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DOI: 10.1055/s-0034-1395686
Relationship between the Peripheral Lymphocyte Response to Mycophenolic Acid in vitro and the Level of ATP in Peripheral CD4+ Lymphocytes before and after Renal Transplantation
Publication History
received 23 June 2014
accepted 21 November 2014
Publication Date:
30 December 2014 (online)
![](https://www.thieme-connect.de/media/drugres/201512/lookinside/thumbnails/2014-06-0763_10-1055-s-0034-1395686-1.jpg)
Abstract
Objective: The lymphocyte immunosuppressant sensitivity test has been used to predict the pharmacodynamics of immunosuppressive drugs for the purpose of preventing acute rejection and infection after renal transplantation. On the other hand, measuring the ATP levels in peripheral CD4+ lymphocytes is also able to monitor the risks of rejection and infection in transplant recipients. In the present study, we examined the relationship between the mycophenolic acid pharmacodynamics and the ATP levels in peripheral lymphocytes before and after renal transplantation.
Methods: We examined both the pharmacological efficacy of mycophenolic acid and the lymphocyte ATP levels before and 2, 4 and 6 weeks after the operation in 20 renal transplant recipients. The drug’s pharmacological efficacy was evaluated by the 50% inhibitory concentration of the drug against the in vitro proliferation of peripheral blood lymphocytes activated by T cell mitogen. The ATP levels in peripheral CD4+ lymphocytes were measured by the Immuknow assay kit. The relationships between the mycophenolic acid pharmacodynamics and ATP levels in peripheral lymphocytes were examined in these recipients.
Results: The immunosupressive effects of mycophenolic acid against mitogen-activated lymphocyte proliferation were significantly and positively correlated with the lymphocyte ATP levels, but only at 6 weeks after transplantation. The relationship was not significant before or at 2 or 4 weeks after the operation.
Conclusion: Our present data raised the possibility that evaluating the pharmacological efficacy of mycophenolic acid pre-transplantation and monitoring the ATP level 6 weeks after transplantation can predict the risk of rejection and/or infection in renal transplant recipients.
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References
- 1 Sugiyama K, Isogai K, Horisawa S et al. Comparative study of the cellular pharmacodynamics of tacrolimus in renal transplant recipients treated with and without basiliximab. Cell Transplant 2012; 21: 565-570
- 2 Sugiyama K, Isogai K, Toyama A et al. Clinical significance of the pharmacological efficacy of tacrolimus estimated by the lymphocyte immunosuppressant sensitivity test (LIST) before and after renal transplantation. Cell Medicine 2012; 3: 81-88
- 3 Sugiyama K, Sasahara H, Tsukaguchi M et al. Peripheral lymphocyte-response to mycophenolic acid in vitro and incidence of cytomegalovirus infection in renal transplantation. Cell Medicine 2013; 6: 47-55
- 4 Sugiyama K, Tsukaguchi M, Toyama A et al. Clinical significance of immune monitoring by the lymphocyte ATP assay in renal transplant recipients. Exp Clin Transplant 2014; 3: 195-199
- 5 López-Hoyos M, Rodrigo E, Arias M. The usefulness of intracellular adenosine-5-triphosphate measurement in CD4+ cells in renal transplant. Nefrologia 2013; 33: 381-388
- 6 Kowalski R, Post D, Schneider MC et al. Immune cell function testing:an adjunct to therapeutic drug monitoring in transplant patient management. Clin Transplant 2003; 17: 77-88
- 7 Sánchez-Velasco P, Rodrigo E, Valero R et al. Intracellular ATP concentrations of CD4 cells in kidney transplant patients with and without infection. Clin Transplant 2008; 22: 55-60
- 8 Serban G, Whittaker V, Fan J et al. Significance of immune cell function monitoring in renal transplantation after Thymoglobulin induction therapy. Hum Immunol 2009; 70: 882-890
- 9 Zhou H, Lin J, Chen S et al. Use of the ImmuKnow assay to evaluate the effect of alemtuzumab-depleting induction therapy on cell-mediated immune function after renal transplantation. Clin Exp Nephrol 2013; 17: 304-309
- 10 Gralla J, Huskey J, Wiseman AC. Trends in immune function assay (ImmuKnow; Cylex™) results in the first year post-transplant and relationship to BK virus infection. Nephrol Dial Transplant 2012; 27: 2565-2570
- 11 Sugiyama K, Isogai K, Horisawa S et al. The pharmacological efficacy of mycophenolic acid before and after renal transplantation as estimated by the lymphocyte immunosuppressant sensitivity test (LIST). Immunopharmacol Immunotoxicol 2010; 32: 430-436
- 12 Sugiyama K, Isogai K, Toyama A et al. Correlation between the pharmacological efficacy of cyclosporine and tacrolimus as evaluated by the lymphocyte immunosuppressant sensitivity test (LIST) and the MTT assay procedure in patients before and after renal transplantation. Int J Clin Pharmacol Ther 2011; 49: 145-152
- 13 Sugiyama K, Isogai K, Toyama A et al. Cyclosporine pharmacological efficacy estimated by lymphocyte immunosuppressant sensitivity test before and after renal transplantation. J Clin Pharm Ther 2009; 34: 539-545
- 14 Sugiyama K, Satoh H, Saito K et al. Immunosuppressive efficacy of mycophenolate mofetil when compared with azathioprine and mizoribine against peripheral lymphocytes from renal transplant recipients. Transpl Int 2005; 18: 590-595
- 15 Hirano T, Oka K, Takeuchi H et al. Clinical significance of glucocorticoid pharmacodynamics assessed by antilymphocyte action in kidney transplantation. Marked difference between prednisolone and methylprednisolone. Transplantation. 1994; 57: 1341-1348
- 16 Sugiyama K, Isogai K, Toyama A et al. Pharmacodynamic parameters of immunosuppressive drugs are not correlated with age, duration of dialysis, percentage of lymphocytes or lymphocyte stimulation index in renal transplant recipients. Biol Pharm Bull 2008; 31: 2146-2149
- 17 Anthony CA. Approaches to the design of immunosuppressive agents. The Molecular Biology of Immunosuppression. John Wiley & Son Ltd; 1992: 181-209