Allogeneic mesenchymal stem cells for treatment of AKI after cardiac surgery

Madhav Swaminathan, Mark Stafford-Smith, Glenn M. Chertow, David G. Warnock, Viken Paragamian, Robert M. Brenner, François Lellouche, Alison Fox-Robichaud, Mohamed G. Atta, Spencer Melby, Ravindra L. Mehta, Ron Wald, Subodh Verma, C. David Mazer, F. Willem Lombard, Jacob Schroder, Joanne Kurtzberg, Tiffany Bisnar, John Conte, Jeffrey Dodd-OHamid Rabb, Nevin Katz, Ashish Shah, Elizabeth Huyette-Arrizza, Chris Bellot, Robert Kramer, Betsey Tolson, Richard Solomon, Charles Brooks, Christina Mora-Mangano, Jimmy Wong, Kianoush Kashani, Yoshifumi Naka, Kausik Umanath, Jerry Yee, Ahmet Kilic, Stewart Lecker, Gyorgy Frendl, Burkhard MacKensen, Mathieu Simon, Francois Dagenais, Marie Claude Ferland, Pierre Alexandre Bouchard, Richard Whitlock, Craig Ainsworth, Ellen McDonald, Gerard Curley, Sanjay Yagnik, Charmagne Crescini, André Ferland, Karen Maier, André Denault, Hung Ly, Daniel Bainbridge, Tracey Bentall, Jean François Légaré, Hilary Grocott

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

AKI after cardiac surgery remains strongly associated with mortality and lacks effective treatment or prevention. Preclinical studies suggest that cell-based interventions may influence functional recovery. We conducted a phase 2, randomized, double-blind, placebo-controlled trial in 27 centers across North America to determine the safety and efficacy of allogeneic human mesenchymal stem cells (MSCs) in reducing the time to recovery from AKI after cardiac surgery. We randomized 156 adult subjects undergoing cardiac surgery with evidence of early AKI to receive intra-aortic MSCs (AC607; n=67) or placebo (n=68). The primary outcome was the time to recovery of kidney function defined as return of postintervention creatinine level to baseline. The median time to recovery of kidney function was 15 days with AC607 and 12 days with placebo (25th, 75th percentile range, 10-29 versus 6-21, respectively; hazard ratio, 0.81; 95% confidence interval, 0.53 to 1.24; P=0.32). We did not detect a significant difference between groups in 30-day all-cause mortality (16.7% with AC607; 11.8% with placebo) or dialysis (10.6% with AC607; 7.4% with placebo). At follow-up, 12 patients who received AC607 and six patients who received placebo had died. Rates of other adverse events did not differ between groups. In these patients with AKI after cardiac surgery, administration of allogeneic MSCs did not decrease the time to recovery of kidney function. Our results contrast with those in preclinical studies and provide important information regarding the potential effects of MSCs in this setting.

Original languageEnglish (US)
Pages (from-to)260-267
Number of pages8
JournalJournal of the American Society of Nephrology
Volume29
Issue number1
DOIs
StatePublished - Jan 2018

All Science Journal Classification (ASJC) codes

  • Nephrology

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    Swaminathan, M., Stafford-Smith, M., Chertow, G. M., Warnock, D. G., Paragamian, V., Brenner, R. M., Lellouche, F., Fox-Robichaud, A., Atta, M. G., Melby, S., Mehta, R. L., Wald, R., Verma, S., Mazer, C. D., Lombard, F. W., Schroder, J., Kurtzberg, J., Bisnar, T., Conte, J., ... Grocott, H. (2018). Allogeneic mesenchymal stem cells for treatment of AKI after cardiac surgery. Journal of the American Society of Nephrology, 29(1), 260-267. https://doi.org/10.1681/ASN.2016101150