FIRST EXPERIENCE IN SYSTEMIC ADMINISTRATION OF EVEROLIMUS IN RENAL TRANSPLANTATION FROM EXPANDED CRITERIA DONORS IN RUSSIAN FEDERATION

Author:

Uliyankina I. V.1,Skvortsov A. E.2,Ananiev A. N.2,Kutenkov A. A.1,Kuzmin D. O.1,Daineko V. S.1,Gogolev D. V.2,Reznik O. N.3

Affiliation:

1. Saint-Petersburg I.I. Dzhanelidze State Research Institute of Emergency Medicine

2. Pavlov First Saint Petersburg State Medical University

3. Saint-Petersburg I.I. Dzhanelidze State Research Institute of Emergency Medicine Pavlov First Saint Petersburg State Medical University

Abstract

Introduction. Kidney transplant (KTx) with reduced functional reserve is more sensitive to the toxic effects of calcineurin inhibitors (CNI). Immunosuppressive therapy (IST) approach with m-TOR inhibitors in case of KTx from expanded criteria donors (ECD) leads to decreasing levels of cyclosporine (CsA) in the blood. Despite the presence of international pilot studies we do not have yet clear recommendation as to combination of CsA and Everolimus. In this article, we presented 5-year results of the fi rst Russian experience of systematic administration of Everolimus as a basic IST in KTx from ECDs.Materials and methods.The group of recipients (n = 41) having received bilateral kidney transplants from the same ECDs was analyzed. Comparison group (n = 19) received standard IST consisting of CsA, MMF and steroids. Study group included 22 recipients who received kidneys from the same ECDs and IST based on early (starting from the 90th day after transplantation) conversion from MMF to Everolimus – 1.5 mg/day (target concentration – 3–6 ng/mL). Simultaneously with the administration of Everolimus, dosing of Neoral dropped immediately by 50%, and then, in accordance with the target concentration (C0 30–50 ng/mL). Dosage of steroids in patients of the study group was gradually minimized.Results.Both groups were comparable in terms of serum creatinine level and glomerular fi ltration rate (GFR) up to 3 months after transplantation. As a result of the introduction of a new IST scheme in the study group, serum creatinine level in 60 months after KTx was 149.27 ± 42.68 μmol/L, in the comparison group – 209.87 ± 39.56 μmol/L; р < 0.05. In the control group GFR reduced to 27.50 ± 7.39 mL/min/1.73 m2, in the study group it was 46.21 ± 15.17 mL/min/1.73 m2, p < 0.05.Conclusion.Early administration of Everolimus is strongly recommended in all cases of ECD KTx. This approach helps minimize CNI nephrotoxicity, provides the prevention of chronic allograft nephropathy, enables the stable renal function, and contributes to the survival of renal transplant recipients.

Publisher

V.I. Shimakov Federal Research Center of Transplantology and Artificial Organs

Subject

Transplantation,Immunology and Allergy

Reference52 articles.

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2. Naesens M, Kuypers DRJ, Sarwal M et al. Calcineurin Inhibitor Nephrotoxicity. Clin. J. Am. Soc. Nephrol. 2009 Feb; 4 (2): 481–508.

3. Chapman JR. Chronic Calcineurin Inhibitor Nephrotoxicity – Lest We Forget. Am. J. Transplant. 2011; 11 (4): 693–697.

4. Nankivell BJ, Wavamunno MD, Borrows RJ et al. Mycophenolate Mofetil Is Associated with Altered Expression of Chronic Renal Transplant Histology. Am. J. Transplant. 2007; 7 (2): 366–376.

5. Holdaas H, Midtvedt K, Asberget A. A drug safety evaluation of everolimus in kidney transplantation. Expert Opin. Drug. Saf. 2012; 11 (6): 1013–1022.

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