Switching Calcineurin Inhibitors Medication in Renal Transplant Recipients to Belatacept Therapy: A systematic review.
Switching Calcineurin Inhibitors Medication in Renal Transplant Recipients to Belatacept Therapy: A systematic review.
Mohammad Amin Talebpour,1,*Minoo Momenzadeh,2Amir Hussein Bueik,3
1. Student Research Committee, Islamic Azad University, Mashhad branch, Mashhad, Iran. 2. School of Medicine , Mashhad Islamic Azad University, Mashhad , Iran 3. School of Medicine , Mashhad Islamic Azad University, Mashhad , Iran
Introduction: Background: Conversion to belatacept immunosuppression is a therapeutic option for renal-transplant recipients with calcineurin inhibitors (CNI) toxicity, but it associates with a high risk of acute rejection. Gradual conversion and serial immune monitoring with urinary chemokine CXCL9 may allow increasing the safety of this maneuver.
Methods: Methods & Search strategy: The Cochrane Library, PubMed/MEDLINE, EBSCO (Academic Search Ultimate), ProQuest (Central), and Excerpta Medical databases and Google Scholar were searched using the keywords (CNI AND Nephrotoxicity prevention) OR (“Calcineurin inhibitor” AND Nephrotoxicity) OR (Tacrolimus AND Nephrotoxicity) OR (Ciclosporin AND Nephrotoxicity) OR (cyclosporine AND Nephrotoxicity) OR (Belatacept) OR (CNI Conversion) for the period from 1990 to 2020. Fifty-five related articles and reviews were found. Finally, out of the total number of studies, 21 full texts were available, and using JBI's Checklist for Randomized Clinical trials Studies and JBI's Checklist for Cohort Studies, 17 studies passed the quality evaluation stage and entered the study. The statistical population in all studies monitored renal function, metabolic profile, and circulating lymphocyte subsets. Three also quantified urinary CXCL9 over a 12-month follow-up period.
Results: Result: Seventeen studies including 875 renal transplant recipients (346 belatacept converted) were analyzed in our study. All of the patients in the belatacept group were successfully switched to belatacept immunosuppression at 3.3 (1.3-7.2) years after transplant. Nineteen patients had a reversible rise in serum creatinine, associated with acute rejection in 6 cases. Urinary CXCL9 increased before serum creatinine. After conversion, blood pressure and HbA1c significantly declined while eGFR and proteinuria remained stable. The percentage of circulating effector T cells and memory B cells significantly declined.
Conclusion: Conclusion: A better understanding of the mechanisms underlying calcineurin inhibitor nephrotoxicity could help in the individualization of therapy for and prevention of CNI nephrotoxicity. Identification of high-risk patients for CNI nephrotoxicity before renal transplantation enables better use and selection of immunosuppression with reduced adverse effects and, eventually, successful treatment of the kidney recipients. Belatacept conversion is a good and safe option in patients with deteriorating renal function attributed to CNI nephrotoxicity.