The use of Everolimus as a part of maintenance immunosuppressive therapy in patients with minimal renal transplant dysfunction: results of a prospective observational program (CRAD001ARU01)
- Authors: Prokopenko E.I1, Stolyarevich E.S1
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Affiliations:
- Issue: No 1 (2017)
- Pages: 42-48
- Section: Articles
- URL: https://journals.eco-vector.com/2075-3594/article/view/272689
- ID: 272689
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Abstract
Aim. To evaluate the safety, tolerability and effectiveness of everolimus in adult renal transplant recipients with minimal manifestations of renal allograft (RAG) dysfunction and to assess the dynamics of the graft function. Material and methods. This prospective observational study comprised 45 adult patients (27 men and 18 women) from 9 Russian centers 4-60 months after renal transplantation with a low immunological risk and minimal graft dysfunction. Following enrollment in the study, the patient immunosuppression was converted from full-dose cyclosporine a (CsA), mycophenolate, and corticosteroids (CS) to everolimus, CS and the reduced dose of CSA. Twelve months follow-up included estimation of clinical and biochemical parameters, glomerular filtration rate (GFR), CO-blood concentration of CSA and everolimus, and registration of adverse events. results. All patients were alive at the end of the study. rag rejection rate was 6.7%. One patient lost the graft from severe rejection. The mean level of serum creatinine remained stable - 161.0±5.2 mmol/l at baseline and і60.5±8.6 mmol/l at 12 months, p=0,69. Baseline calculated GFR was 52.8±2.i ml/min, and 53.9±2.3 ml/min at 12 months, p=0.15. Mean CO-concentration of CSA significantly decreased from 79.0±5.6 ng/ml at day 4-5 after the everolimus administration to 49.0±4.5 ng/ml at 12 months, p<0.001. a significant reduction in systolic blood PRESSURE from 131.4±1.7 to 127.1±1.8 mmHg (P=0.01) was observed. Conclusion. Immunosuppression using everolimus concurrently with CS and reduced dose of CsA for 12 months was effective and safe in RAG recipients with low immunological risk. Apparently, such treatment may help inhibit chronic transplant nephropathy in the absence of rejection, but this has to be proven in further randomized trials.
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References
- Nankivell B.J.,Borrows R.J., Fung C.L., O’Connell P.J.,Allen R.D., Chapman J.R. The natural history of chronic allograft nephropathy. N. Engl. J. Med. 2003; 349: 2326-2333.
- Gaston R.S., Cecka J.M., Kasiske B.L., Fieberg A.M., Leduc R., Cosio F.C., Gourishankar S., Grande J., Halloran P., Hunsicker L., Mannon R., Rush D., Matas A.J. Evidence for antibody-mediated injury as a major determinant of late kidney allograft failure. Transplantation. 2010; 90(1): 68-74. doi: 10.1097/TP.0b013e3181e065de.
- Sawinski D., Trofe-Clark J., Leas B., Uhl S., Tuteja S., Kaczmarek J.L., French B., Umscheid C.A. Calcineurin Inhibitor minimization, conversion, withdrawal, and avoidance strategies in renal transplantation: a systematic review and metaanalysis. Am. J. Transplant. 2016; 16(7): 2117-2138. doi: 10.1111/ajt.13710.
- Vitko S., Tedesco H., Eris J., Pascual J., Whelchel J., Magee J.C., Campbell S., Civati G., Bourbigot B., Alves Filho G., Leone J., Garcia V.D., Rigotti P., Esmeraldo R., Cambi V., Haas T., Jappe A., Bernhardt P., Geissler J., Cretin N. Everolimus with optimized cyclosporine dosing in renal transplant recipients: 6-month safety and efficacy results of tow randomized studies. Am. J. Transplant. 2004; 4: 626-635.
- Chan L., Greenstein S., Hardy M.A., Hartmann E., Bunnapradist S., Cibrik D., Shaw L.M., Munir L., Ulbricht B., Cooper M.; CRADUS09 Study Group. Multicenter, randomized study of the use of everolimus with tacrolimus after renal transplantation demonstrates its effectiveness. Transplantation. 2008; 85: 821-826. doi: 10.1097/TP.0b013e318166927b.
- Tedesco Silva H. Jr., Cibrik D., Johnston T., Lackova E., Mange K., Panis C., Walker R., Wang Z., Zibari G., Kim Y.S. Everolimus plus reduced-exposure CsA versus mycophenolic acid plus standard exposure CsA in renal-transplant recipients. Am. J. Transplant. 2010; 10: 1401-1413. doi: 10.1111/j.16006143.2010.03129.x.
- Albano L., Berthoux F., Moal M.C., Rostaing L., Legendre C., Genin R., Toupance O., Moulin B., Merville P., Rerolle J.P., Bayle F., Westeei P.F., Glotz D., Kossari N., Lefrançois N., Charpentier B., Blanc A.S., Di Giambattista F., Dantal J.; RAD A2420 Study Group. Incidence of delayed graft function and wound healing complications after deceased-donor kidney transplantation is not affected by de novo everolimus. Transplantation. 2009; 88: 69-76. doi: 10.1097/TP.0b013e3181aa7d87.
- Holdaas H., Rostaing L., Seron D., Cole E., Chapman J., Fellstrom B., Strom E.H., Jardine A., Midtvedt K., Machein U., Ulbricht B., Karpov A., O’Connell P.J. ASCERTAIN Investigators. Conversion of long-term kidney transplant recipients from calcineurin inhibitor therapy to everolimus: a randomized, multicenter, 24-month study. Transplantation. 2011; 92: 410-418. Doi: 10.1097/ TP.0b013e318224c12d.
- Eisen H.J., Tuzcu E.M., Dorent R., Kobashigawa J., Mancini D., Valantine-von Kaeppler H.A., Starling R.C., Sorensen K., Hummel M., Lind J.M., Abeywickrama K.H., Bernhardt P.; RAD B253 Study Group. Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients. N. Engl. J. Med. 2003; 349: 847-858.
- Neale J., Smith A.C. Cardiovascular risk factors following renal transplant. World J. Transplant. 2015; 5(4): 183-195. doi: 10.5500/wjt.v5.i4.183.
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