Efficacy of umbilical cord mesenchymal stem cell transfusion for the treatment of severe AKI: a protocol for a randomised controlled trial

Yuanjun Yang, Jianjun Gao, Siyang Wang, Wenjuan Wang, Fang-Lei Zhu, Xiaolong Wang, Shuang Liang, Zhe Feng, Shupeng Lin, Li Zhang, Xiangmei Chen, Guangyan Cai, Yuanjun Yang, Jianjun Gao, Siyang Wang, Wenjuan Wang, Fang-Lei Zhu, Xiaolong Wang, Shuang Liang, Zhe Feng, Shupeng Lin, Li Zhang, Xiangmei Chen, Guangyan Cai

Abstract

Introduction: Acute kidney injury (AKI) is a common and severe clinical problem that is associated with high mortality, a long hospital stays and high healthcare resource consumption. Approximately a quarter of AKI survivors will develop chronic kidney disease. Mesenchymal stem cells (MSCs) are multipotent stem cells with antiapoptotic, immunomodulatory, antioxidative and proangiogenic properties. Therefore, MSCs have been considered as a potential new therapy for the treatment of AKI. Several clinical trials have been performed, but the results have been inconsistent. This trial investigated whether MSCs can improve renal recovery and mortality in patients with severe AKI.

Methods and analysis: One hundred subjects suffering from severe AKI will participate in this patient-blinded, randomised, placebo-controlled, parallel design clinical trial. Participants will be randomly assigned to receive two doses of MSCs or placebo (saline) on days 0 and 7. Urinary biomarkers of renal injury and repair will be measured using commercially available ELISA kits. The main outcome measures are changes in renal function levels within the first 28 days following MSC infusion.

Ethics and dissemination: The study was approved by the Ethics Committee of the Chinese PLA General Hospital. The findings of the study will be disseminated through public and scientific channels.

Trial registration number: NCT04194671.

Keywords: acute renal failure; internal medicine; nephrology.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Flowchart of the efficacy of uc-MSC transfusion for patients with severe AKI. AKI, acute kidney injury; uc-MSC, umbilical cord mesenchymal stem cell.

References

    1. Yang X, de Caestecker M, Otterbein LE, et al. . Carbon monoxide: an emerging therapy for acute kidney injury. Med Res Rev 2020;40:1147-1177. 10.1002/med.21650
    1. Rewa O, Bagshaw SM. Acute kidney injury-epidemiology, outcomes and economics. Nat Rev Nephrol 2014;10:193–207. 10.1038/nrneph.2013.282
    1. Hoste EAJ, Kellum JA, Selby NM, et al. . Global epidemiology and outcomes of acute kidney injury. Nat Rev Nephrol 2018;14:607–25. 10.1038/s41581-018-0052-0
    1. Ishani A, Xue JL, Himmelfarb J, et al. . Acute kidney injury increases risk of ESRD among elderly. J Am Soc Nephrol 2009;20:223–8. 10.1681/ASN.2007080837
    1. Hoste EAJ, Bagshaw SM, Bellomo R, et al. . Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med 2015;41:1411–23. 10.1007/s00134-015-3934-7
    1. Kaddourah A, Basu RK, Bagshaw SM, et al. . Epidemiology of acute kidney injury in critically ill children and young adults. N Engl J Med 2017;376:11–20. 10.1056/NEJMoa1611391
    1. Thiele RH, Isbell JM, Rosner MH. AKI associated with cardiac surgery. Clin J Am Soc Nephrol 2015;10:500–14. 10.2215/CJN.07830814
    1. Rahman M, Shad F, Smith MC. Acute kidney injury: a guide to diagnosis and management. Am Fam Physician 2012;86:631–9.
    1. Chawla LS, Eggers PW, Star RA, et al. . Acute kidney injury and chronic kidney disease as interconnected syndromes. N Engl J Med 2014;371:58–66. 10.1056/NEJMra1214243
    1. Molitoris BA, Okusa MD, Palevsky PM, et al. . Design of clinical trials in AKI: a report from an NIDDK workshop. Trials of patients with sepsis and in selected Hospital settings. Clin J Am Soc Nephrol 2012;7:856–60. 10.2215/CJN.12821211
    1. Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney Int 2012;81:442–8. 10.1038/ki.2011.379
    1. Bonventre JV, Yang L. Cellular pathophysiology of ischemic acute kidney injury. J Clin Invest 2011;121:4210–21. 10.1172/JCI45161
    1. Lee K-H, Tseng W-C, Yang C-Y, et al. . The anti-inflammatory, anti-oxidative, and anti-apoptotic benefits of stem cells in acute ischemic kidney injury. Int J Mol Sci 2019;20. 10.3390/ijms20143529. [Epub ahead of print: 19 Jul 2019].
    1. Tammaro A, Kers J, Scantlebery AML, et al. . Metabolic flexibility and innate immunity in renal ischemia reperfusion injury: the fine balance between adaptive repair and tissue degeneration. Front Immunol 2020;11:1346. 10.3389/fimmu.2020.01346
    1. Gharaie Fathabad S, Kurzhagen JT, Sadasivam M, et al. . T lymphocytes in acute kidney injury and repair. Semin Nephrol 2020;40:114–25. 10.1016/j.semnephrol.2020.01.003
    1. Chen W, Li D. Reactive Oxygen Species (ROS)-Responsive Nanomedicine for Solving Ischemia-Reperfusion Injury. Front Chem 2020;8:732. 10.3389/fchem.2020.00732
    1. Shi Y, Wang Y, Li Q, et al. . Immunoregulatory mechanisms of mesenchymal stem and stromal cells in inflammatory diseases. Nat Rev Nephrol 2018;14:493–507. 10.1038/s41581-018-0023-5
    1. Özmert E, Arslan U. Management of retinitis pigmentosa by Wharton's jelly derived mesenchymal stem cells: preliminary clinical results. Stem Cell Res Ther 2020;11:25. 10.1186/s13287-020-1549-6
    1. Redondo J, Sarkar P, Kemp K, et al. . Dysregulation of mesenchymal stromal cell antioxidant responses in progressive multiple sclerosis. Stem Cells Transl Med 2018;7:748–58. 10.1002/sctm.18-0045
    1. Perico L, Morigi M, Rota C, et al. . Human mesenchymal stromal cells transplanted into mice stimulate renal tubular cells and enhance mitochondrial function. Nat Commun 2017;8:983. 10.1038/s41467-017-00937-2
    1. Chen H-H, Lin K-C, Wallace CG, et al. . Additional benefit of combined therapy with melatonin and apoptotic adipose-derived mesenchymal stem cell against sepsis-induced kidney injury. J Pineal Res 2014;57:16–32. 10.1111/jpi.12140
    1. Jiang MH, Li G, Liu J, et al. . Nestin(+) kidney resident mesenchymal stem cells for the treatment of acute kidney ischemia injury. Biomaterials 2015;50:56–66. 10.1016/j.biomaterials.2015.01.029
    1. Zhu G, Pei L, Lin F, et al. . Exosomes from human-bone-marrow-derived mesenchymal stem cells protect against renal ischemia/reperfusion injury via transferring miR-199a-3p. J Cell Physiol 2019;234:23736–49. 10.1002/jcp.28941
    1. Kim D-J, Moon J-Y, Kim S-M, et al. . Substance P improves renal ischemia reperfusion injury through modulating immune response. Front Immunol 2020;11:600. 10.3389/fimmu.2020.00600
    1. Cao H, Cheng Y, Gao H, et al. . In Vivo Tracking of Mesenchymal Stem Cell-Derived Extracellular Vesicles Improving Mitochondrial Function in Renal Ischemia-Reperfusion Injury. ACS Nano 2020;14:4014–26. 10.1021/acsnano.9b08207
    1. Westenfelder C, Togel FE. Protective actions of administered mesenchymal stem cells in acute kidney injury: relevance to clinical trials. Kidney Int Suppl 2011;1:103–6. 10.1038/kisup.2011.24
    1. Swaminathan M, Stafford-Smith M, Chertow GM, et al. . Allogeneic mesenchymal stem cells for treatment of AKI after cardiac surgery. J Am Soc Nephrol 2018;29:260–7. 10.1681/ASN.2016101150
    1. Tögel FE, Westenfelder C. Kidney protection and regeneration following acute injury: progress through stem cell therapy. Am J Kidney Dis 2012;60:1012–22. 10.1053/j.ajkd.2012.08.034
    1. Miller BLK, Garg P, Bronstein B, et al. . Extracorporeal stromal cell therapy for subjects with Dialysis-Dependent acute kidney injury. Kidney Int Rep 2018;3:1119–27. 10.1016/j.ekir.2018.05.009
    1. Robey TE, Saiget MK, Reinecke H, et al. . Systems approaches to preventing transplanted cell death in cardiac repair. J Mol Cell Cardiol 2008;45:567–81. 10.1016/j.yjmcc.2008.03.009
    1. Song H, Cha M-J, Song B-W, et al. . Reactive oxygen species inhibit adhesion of mesenchymal stem cells implanted into ischemic myocardium via interference of focal adhesion complex. Stem Cells 2010;28:555–63. 10.1002/stem.302
    1. Chang W, Song B-W, Moon J-Y, et al. . Anti-death strategies against oxidative stress in grafted mesenchymal stem cells. Histol Histopathol 2013;28:1529–36. 10.14670/HH-28.1529

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren