Skip to main content

Pretransplant assessment of cyclosporine level as a predictor of cyclosporine dose requirements after kidney transplantation

Abstract

Introduction and aims

Pretransplant administration of cyclosporine (CsA) may reduce post-transplant maintenance dose and consequently CsA inhibitor nephrotoxicity and helps in achieving the desired target C2 levels earlier. The optimum dose or timing of administration of CsA induction dose is still debatable.

Patients and methods

We compared three different protocols for pretransplant administration of CsA aiming to reach a target C2 therapeutic level of greater than 800 ng/ml on the third day post-transplant. Sixty kidney transplant recipients from Cairo University hospitals were divided into: group 1 (n=20) who received a single CsA induction dose of 2 mg/kg 12 h pretransplant; group 2 (n=20) who received four CsA consecutive doses of 4 mg/kg 48 h pre-transplant; and group 3 (n=20) who received four CsA consecutive doses of 2 mg/kg 48 h pretransplant.

Results

The desired therapeutic level in the earlier post-transplantation period was achieved in 65% in group 1, 100% in groups 2 and 3). In group 2 a lower dose was needed to maintain C2 within the therapeutic range during the first year post-transplantation (P<0.01). Furthermore, a lower number of cases were complicated by CsA nephrotoxicity in group 2 in comparison to groups 1 and 3 (25, 0, 5% in group 1, 2, 3, respectively, P<0.039). A higher longer dose of CsA pretransplant associated with early withdrawal of CsA had a better effect on graft function than lower or shorter induction doses with late withdrawal as evidenced by lower serum creatinine levels all through the follow-up period in group 2 compared with group 3.

Conclusion

Forty-eight-hour pretransplant induction with CsA at a dose of 4 mg/kg with early dose reduction post-transplant was associated with lower CsA maintenance and a better 1-year graft function.

References

  1. Muntean A, Lucan M. Immunosuppression in kidney transplantation. Clujul Med 2013; 86:177–180.

    PubMed  PubMed Central  Google Scholar 

  2. Ojo AO, Held PJ, Friedrich K, Port FK, Wolfe RA, Young EW, et al. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med 2003; 349:931–940.

    Article  CAS  Google Scholar 

  3. Issa N, Kukla A, Ibrahim HN. The over-exaggerated chronic nephrotoxicity of calcineurin inhibitors. Arab J Urol 2012; 10:169–174.

    Article  Google Scholar 

  4. Hamdy AF, Bakr MA, Ghoneim MA. Long-term efficacy and safety of a calcineurin inhibitor-free regimen in live-donor renal transplant recipients. J Am Soc Nephrol 2008; 19:1225–1232.

    Article  CAS  Google Scholar 

  5. Baraldo M, Risaliti A, Bresadola F, Chiarandini P, Dalla RG, Furlanut M. Circadian variations in cyclosporine C2 concentrations during the first 2 weeks after liver transplantation. Transplant Proc 2003; 35:1449–1451.

    Article  CAS  Google Scholar 

  6. Curtis JJ, Jones P, Barbeito R. Large within-day variation in cyclosporine absorption: circadian variation or food effect? Clin J Am Soc Nephrol 2006; 1:462–466.

    Article  CAS  Google Scholar 

  7. Mueller EA, Kovarik JM, van Bree JB, Grevel J, Lücker PW, Kutz K. Influence of a fat-rich meal on the pharmacokinetics of a new oral formulation of cyclosporine in a crossover comparison with the market formulation. Pharm Res 1994; 11:151–155.

    Article  CAS  Google Scholar 

  8. Sukhavasharin N, Praditpornsilpa K, Avihingsanon Y, Kuoatawintu P, O-Charoen R, Kansanabuch T, et al. Study of cyclosporine level at 2 h after administration in preoperative kidney transplant recipients for prediction of postoperative optimal cyclosporine dose. J Med Assoc Thai 2006; 89(Suppl 2):15–20.

    Google Scholar 

  9. Maamoun H, Soliman A, Zayed B. Cyclosporine and mycophenolate mofetil 48 h before renal transplantation enables the use of low cyclosporine doses and achieves better graft function. Transplant Proc 2010; 42:4033–4036.

    Article  CAS  Google Scholar 

  10. Klintmalm G, Sawe J, Ringden O, Von Bahr BC, Magnusson A. Cyclosporine plasma levels in renal transplant patients. Association with renal toxicity and allograft rejection. Transplantation 1985; 39:132–137.

    CAS  PubMed  Google Scholar 

  11. Fahr A. Cyclosporine clinical pharmacokinetics. Clin Pharmacokinet 1993; 24:472–495.

    Article  CAS  Google Scholar 

  12. Naesens M, Kuypers DR, Sarwal M. Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol 2009; 4:481–508.

    Article  CAS  Google Scholar 

  13. Henny FC, Kleinbloesem CH, Moolenaar AJ, Paul LC, Breimaer DD, van LA. Pharmacokinetics and nephrotoxicity of cyclosporine in renal transplant recipients. Transplantation 1985; 40:261–265.

    Article  CAS  Google Scholar 

  14. Ptachcinski RJ, Burckart GJ, Venkataramanan R. Cyclosporine concentration determinations for monitoring and pharmacokinetic studies. J Clin Pharmacol 1986; 26:358–366.

    Article  CAS  Google Scholar 

  15. Calne RY, White DJ, Thiru S, Evans DB, McMaster P, Dunn DC, et al. Cyclosporine A in patients receiving renal allografts from cadaver donors. Lancet 1978; 2:1323–1327.

    Article  CAS  Google Scholar 

  16. Calne RY, Rolles K, White DJ, et al. Cyclosporine A initially as the only immunosuppressant in 34 recipients of cadaveric organs: 32 kidneys, 2 pancreases, and 2 livers. Lancet 1979; 2:1033–1036.

    Article  CAS  Google Scholar 

  17. Cole E, Maham N, Cardella C, Cattran D, Fenton S, Hamel J et al. Clinical benefits of neoral C2 monitoring in the long-term management of renal transplant recipients. Transplantation 2003; 75:2086–2090.

    Article  Google Scholar 

  18. Naesens M, Kuypers DR, Sarwal M. Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol 2009; 4:481–508.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rabab M. Ahmed MD.

Additional information

This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

El-Khashab, S.O., Soliman, A.R., Ahmed, R.M. et al. Pretransplant assessment of cyclosporine level as a predictor of cyclosporine dose requirements after kidney transplantation. Egypt J Intern Med 31, 178–184 (2019). https://doi.org/10.4103/ejim.ejim_79_18

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.4103/ejim.ejim_79_18

Keywords