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

22 Citations (Scopus)

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

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Mesenchymal Stromal Cells
Thoracic Surgery
Placebos
Recovery of Function
Kidney
Therapeutics
Mortality
North America
Dialysis
Creatinine
Confidence Intervals
Safety

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Swaminathan, M., Stafford-Smith, M., Chertow, G. M., Warnock, D. G., Paragamian, V., Brenner, R. M., ... 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
Swaminathan, Madhav ; Stafford-Smith, Mark ; Chertow, Glenn M. ; Warnock, David G. ; Paragamian, Viken ; Brenner, Robert M. ; Lellouche, François ; Fox-Robichaud, Alison ; Atta, Mohamed G. ; Melby, Spencer ; Mehta, Ravindra L. ; Wald, Ron ; Verma, Subodh ; Mazer, C. David ; Lombard, F. Willem ; Schroder, Jacob ; Kurtzberg, Joanne ; Bisnar, Tiffany ; Conte, John ; Dodd-O, Jeffrey ; Rabb, Hamid ; Katz, Nevin ; Shah, Ashish ; Huyette-Arrizza, Elizabeth ; Bellot, Chris ; Kramer, Robert ; Tolson, Betsey ; Solomon, Richard ; Brooks, Charles ; Mora-Mangano, Christina ; Wong, Jimmy ; Kashani, Kianoush ; Naka, Yoshifumi ; Umanath, Kausik ; Yee, Jerry ; Kilic, Ahmet ; Lecker, Stewart ; Frendl, Gyorgy ; MacKensen, Burkhard ; Simon, Mathieu ; Dagenais, Francois ; Ferland, Marie Claude ; Bouchard, Pierre Alexandre ; Whitlock, Richard ; Ainsworth, Craig ; McDonald, Ellen ; Curley, Gerard ; Yagnik, Sanjay ; Crescini, Charmagne ; Ferland, André ; Maier, Karen ; Denault, André ; Ly, Hung ; Bainbridge, Daniel ; Bentall, Tracey ; Légaré, Jean François ; Grocott, Hilary. / Allogeneic mesenchymal stem cells for treatment of AKI after cardiac surgery. In: Journal of the American Society of Nephrology. 2018 ; Vol. 29, No. 1. pp. 260-267.
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Swaminathan, M, Stafford-Smith, M, Chertow, GM, Warnock, DG, Paragamian, V, Brenner, RM, Lellouche, F, Fox-Robichaud, A, Atta, MG, Melby, S, Mehta, RL, Wald, R, Verma, S, Mazer, CD, Lombard, FW, Schroder, J, Kurtzberg, J, Bisnar, T, Conte, J, Dodd-O, J, Rabb, H, Katz, N, Shah, A, Huyette-Arrizza, E, Bellot, C, Kramer, R, Tolson, B, Solomon, R, Brooks, C, Mora-Mangano, C, Wong, J, Kashani, K, Naka, Y, Umanath, K, Yee, J, Kilic, A, Lecker, S, Frendl, G, MacKensen, B, Simon, M, Dagenais, F, Ferland, MC, Bouchard, PA, Whitlock, R, Ainsworth, C, McDonald, E, Curley, G, Yagnik, S, Crescini, C, Ferland, A, Maier, K, Denault, A, Ly, H, Bainbridge, D, Bentall, T, Légaré, JF & Grocott, H 2018, 'Allogeneic mesenchymal stem cells for treatment of AKI after cardiac surgery', Journal of the American Society of Nephrology, vol. 29, no. 1, pp. 260-267. https://doi.org/10.1681/ASN.2016101150

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

In: Journal of the American Society of Nephrology, Vol. 29, No. 1, 01.2018, p. 260-267.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Allogeneic mesenchymal stem cells for treatment of AKI after cardiac surgery

AU - Swaminathan, Madhav

AU - Stafford-Smith, Mark

AU - Chertow, Glenn M.

AU - Warnock, David G.

AU - Paragamian, Viken

AU - Brenner, Robert M.

AU - Lellouche, François

AU - Fox-Robichaud, Alison

AU - Atta, Mohamed G.

AU - Melby, Spencer

AU - Mehta, Ravindra L.

AU - Wald, Ron

AU - Verma, Subodh

AU - Mazer, C. David

AU - Lombard, F. Willem

AU - Schroder, Jacob

AU - Kurtzberg, Joanne

AU - Bisnar, Tiffany

AU - Conte, John

AU - Dodd-O, Jeffrey

AU - Rabb, Hamid

AU - Katz, Nevin

AU - Shah, Ashish

AU - Huyette-Arrizza, Elizabeth

AU - Bellot, Chris

AU - Kramer, Robert

AU - Tolson, Betsey

AU - Solomon, Richard

AU - Brooks, Charles

AU - Mora-Mangano, Christina

AU - Wong, Jimmy

AU - Kashani, Kianoush

AU - Naka, Yoshifumi

AU - Umanath, Kausik

AU - Yee, Jerry

AU - Kilic, Ahmet

AU - Lecker, Stewart

AU - Frendl, Gyorgy

AU - MacKensen, Burkhard

AU - Simon, Mathieu

AU - Dagenais, Francois

AU - Ferland, Marie Claude

AU - Bouchard, Pierre Alexandre

AU - Whitlock, Richard

AU - Ainsworth, Craig

AU - McDonald, Ellen

AU - Curley, Gerard

AU - Yagnik, Sanjay

AU - Crescini, Charmagne

AU - Ferland, André

AU - Maier, Karen

AU - Denault, André

AU - Ly, Hung

AU - Bainbridge, Daniel

AU - Bentall, Tracey

AU - Légaré, Jean François

AU - Grocott, Hilary

PY - 2018/1

Y1 - 2018/1

N2 - 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.

AB - 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.

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Swaminathan M, Stafford-Smith M, Chertow GM, Warnock DG, Paragamian V, Brenner RM et al. Allogeneic mesenchymal stem cells for treatment of AKI after cardiac surgery. Journal of the American Society of Nephrology. 2018 Jan;29(1):260-267. https://doi.org/10.1681/ASN.2016101150