Tacrolimus concentration of 5 to <8 ng/mL was associated with least overall toxicity, neurotoxicity, and ACR.

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Acknowledgments

The authors acknowledge the assistance of liver transplant coordinators, Mr. Santosh and Mr. Augustaine for retrieving data from patient records and Mr. Sri Hari, Research Coordinator in data analysis.

Conflict of interest

JV, MSR, KV, RP, GN, OA, VS, NS, VS, VJ and MR all declare that they have no conflict of interest.

Ethics statement

The authors declare that the study was performed in a manner to conform with the Helsinki Declaration of 1975, as revised in 2000 and 2008 concerning Human and Animal Rights, and that the authors followed the policy concerning Informed Consent as shown on www.Springer.com.

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Authors and Affiliations

  1. Department of Hepatology and Liver Transplantation, Global Hospitals and Health City, 439, Cheran Nagar, Perumbakkam, Chennai, 600 100, India

    Joy Varghese, Olithselvan Arikichenin, Naresh Shanmugam, Vijaya Srinivasan, Venkataraman Jayanthi & Mohamed Rela

  2. Institute of Hepatopancreaticbiliary and Transplantation, Global Hospitals and Health City, 439, Cheran Nagar, Perumbakkam, Chennai, 600 100, India

    Mettu Srinivasa Reddy, Kota Venugopal, Rajasekhar Perumalla, Gomathy Narasimhan, Vivekanandan Shanmugam & Mohamed Rela

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  1. Joy Varghese
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Correspondence to Joy Varghese.

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Varghese, J., Reddy, M.S., Venugopal, K. et al. Tacrolimus-related adverse effects in liver transplant recipients: Its association with trough concentrations. Indian J Gastroenterol 33, 219–225 (2014). https://doi.org/10.1007/s12664-014-0456-0

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  • DOI: https://doi.org/10.1007/s12664-014-0456-0

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