Increased CMV disease and “severe” BK viremia with belatacept vs. sirolimus three-drug maintenance immunosuppression

• Published in: Transplant immunology Vol. 79; p. 101857
• Main Authors: Petrossian, Gregory, Ortiz, Jorge, Ortiz, Alejandro Chiodo, Addonizio, Kathryn, Hsiao, Alexander, James, Rosy, Koizumi, Naoru, Patel, Sunil, Plews, Robert
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2023
• Subjects: Abatacept - therapeutic use; Allergy and Immunology; Belatacept; BK polyomavirus; BK Virus; Cytomegalovirus; Cytomegalovirus Infections - drug therapy; Cytomegalovirus Infections - epidemiology; Delayed Graft Function - drug therapy; Graft Rejection - epidemiology; Humans; Immunosuppression Therapy; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; Kidney transplantation; Polyomavirus Infections - drug therapy; Polyomavirus Infections - epidemiology; Retrospective Studies; Sirolimus; Sirolimus - therapeutic use; Tacrolimus - therapeutic use; Viremia - drug therapy; Viremia - epidemiology; Cytomegalovirus; Belatacept; Sirolimus; BK polyomavirus; Kidney transplantation
• ISSN: 0966-3274; 1878-5492; 1878-5492
• DOI: 10.1016/j.trim.2023.101857

Belatacept may provide benefit in delayed graft function, but its association with infectious complications is understudied. We aim to assess the incidence of CMV and BK viremia in patients treated with sirolimus or belatacept as part of a three-drug immunosuppression regimen after kidney transplantation. Kidney transplant recipients from 01/01/2015 to 10/01/2021 were retrospectively reviewed. Maintenance immunosuppression was either tacrolimus, mycophenolate and sirolimus (B0) or tacrolimus, mycophenolate, and belatacept (5.0 mg/kg monthly) (B1). Primary outcomes of interest were BK and CMV viremia which were followed until the end of the study period. Secondary outcomes included graft function (serum creatinine, eGFR) and acute rejection through 12 months. Belatacept was initiated in patients with a higher mean kidney donor profile index (B0:0.36 vs. B1:0.44, p = .02) with more delayed graft function (B0:6.1% vs. B1:26.1%, p < .001). Belatacept therapy was associated with more “severe” CMV viremia >25,000 copies/mL (B0:1.2% vs. B1:5.9%, p = .016) and CMV disease (B0:0.41% vs. B1:4.2%, p = .015). However, there was no difference in the overall incidence of CMV viremia >200 IU/mL (B0:9.4% vs. B1:13.5%, p = .28). There was no difference in the incidence of BK viremia >200 IU/mL (B0:29.7% vs. B1:31.1%, p = .78) or BK-associated nephropathy (B0:2.4% vs. B1:1.7%, p = .58), but belatacept was associated with “severe” BK viremia, defined as >10,000 IU/mL (B0:13.0% vs. B1:21.8%, p = .03). The mean serum Cr was significantly higher with belatacept therapy at 1-year follow up (B0:1.24 mg/dL vs. B1:1.43 mg/dL, p = .003). Biopsy-proven acute rejection (B0:1.2% vs. B1:2.6%, p = .35) and graft loss (B0:1.2% vs. B1:0.84%, p = .81) were comparable at 12 months. Belatacept therapy was associated with an increased risk of CMV disease and “severe” CMV and BK viremia. However, this regimen did not increase the overall incidence of infection and facilitated comparable acute rejection and graft loss at 12-month follow up. •Novel belatacept-based regimen led to improvement in renal function through 12-months despite its use in suboptimal grafts.•Two unique, steroid-sparing immunosuppression regimens with impressively 12-month rejection rates <2%.•More severe CMV viremia with belatacept triple therapy suggests more aggressive surveillance is needed in these patients.