Infliximab Induction Lacks Efficacy and Increases BK Virus Infection in Deceased Donor Kidney Transplant Recipients

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

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Background: Ischemia-reperfusion (IR) of a kidney transplant (KTx) upregulates tumor necrosis factor alpha (TNF) production that amplifies allograft inflammation and may negatively impact transplant outcomes. Methods: We tested the effects of blocking TNF peri-KTx via a randomized, double-blind, placebo-controlled, 15-center, phase II clinical trial. Two-hundred twenty-five primary transplant recipients of deceased-donor kidneys (KTx) (38.2% Black/African-American, 44% White) were randomized to receive i.v. infliximab (IFX) 3 mg/kg or saline placebo (PLBO) initiated prior to \ kidney reperfusion. All subjects received rabbit anti-thymocyte globulin induction and maintenance immunosuppression (IS) with tacrolimus, mycophenolate mofetil, and prednisone. The primary endpoint was the difference between groups in mean 24-month estimated glomerular filtration rate (eGFR). Results: There was no difference in the primary endpoint, 24-mo eGFR between IFX (52.45 ml/min/1.73m 2, 95% CI 48.38-56.52) vs. PLBO (57.35 ml/min/1.73m 2, 95% CI 53.18-61.52, p=0.099). 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 ~10-fold lower TNF (p<0.001) in IFX vs. PLBO. BK viremia requiring IS change occurred more frequently in IFX (28.9%) vs. PLBO (13.4% p=0.004) with a strong trend toward higher rates of BKV nephropathy in IFX (13.3%) vs. 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 peri-transplant inflammation as a strategy to improve KTx outcomes.

Original languageEnglish (US)
JournalJournal of the American Society of Nephrology : JASN
StateE-pub ahead of print - Oct 4 2022
Externally publishedYes


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