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Combination therapy with diltiazem plus CsA/MMF/Pred or CsA/Aza/Pred triple immunosuppressive regimens for use in clinical kidney transplantation in Northwestern China

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Abstract

Objective

The effects of diltiazem on 1692 kidney transplant recipients under the immunosuppressive regimen of cyclosporine A (CsA) in combination with either mycophenolate mofetil or azothioprine were assessed. The two treatment groups were compared for blood concentrations of CsA, the extent of acceptable dosage reduction for the maintenance of immunotherapy, potential effects of kidney protection, and promotion of graft function.

Method

We monitored changes of blood concentrations of CsA in the two different patient treatment groups for post-transplant graft function, episodes of acute rejection, and hepatic and renal toxicity in 1640 renal transplant recipients after treatment with diltiazem.

Results

In patients treated with the triple immunosuppressive regimen consisting of CsA, azothioprine, and prednisolone (Pred), the sub-group of patients receiving the diltiazem treatment saw a significantly reduced CsA dosage in comparison to the non-diltiazem group (control group 1) (P < 0.05), but the blood concentrations of CsA of the diltiazem group were higher than those of control group 1 (P < 0.01). Of the patients treated with CsA, mycophenolate mofetil, and Pred, the sub-group of patients also treated with diltiazem showed similar effects: CsA dosage was reduced (P < 0.01) and the blood concentrations of CsA significantly increased (P < 0.01) in comparison with those of control group 2. In addition, recovery time of graft function decreased to 4.7 ± 1.8 days and 3.9 ± 1.4 days in the two diltiazem treatment groups, respectively (P < 0.05), and the rate of acute rejection decreased to 21 (p < 0.05) and 7.9% (P < 0.01), respectively.

Conclusion

In our cohort of renal transplantation patients, co-administration of CsA and diltiazem increased CsA blood concentration, thereby resulting in a reduction in its required dosage treatment, which lightened the patients’ economic burden while improving primary and long-term kidney function by promoting the recovery of graft function and decreasing hepatic and renal toxicity. The co-administration of diltiazem may also reduce the rate of acute rejection, especially in patients who also receive the triple immunosuppressive regimen consisting of CsA, mycophenolate mofetil, and Pred.

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Acknowledgments

This work was supported by the "13115" Innovation Technology Project of Special Purpose of Shanxi Province (2087ZDKG-67), the National Natural Science Foundation of China (30772096), the Natural Science Foundation of Shanxi Province ( 2007C2C12 ), the Project of the National Science Foundation for Distinguished Young Scholars of First Affiliated Hospital of the Medical College of Xi'an Jiaotong University (2006YK4), and the Science Research of Shanxi Health Department (08D25). We thank all doctors, nurses, and patients who took part in this study. This study was also supported by the Institute of Clinical Pharmacology, School of Xi’an Jiaotong University, the First Affiliated Hospital of Xi’an Jiaotong University. The Ethics Committee of the First Affiliated Hospital of Xi’an Jiaotong University approved the study. The authors declare that there are no competing interests.

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Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Third Affiliated Hospital (Shanxi Provincial People’s Hospital), Medical School of Xi’an Jiaotong University, Xi’an, Shanxi Province, China

    Yong Song

  2. Kidney Transplantation Department of Nephropathy Center, First Affiliated Hospital, Medical School of Xi’an Jiaotong University, Xi’an, Shanxi Province, China

    Wujun Xue, Puxun Tian, Xiaoming Ding, Xiaoming Pan, Hang Yan, Jun Hou, Xinshun Feng, Heli Xiang & Xiaohui Tian

  3. Department of Pediatrics, University of Alberta, Edmonton, AB, Canada

    Xiaohu Fan

  4. Department of Burn, Third Affiliated Hospital (Shanxi Provincial People’s Hospital), Medical School of Xi’an Jiaotong University, Xi’an, Shanxi Province, China

    Gaoping Qin

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  1. Yong Song
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Correspondence to Yong Song.

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Song, Y., Xue, W., Tian, P. et al. Combination therapy with diltiazem plus CsA/MMF/Pred or CsA/Aza/Pred triple immunosuppressive regimens for use in clinical kidney transplantation in Northwestern China. Eur J Clin Pharmacol 67, 553–562 (2011). https://doi.org/10.1007/s00228-011-0991-x

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