Infliximab Induction Lacks Efficacy and Increases BK Virus Infection in Deceased Donor Kidney Transplant Recipients: Results of the CTOT-19 Trial

Donald E. Hricik, Brian Armstrong, Tarek Alhamad, Daniel C. Brennan, Jonathan S. Bromberg, Suphamai Bunnapradist, Sindhu Chandran, Robert L. Fairchild, David P. Foley, Richard Formica, Ian W. Gibson, Karen Kesler, S. Joseph Kim, Roslyn B. Mannon, Madhav C. Menon, Kenneth A. Newell, Peter Nickerson, Jonah Odim, Emilio D. Poggio, Randall SungRon Shapiro, Kathryn Tinckam, Flavio Vincenti, Peter S. Heeger

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Ischemia-reperfusion (IR) of a kidney transplant (KTx) upregulates TNF α production that amplifies allograft inflammation and may negatively affect transplant outcomes. METHODS: We tested the effects of blocking TNF peri-KTx via a randomized, double-blind, placebo-controlled, 15-center, phase 2 clinical trial. A total of 225 primary transplant recipients of deceased-donor kidneys (KTx; 38.2% Black/African American, 44% White) were randomized to receive intravenous infliximab (IFX) 3 mg/kg or saline placebo (PLBO) initiated before kidney reperfusion. All patients received rabbit anti-thymocyte globulin induction and maintenance immunosuppression (IS) with tacrolimus, mycophenolate mofetil, and prednisone. The primary end point was the difference between groups in mean 24-month eGFR. RESULTS: There was no difference in the primary end point of 24-month eGFR between IFX (52.45 ml/min per 1.73 m 2 ; 95% CI, 48.38 to 56.52) versus PLBO (57.35 ml/min per 1.73 m 2 ; 95% CI, 53.18 to 61.52; P =0.1). There were no significant differences between groups in rates of delayed graft function, biopsy-proven acute rejection (BPAR), development of de novo donor-specific antibodies, or graft loss/death. Immunosuppression did not differ, and day 7 post-KTx plasma analyses showed approximately ten-fold lower TNF ( P <0.001) in IFX versus PLBO. BK viremia requiring IS change occurred more frequently in IFX (28.9%) versus PLBO (13.4%; P =0.004), with a strong trend toward higher rates of BKV nephropathy in IFX (13.3%) versus PLBO (4.9%; P =0.06). CONCLUSIONS: IFX induction therapy does not benefit recipients of kidney transplants from deceased donors on this IS regimen. Because the intervention unexpectedly increased rates of BK virus infections, our findings underscore the complexities of targeting peritransplant inflammation as a strategy to improve KTx outcomes.Clinical Trial registry name and registration (NCT02495077).

Original languageEnglish
Pages (from-to)145-159
Number of pages15
JournalJournal of the American Society of Nephrology : JASN
Issue number1
StatePublished - Jan 1 2023


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