Intravenous Estrogen in Kidney Transplant Study

Summary

Ischemia perfusion injury (IRI) is a major cause of organ injury during kidney transplantation. Currently there are no treatments for IRI other than dialysis. Preliminary studies in female mice have found protection from IRI when given short term estrogen supplements. This study will look at the effect of intravenous estrogen given peri-operatively to reduce the effect of IRI in female kidney transplant recipients.

Timeline

Start

2016-08-26

Primary completion

2027-01-31

Completion

2027-05-01

Publications

• Background Siedlecki A, Irish W, Brennan DC. Delayed graft function in the kidney transplant. Am J Transplant. 2011 Nov;11(11):2279-96. doi: 10.1111/j.1600-6143.2011.03754.x. Epub 2011 Sep 19.
• Background Kher A, Meldrum KK, Wang M, Tsai BM, Pitcher JM, Meldrum DR. Cellular and molecular mechanisms of sex differences in renal ischemia-reperfusion injury. Cardiovasc Res. 2005 Sep 1;67(4):594-603. doi: 10.1016/j.cardiores.2005.05.005.
• Background Kher A, Wang M, Tsai BM, Pitcher JM, Greenbaum ES, Nagy RD, Patel KM, Wairiuko GM, Markel TA, Meldrum DR. Sex differences in the myocardial inflammatory response to acute injury. Shock. 2005 Jan;23(1):1-10. doi: 10.1097/01.shk.0000148055.12387.15.
• Background Hedges SJ, Dehoney SB, Hooper JS, Amanzadeh J, Busti AJ. Evidence-based treatment recommendations for uremic bleeding. Nat Clin Pract Nephrol. 2007 Mar;3(3):138-53. doi: 10.1038/ncpneph0421.
• Background Wigginton JG, Pepe PE, Idris AH. Rationale for routine and immediate administration of intravenous estrogen for all critically ill and injured patients. Crit Care Med. 2010 Oct;38(10 Suppl):S620-9. doi: 10.1097/CCM.0b013e3181f243a9.
• Background Bradley LD, Gueye NA. The medical management of abnormal uterine bleeding in reproductive-aged women. Am J Obstet Gynecol. 2016 Jan;214(1):31-44. doi: 10.1016/j.ajog.2015.07.044. Epub 2015 Aug 5.
• Background Murray AW, Barnfield MC, Waller ML, Telford T, Peters AM. Assessment of glomerular filtration rate measurement with plasma sampling: a technical review. J Nucl Med Technol. 2013 Jun;41(2):67-75. doi: 10.2967/jnmt.113.121004. Epub 2013 May 8.
• Results Ojo AO, Wolfe RA, Held PJ, Port FK, Schmouder RL. Delayed graft function: risk factors and implications for renal allograft survival. Transplantation. 1997 Apr 15;63(7):968-74. doi: 10.1097/00007890-199704150-00011.
• Results Alves MG, Oliveira PJ, Carvalho RA. Substrate selection in hearts subjected to ischemia/reperfusion: role of cardioplegic solutions and gender. NMR Biomed. 2011 Nov;24(9):1029-37. doi: 10.1002/nbm.1640. Epub 2011 Jan 28.
• Results Ardelt AA, Carpenter RS, Lobo MR, Zeng H, Solanki RB, Zhang A, Kulesza P, Pike MM. Estradiol modulates post-ischemic cerebral vascular remodeling and improves long-term functional outcome in a rat model of stroke. Brain Res. 2012 Jun 21;1461:76-86. doi: 10.1016/j.brainres.2012.04.024. Epub 2012 Apr 21.
• Results Eckhoff DE, Bilbao G, Frenette L, Thompson JA, Contreras JL. 17-Beta-estradiol protects the liver against warm ischemia/reperfusion injury and is associated with increased serum nitric oxide and decreased tumor necrosis factor-alpha. Surgery. 2002 Aug;132(2):302-9. doi: 10.1067/msy.2002.125718.
• Results Gabel SA, Walker VR, London RE, Steenbergen C, Korach KS, Murphy E. Estrogen receptor beta mediates gender differences in ischemia/reperfusion injury. J Mol Cell Cardiol. 2005 Feb;38(2):289-97. doi: 10.1016/j.yjmcc.2004.11.013. Epub 2005 Jan 20.
• Results Peng X, Wang J, Lassance-Soares RM, Najafi AH, Sood S, Aghili N, Alderman LO, Panza JA, Faber JE, Wang S, Epstein SE, Burnett MS. Gender differences affect blood flow recovery in a mouse model of hindlimb ischemia. Am J Physiol Heart Circ Physiol. 2011 Jun;300(6):H2027-34. doi: 10.1152/ajpheart.00004.2011. Epub 2011 Mar 11.
• Results Hu H, Wang G, Batteux F, Nicco C. Gender differences in the susceptibility to renal ischemia-reperfusion injury in BALB/c mice. Tohoku J Exp Med. 2009 Aug;218(4):325-9. doi: 10.1620/tjem.218.325.
• Results Muller V, Szabo A, Viklicky O, Gaul I, Portl S, Philipp T, Heemann UW. Sex hormones and gender-related differences: their influence on chronic renal allograft rejection. Kidney Int. 1999 May;55(5):2011-20. doi: 10.1046/j.1523-1755.1999.00441.x.
• Results Muller V, Losonczy G, Heemann U, Vannay A, Fekete A, Reusz G, Tulassay T, Szabo AJ. Sexual dimorphism in renal ischemia-reperfusion injury in rats: possible role of endothelin. Kidney Int. 2002 Oct;62(4):1364-71. doi: 10.1111/j.1523-1755.2002.kid590.x.
• Results Park KM, Kim JI, Ahn Y, Bonventre AJ, Bonventre JV. Testosterone is responsible for enhanced susceptibility of males to ischemic renal injury. J Biol Chem. 2004 Dec 10;279(50):52282-92. doi: 10.1074/jbc.M407629200. Epub 2004 Sep 8.
• Results Park KM, Cho HJ, Bonventre JV. Orchiectomy reduces susceptibility to renal ischemic injury: a role for heat shock proteins. Biochem Biophys Res Commun. 2005 Mar 4;328(1):312-7. doi: 10.1016/j.bbrc.2004.12.177.
• Results Robert R, Ghazali DA, Favreau F, Mauco G, Hauet T, Goujon JM. Gender difference and sex hormone production in rodent renal ischemia reperfusion injury and repair. J Inflamm (Lond). 2011 Jun 9;8:14. doi: 10.1186/1476-9255-8-14.
• Results Rusai K, Prokai A, Szebeni B, Meszaros K, Fekete A, Szalay B, Vannay A, Degrell P, Muller V, Tulassay T, Szabo AJ. Gender differences in serum and glucocorticoid regulated kinase-1 (SGK-1) expression during renal ischemia/reperfusion injury. Cell Physiol Biochem. 2011;27(6):727-38. doi: 10.1159/000330081. Epub 2011 Jun 17.
• Results Shen SQ, Zhang Y, Xiong CL. The protective effects of 17beta-estradiol on hepatic ischemia-reperfusion injury in rat model, associated with regulation of heat-shock protein expression. J Surg Res. 2007 Jun 1;140(1):67-76. doi: 10.1016/j.jss.2006.10.022. Epub 2007 Mar 2.
• Results Soljancic A, Ruiz AL, Chandrashekar K, Maranon R, Liu R, Reckelhoff JF, Juncos LA. Protective role of testosterone in ischemia-reperfusion-induced acute kidney injury. Am J Physiol Regul Integr Comp Physiol. 2013 Jun 1;304(11):R951-8. doi: 10.1152/ajpregu.00360.2012. Epub 2013 Apr 3.
• Results Wittnich C, Belanger MP, Askin N, Boscarino C, Wallen WJ. Lower liver transplant success in females: gender differences in metabolic response to global ischemia. Transplant Proc. 2004 Jun;36(5):1485-8. doi: 10.1016/j.transproceed.2004.05.055.
• Results Antus B, Liu S, Yao Y, Zou H, Song E, Lutz J, Heemann U. Effects of progesterone and selective oestrogen receptor modulators on chronic allograft nephropathy in rats. Nephrol Dial Transplant. 2005 Feb;20(2):329-35. doi: 10.1093/ndt/gfh602. Epub 2004 Dec 23.
• Results Antus B, Yao Y, Song E, Liu S, Lutz J, Heemann U. Opposite effects of testosterone and estrogens on chronic allograft nephropathy. Transpl Int. 2002 Oct;15(9-10):494-501. doi: 10.1007/s00147-002-0449-2. Epub 2002 Sep 20.
• Results Aufhauser DD Jr, Wang Z, Murken DR, Bhatti TR, Wang Y, Ge G, Redfield RR 3rd, Abt PL, Wang L, Svoronos N, Thomasson A, Reese PP, Hancock WW, Levine MH. Improved renal ischemia tolerance in females influences kidney transplantation outcomes. J Clin Invest. 2016 May 2;126(5):1968-77. doi: 10.1172/JCI84712. Epub 2016 Apr 18.
• Results Livio M, Mannucci PM, Vigano G, Mingardi G, Lombardi R, Mecca G, Remuzzi G. Conjugated estrogens for the management of bleeding associated with renal failure. N Engl J Med. 1986 Sep 18;315(12):731-5. doi: 10.1056/NEJM198609183151204.
• Results Heistinger M, Stockenhuber F, Schneider B, Pabinger I, Brenner B, Wagner B, Balcke P, Lechner K, Kyrle PA. Effect of conjugated estrogens on platelet function and prostacyclin generation in CRF. Kidney Int. 1990 Dec;38(6):1181-6. doi: 10.1038/ki.1990.331.
• Results Vigano G, Gaspari F, Locatelli M, Pusineri F, Bonati M, Remuzzi G. Dose-effect and pharmacokinetics of estrogens given to correct bleeding time in uremia. Kidney Int. 1988 Dec;34(6):853-8. doi: 10.1038/ki.1988.260.
• Results DeVore GR, Owens O, Kase N. Use of intravenous Premarin in the treatment of dysfunctional uterine bleeding--a double-blind randomized control study. Obstet Gynecol. 1982 Mar;59(3):285-91.

Drugs

Indications