Safety and Tolerability Study of an Intravenously Administered Small Interfering Ribonucleic Acid (siRNA) Post On-Pump Cardiothoracic Surgery in Patients at Risk of Acute Kidney Injury

Kidney International Reports

Volumn 2, Issue 5, 2017, Pages 836-843

  Demirjian, Segav ^a   Ailawadi, Gorav ^b   Polinsky, Martin ^c   Bitran, Dani ^d   Silberman, Shuli ^d   Shernan, Stanton Keith ^e   Burnier, Michel ^f   Hamilton, Marta ^g   Squiers, Elizabeth ^c   Erlich, Shai ^c   Rothenstein, Daniel ^c   Khan, Samina ^c   Chawla, Lakhmir S ^h  

^a LERNER RESEARCH INSTITUTE   (United States)

^b UNIVERSITY OF VIRGINIA   (United States)

^c QBI Enterprises Ltd   (Israel)

^d SHAARE ZEDEK MEDICAL CENTER   (Israel)

^e BRIGHAM AND WOMEN S HOSPITAL   (United States)

^f LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

^g Hamilton Consulting Group LLC   (United States)

^h VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

acute kidney injury; cardiopulmonary bypass; clinical trial; oligonucleotide; pharmacokinetics; siRNA

Indexed keywords

EID: 85030153026     PISSN: 24680249     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ekir.2017.03.016     Document Type: Article

References (20)

1. Chertow, G.M., Burdick, E., Honour, M., et al. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol 16 (2005), 3365–3370.
2. Chawla, L., Amdur, R., Shaw, A., et al. Association between AKI and long-term renal and cardiovascular outcomes in United States veterans. Clin J Am Soc Nephrol 9 (2014), 448–456.
3. Hobson, C.E., Yavas, S., Segal, M.S., et al. Acute kidney injury is associated with increased long-term mortality after cardiothoracic surgery. Circulation 119 (2009), 2444–2453.
4. Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2 (2012), 1–138.
5. Molitoris, B.A., Dagher, P.C., Sandoval, R.M., et al. siRNA targeted to p53 attenuates ischemic and cisplatin-induced acute kidney injury. J Am Soc Nephrol 20 (2009), 1754–1764.
6. Komarov, P.G., Komarova, E.A., Kondratov, R.V., et al. A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science 285 (1999), 1733–1737.
7. Fitzgerald, K., Frank-Kamenetsky, M., Shulga-Morskaya, S., et al. Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomized single-blind placebo-controlled phase 1 trial. Lancet 383 (2014), 60–68.
8. Kelly, K.J., Plotkin, Z., Vulgamott, S.L., et al. P53 mediates the apoptotic response to GTP depletion after renal ischemia-reperfusion: protective role of a p53 inhibitor. J Am Soc Nephrol 14 (2003), 128–138.
9. Thakar, C.V., Arrigain, S., Worley, S., et al. A clinical score to predict acute renal failure after cardiac surgery. J Am Soc Nephrol 16 (2005), 162–168.
10. Naito, A.T., Okada, S., Minamino, T., et al. Promotion of CHIP-mediated p53 degradation protects the heart from ischemic injury. Circ Res 106 (2010), 1692–1702.
11. Nijboer, C.H., Heijnen, C.J., van der Kooij, M.A., et al. Targeting the p53 pathway to protect the neonatal ischemic brain. Ann Neurol 70 (2011), 255–264.
12. Singaravelu, K., Padanilam, B.J., p53 target Siva regulates apoptosis in ischemic kidneys. Am J Physiol Renal Physiol, 300, 2011, F1130.
13. Hoshino, A., Matoba, S., Iwai-Kanai, E., et al. p53-TIGAR axis attenuates mitophagy to exacerbate cardiac damage after ischemia. J Mol Cell Cardiol 52 (2012), 175–184.
14. Vaseva, A.V., Marchenko, N.D., Ji, K., et al. p53 opens the mitochondrial permeability transition pore to trigger necrosis. Cell 149 (2012), 1536–1548.
15. Fire, A., Xu, S., Montgomery, M.K., et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391 (1998), 806–811.
16. Sutton, T.A., Hato, T., Mai, E., et al. p53 is renoprotective after ischemic kidney injury by reducing inflammation. J Am Soc Nephrol, 24, 2012, 113.
17. Wei, Q., Dong, G., Yang, T., et al. Activation and involvement of p53 in cisplatin-induced nephrotoxicity. Am J Physiol Renal Physiol 293 (2007), F1282–F1291.
18. Mulay, S.R., Thomasova, D., Ryu, M., et al. MDM2 (murine double minute-2) links inflammation and tubular cell healing during acute kidney injury in mice. Kidney Int 81 (2012), 1199–1211.
19. Christophorou, M.A., Ringshausen, I., Finch, A.J., et al. The pathological response to DNA damage does not contribute to p53-mediated tumour suppression. Nature 443 (2006), 214–217.
20. Henry, S.P., Monteith, D., Levin, A.A., Effects of intravenous infusion of phosphorothioate oligonucleotides on coagulation, complement activation and hemodynamics. Nucleosides Nucleotides 16 (1997), 1673–1676.