Preventing Acute Kidney Injury (AKI) in Pediatric Patients

Summary

The purpose of this study is to compare the effects of peri-operative administration of Aminophylline versus Saline placebo in the preservation of renal function and the attenuation of renal injury in pediatric patients undergoing open heart surgery.

Timeline

Start

2019-02-07

Primary completion

2023-02-01

Completion

2024-02-01

Publications

• Background 1.KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int. Suppl 2 ; 2012:1-138
• Background Bojan M, Gioanni S, Vouhe PR, Journois D, Pouard P. Early initiation of peritoneal dialysis in neonates and infants with acute kidney injury following cardiac surgery is associated with a significant decrease in mortality. Kidney Int. 2012 Aug;82(4):474-81. doi: 10.1038/ki.2012.172.
• Background 11.Gouyon JB, Guignard JP. Glomerular filtration rates in neonates. In Oh w, Guignard JP, Baumgart S (Eds.): Nephrology and Fluid / Electrolyte Physiology, First edn (pp 79-96). Philadelphia: Saunders Elsevier 2008
• Background Linden J and Jacobson KA. Molecular biology and pharmacology of adenosine receptors. Cardiovascular Biology of Purines, 1-20 (Eds Burnstock G et al.) Dordrecht: Kluwer Academic Publishers.
• Results Rigden SP, Barratt TM, Dillon MJ, De Leval M, Stark J. Acute renal failure complicating cardiopulmonary bypass surgery. Arch Dis Child. 1982 Jun;57(6):425-30. doi: 10.1136/adc.57.6.425.
• Results Sorof JM, Stromberg D, Brewer ED, Feltes TF, Fraser CD Jr. Early initiation of peritoneal dialysis after surgical repair of congenital heart disease. Pediatr Nephrol. 1999 Oct;13(8):641-5. doi: 10.1007/s004670050672.
• Results Chan KL, Ip P, Chiu CS, Cheung YF. Peritoneal dialysis after surgery for congenital heart disease in infants and young children. Ann Thorac Surg. 2003 Nov;76(5):1443-9. doi: 10.1016/s0003-4975(03)01026-9.
• Results Boigner H, Brannath W, Hermon M, Stoll E, Burda G, Trittenwein G, Golej J. Predictors of mortality at initiation of peritoneal dialysis in children after cardiac surgery. Ann Thorac Surg. 2004 Jan;77(1):61-5. doi: 10.1016/s0003-4975(03)01490-5.
• Results Pedersen KR, Povlsen JV, Christensen S, Pedersen J, Hjortholm K, Larsen SH, Hjortdal VE. Risk factors for acute renal failure requiring dialysis after surgery for congenital heart disease in children. Acta Anaesthesiol Scand. 2007 Nov;51(10):1344-9. doi: 10.1111/j.1399-6576.2007.01379.x.
• Results Pedersen KR, Hjortdal VE, Christensen S, Pedersen J, Hjortholm K, Larsen SH, Povlsen JV. Clinical outcome in children with acute renal failure treated with peritoneal dialysis after surgery for congenital heart disease. Kidney Int Suppl. 2008 Apr;(108):S81-6. doi: 10.1038/sj.ki.5002607.
• Results Ronco C, Haapio M, House AA, Anavekar N, Bellomo R. Cardiorenal syndrome. J Am Coll Cardiol. 2008 Nov 4;52(19):1527-39. doi: 10.1016/j.jacc.2008.07.051.
• Results Blinder JJ, Goldstein SL, Lee VV, Baycroft A, Fraser CD, Nelson D, Jefferies JL. Congenital heart surgery in infants: effects of acute kidney injury on outcomes. J Thorac Cardiovasc Surg. 2012 Feb;143(2):368-74. doi: 10.1016/j.jtcvs.2011.06.021. Epub 2011 Jul 27.
• Results Gouyon JB, Guignard JP. Functional renal insufficiency: role of adenosine. Biol Neonate. 1988;53(4):237-42. doi: 10.1159/000242796.
• Results Hall JE, Granger JP, Hester RL. Interactions between adenosine and angiotensin II in controlling glomerular filtration. Am J Physiol. 1985 Mar;248(3 Pt 2):F340-6. doi: 10.1152/ajprenal.1985.248.3.F340.
• Results Hansen PB, Schnermann J. Vasoconstrictor and vasodilator effects of adenosine in the kidney. Am J Physiol Renal Physiol. 2003 Oct;285(4):F590-9. doi: 10.1152/ajprenal.00051.2003.
• Results Rabb H. The promise of immune cell therapy for acute kidney injury. J Clin Invest. 2012 Nov;122(11):3852-4. doi: 10.1172/JCI66455. Epub 2012 Oct 24.
• Results Fredholm BB, IJzerman AP, Jacobson KA, Klotz KN, Linden J. International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev. 2001 Dec;53(4):527-52.
• Results Pawelczyk T, Grden M, Rzepko R, Sakowicz M, Szutowicz A. Region-specific alterations of adenosine receptors expression level in kidney of diabetic rat. Am J Pathol. 2005 Aug;167(2):315-25. doi: 10.1016/S0002-9440(10)62977-X.
• Results Navar LG, Inscho EW, Majid SA, Imig JD, Harrison-Bernard LM, Mitchell KD. Paracrine regulation of the renal microcirculation. Physiol Rev. 1996 Apr;76(2):425-536. doi: 10.1152/physrev.1996.76.2.425.
• Results Vitzthum H, Weiss B, Bachleitner W, Kramer BK, Kurtz A. Gene expression of adenosine receptors along the nephron. Kidney Int. 2004 Apr;65(4):1180-90. doi: 10.1111/j.1523-1755.2004.00490.x.
• Results Silldorff EP, Pallone TL. Adenosine signaling in outer medullary descending vasa recta. Am J Physiol Regul Integr Comp Physiol. 2001 Mar;280(3):R854-61. doi: 10.1152/ajpregu.2001.280.3.R854.
• Results Nishiyama A, Inscho EW, Navar LG. Interactions of adenosine A1 and A2a receptors on renal microvascular reactivity. Am J Physiol Renal Physiol. 2001 Mar;280(3):F406-14. doi: 10.1152/ajprenal.2001.280.3.F406.
• Results Okusa MD, Linden J, Macdonald T, Huang L. Selective A2A adenosine receptor activation reduces ischemia-reperfusion injury in rat kidney. Am J Physiol. 1999 Sep;277(3):F404-12. doi: 10.1152/ajprenal.1999.277.3.F404.
• Results Lee HT, Emala CW. Systemic adenosine given after ischemia protects renal function via A(2a) adenosine receptor activation. Am J Kidney Dis. 2001 Sep;38(3):610-8. doi: 10.1053/ajkd.2001.26888.
• Results Okusa MD, Linden J, Huang L, Rosin DL, Smith DF, Sullivan G. Enhanced protection from renal ischemia-reperfusion [correction of ischemia:reperfusion] injury with A(2A)-adenosine receptor activation and PDE 4 inhibition. Kidney Int. 2001 Jun;59(6):2114-25. doi: 10.1046/j.1523-1755.2001.00726.x.
• Results Reece TB, Davis JD, Okonkwo DO, Maxey TS, Ellman PI, Li X, Linden J, Tribble CG, Kron IL, Kern JA. Adenosine A2A analogue reduces long-term neurologic injury after blunt spinal trauma. J Surg Res. 2004 Sep;121(1):130-4. doi: 10.1016/j.jss.2004.04.006.
• Results Ross SD, Tribble CG, Linden J, Gangemi JJ, Lanpher BC, Wang AY, Kron IL. Selective adenosine-A2A activation reduces lung reperfusion injury following transplantation. J Heart Lung Transplant. 1999 Oct;18(10):994-1002. doi: 10.1016/s1053-2498(99)00066-2.
• Results Odashima M, Bamias G, Rivera-Nieves J, Linden J, Nast CC, Moskaluk CA, Marini M, Sugawara K, Kozaiwa K, Otaka M, Watanabe S, Cominelli F. Activation of A2A adenosine receptor attenuates intestinal inflammation in animal models of inflammatory bowel disease. Gastroenterology. 2005 Jul;129(1):26-33. doi: 10.1053/j.gastro.2005.05.032.
• Results Glover DK, Riou LM, Ruiz M, Sullivan GW, Linden J, Rieger JM, Macdonald TL, Watson DD, Beller GA. Reduction of infarct size and postischemic inflammation from ATL-146e, a highly selective adenosine A2A receptor agonist, in reperfused canine myocardium. Am J Physiol Heart Circ Physiol. 2005 Apr;288(4):H1851-8. doi: 10.1152/ajpheart.00362.2004. Epub 2004 Dec 9.
• Results Day YJ, Huang L, Ye H, Li L, Linden J, Okusa MD. Renal ischemia-reperfusion injury and adenosine 2A receptor-mediated tissue protection: the role of CD4+ T cells and IFN-gamma. J Immunol. 2006 Mar 1;176(5):3108-14. doi: 10.4049/jimmunol.176.5.3108.
• Results Vallon V, Muhlbauer B, Osswald H. Adenosine and kidney function. Physiol Rev. 2006 Jul;86(3):901-40. doi: 10.1152/physrev.00031.2005.
• Results Gouyon JB, Guignard JP. Theophylline prevents the hypoxemia-induced renal hemodynamic changes in rabbits. Kidney Int. 1988 Jun;33(6):1078-83. doi: 10.1038/ki.1988.114.
• Results Bakr AF. Prophylactic theophylline to prevent renal dysfunction in newborns exposed to perinatal asphyxia--a study in a developing country. Pediatr Nephrol. 2005 Sep;20(9):1249-52. doi: 10.1007/s00467-005-1980-z. Epub 2005 Jun 10.
• Results Ng GY, Baker EH, Farrer KF. Aminophylline as an adjunct diuretic for neonates--a case series. Pediatr Nephrol. 2005 Feb;20(2):220-2. doi: 10.1007/s00467-004-1692-9. Epub 2004 Dec 4.
• Results Jenik AG, Ceriani Cernadas JM, Gorenstein A, Ramirez JA, Vain N, Armadans M, Ferraris JR. A randomized, double-blind, placebo-controlled trial of the effects of prophylactic theophylline on renal function in term neonates with perinatal asphyxia. Pediatrics. 2000 Apr;105(4):E45. doi: 10.1542/peds.105.4.e45.
• Results Bhat MA, Shah ZA, Makhdoomi MS, Mufti MH. Theophylline for renal function in term neonates with perinatal asphyxia: a randomized, placebo-controlled trial. J Pediatr. 2006 Aug;149(2):180-4. doi: 10.1016/j.jpeds.2006.03.053.
• Results McLaughlin GE, Abitbol CL. Reversal of oliguric tacrolimus nephrotoxicity in children. Nephrol Dial Transplant. 2005 Jul;20(7):1471-5. doi: 10.1093/ndt/gfh785. Epub 2005 Apr 19.
• Results Kramer BK, Preuner J, Ebenburger A, Kaiser M, Bergner U, Eilles C, Kammerl MC, Riegger GA, Birnbaum DE. Lack of renoprotective effect of theophylline during aortocoronary bypass surgery. Nephrol Dial Transplant. 2002 May;17(5):910-5. doi: 10.1093/ndt/17.5.910.
• Results Mahaldar AR, Sampathkumar K, Raghuram AR, Kumar S, Ramakrishnan M, Mahaldar DA. Risk prediction of acute kidney injury in cardiac surgery and prevention using aminophylline. Indian J Nephrol. 2012 May;22(3):179-83. doi: 10.4103/0971-4065.98752.
• Results Aki Y, Tomohiro A, Nishiyama A, Kiyomoto K, Kimura S, Abe Y. Effects of KW-3902, a selective and potent adenosine A1 receptor antagonist, on renal hemodynamics and urine formation in anesthetized dogs. Pharmacology. 1997 Oct;55(4):193-201. doi: 10.1159/000139528.
• Results Yao K, Ina Y, Nagashima K, Ohno T, Karasawa A. Effect of the selective adenosine A1-receptor antagonist KW-3902 on lipopolysaccharide-induced reductions in urine volume and renal blood flow in anesthetized dogs. Jpn J Pharmacol. 2000 Nov;84(3):310-5. doi: 10.1254/jjp.84.310.
• Results Givertz MM, Massie BM, Fields TK, Pearson LL, Dittrich HC; CKI-201 and CKI-202 Investigators. The effects of KW-3902, an adenosine A1-receptor antagonist,on diuresis and renal function in patients with acute decompensated heart failure and renal impairment or diuretic resistance. J Am Coll Cardiol. 2007 Oct 16;50(16):1551-60. doi: 10.1016/j.jacc.2007.07.019. Epub 2007 Oct 1.
• Results Cotter G, Dittrich HC, Weatherley BD, Bloomfield DM, O'Connor CM, Metra M, Massie BM; Protect Steering Committee, Investigators, and Coordinators. The PROTECT pilot study: a randomized, placebo-controlled, dose-finding study of the adenosine A1 receptor antagonist rolofylline in patients with acute heart failure and renal impairment. J Card Fail. 2008 Oct;14(8):631-40. doi: 10.1016/j.cardfail.2008.08.010. Epub 2008 Sep 14.
• Results Massie BM, O'Connor CM, Metra M, Ponikowski P, Teerlink JR, Cotter G, Weatherley BD, Cleland JG, Givertz MM, Voors A, DeLucca P, Mansoor GA, Salerno CM, Bloomfield DM, Dittrich HC; PROTECT Investigators and Committees. Rolofylline, an adenosine A1-receptor antagonist, in acute heart failure. N Engl J Med. 2010 Oct 7;363(15):1419-28. doi: 10.1056/NEJMoa0912613.
• Results Voors AA, Dittrich HC, Massie BM, DeLucca P, Mansoor GA, Metra M, Cotter G, Weatherley BD, Ponikowski P, Teerlink JR, Cleland JG, O'Connor CM, Givertz MM. Effects of the adenosine A1 receptor antagonist rolofylline on renal function in patients with acute heart failure and renal dysfunction: results from PROTECT (Placebo-Controlled Randomized Study of the Selective Adenosine A1 Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function). J Am Coll Cardiol. 2011 May 10;57(19):1899-907. doi: 10.1016/j.jacc.2010.11.057.
• Results Morecroft I, Dempsie Y, Bader M, Walther DJ, Kotnik K, Loughlin L, Nilsen M, MacLean MR. Effect of tryptophan hydroxylase 1 deficiency on the development of hypoxia-induced pulmonary hypertension. Hypertension. 2007 Jan;49(1):232-6. doi: 10.1161/01.HYP.0000252210.58849.78. Epub 2006 Nov 27.
• Results Sole MJ, Madapallimattam A, Baines AD. An active pathway for serotonin synthesis by renal proximal tubules. Kidney Int. 1986 Mar;29(3):689-94. doi: 10.1038/ki.1986.53.

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