Randomized controlled trials involving natriuretic peptide administration in solid organ transplantation setting have shown inconsistent effects for renal endpoints. We conducted a systematic review and meta-analysis of these trials to ascertain the role of natriuretic peptides in the management of solid organ transplantation associated acute kidney injury (AKI). MEDLINE, EMBASE, and Google scholar were searched independently by two authors for randomized trials evaluating renal effects of natriuretic peptides in solid organ transplantation settings. Two reviewers independently assessed the studies for eligibility and extracted the relevant data. The pooled estimate showed that natriuretic peptide administration is associated with a reduction in AKI requiring dialysis (odds ratio = 0.50 [0.26–0.97]), a statistically nonsignificant trend toward improvement in posttransplant creatinine clearance (weighted mean difference = 5.5？mL/min, [？1.3 to 12.2？mL/min]), and reduction in renal replacement requirement duration (weighted mean difference ？44.0 hours, [？60.5 to ？27.5 hours]). There were no mortality events and no adverse events related to natriuretic peptides. In conclusion, administration of natriuretic peptides in solid organ transplantation may be associated with significant improvements in renal outcomes. These observations need to be confirmed in an adequately powered, prospective multicenter study. 1. Introduction Acute kidney injury (AKI) is common in hospitalized patients and is associated with significant morbidity and mortality [1, 2]. Despite recent advances, outcomes from AKI have not substantially changed in the last four decades and the incidence of AKI is on the rise [3]. Solid organ transplantation procedures (e.g., liver transplantation, heart transplantation, lung transplantation, and combined solid organ transplantations such as heart-lung transplant) are a recognized cause of AKI and renal transplantation is also frequently associated with AKI [4–10]. The incidence of AKI after liver transplantation reportedly ranges from 12% to 67% depending upon the definition used [4, 11]. Dialysis is required in up to 21% of the cases [4], and AKI in this setting is associated with higher mortality [4, 11]. Similarly, the incidence of AKI remains high in immediate postcardiac transplantation setting as up to 1/3rd of patients develop AKI [7]. Postischemic acute tubular necrosis is the most common cause of persistent renal failure (also known as delayed graft function) in the immediate postrenal transplant period and remains a major obstacle for
References
[1]
M. H. Rosner and M. D. Okusa, “Acute kidney injury associated with cardiac surgery,” Clinical Journal of the American Society of Nephrology, vol. 1, no. 1, pp. 19–32, 2006.
[2]
C. V. Thakar, A. Christianson, R. Freyberg, P. Almenoff, and M. L. Render, “Incidence and outcomes of acute kidney injury in intensive care units: a veterans administration study,” Critical Care Medicine, vol. 37, no. 9, pp. 2552–2558, 2009.
[3]
E. D. Siew and S. M. Deger, “Recent advances in acute kidney injury epidemiology,” Current Opinion in Nephrology and Hypertension, vol. 21, no. 3, pp. 309–317, 2012.
[4]
N. Akamatsu, Y. Sugawara, S. Tamura et al., “Prevention of renal impairment by continuous infusion of human atrial natriuretic peptide after liver transplantation,” Transplantation, vol. 80, no. 8, pp. 1093–1098, 2005.
[5]
J. M. Boyle, S. Moualla, S. Arrigain et al., “Risks and outcomes of acute kidney injury requiring dialysis after cardiac transplantation,” The American Journal of Kidney Diseases, vol. 48, no. 5, pp. 787–796, 2006.
[6]
J. M. Sands, J. F. Neylan, R. A. Olson, D. P. O'Brien, J. D. Whelchel, and W. E. Mitch, “Atrial natriuretic factor does not improve the outcome of cadaveric renal transplantation,” Journal of the American Society of Nephrology, vol. 1, no. 9, pp. 1081–1086, 1990.
[7]
P. T. T. Pham, C. Slavov, and P. C. T. Pham, “Acute kidney injury after liver, heart, and lung transplants: dialysis modality, predictors of renal function recovery, and impact on survival,” Advances in Chronic Kidney Disease, vol. 16, no. 4, pp. 256–267, 2009.
[8]
P. N. Rocha, A. T. Rocha, S. M. Palmer, R. D. Davis, and S. R. Smith, “Acute renal failure after lung transplantation: incidence, predictors and impact on perioperative morbidity and mortality,” The American Journal of Transplantation, vol. 5, no. 6, pp. 1469–1476, 2005.
[9]
A. Ishani, S. Erturk, M. I. Hertz, A. J. Matas, K. Savik, and M. E. Rosenberg, “Predictors of renal function following lung or heart-lung transplantation,” Kidney International, vol. 61, no. 6, pp. 2228–2234, 2002.
[10]
C. Clajus, N. Hanke, J. Gottlieb et al., “Renal comorbidity after solid organ and stem cell transplantation,” The American Journal of Transplantation, vol. 12, no. 7, pp. 1691–1699, 2012.
[11]
J. B. Cabezuelo, P. Ramirez, F. Acosta et al., “Prognostic factors of early acute renal failure in liver transplantation,” Transplantation Proceedings, vol. 34, no. 1, pp. 254–255, 2002.
[12]
A. Siedlecki, W. Irish, and D. C. Brennan, “Delayed graft function in the kidney transplant,” The American Journal of Transplantation, vol. 11, no. 11, pp. 2279–2296, 2011.
[13]
D. L. Vesely, “Natriuretic peptides and acute renal failure,” The American Journal of Physiology, vol. 285, no. 2, pp. F167–F177, 2003.
[14]
S. U. Nigwekar and J. K. Hix, “The role of natriuretic peptide administration in cardiovascular surgery-associated renal dysfunction: a systematic review and meta-analysis of randomized controlled trials,” Journal of Cardiothoracic and Vascular Anesthesia, vol. 23, no. 2, pp. 151–160, 2009.
[15]
S. U. Nigwekar, S. D. Navaneethan, C. R. Parikh, and J. K. Hix, “Atrial natriuretic peptide for preventing and treating acute kidney injury,” Cochrane Database of Systematic Reviews, no. 4, Article ID CD006028, 2009.
[16]
S. U. Nigwekar, S. D. Navaneethan, C. R. Parikh, and J. K. Hix, “Atrial natriuretic peptide for management of acute kidney injury: a systematic review and meta-analysis,” Clinical Journal of the American Society of Nephrology, vol. 4, no. 2, pp. 261–272, 2009.
[17]
S. U. Nigwekar and S. S. Waikar, “Diuretics in acute kidney injury,” Seminars in Nephrology, vol. 31, no. 6, pp. 523–534, 2011.
[18]
T. J. Opgenorth and E. I. Novosad, “Atrial natriuretic factor and endothelin interactions in control of vascular tone,” European Journal of Pharmacology, vol. 191, no. 3, pp. 351–357, 1990.
[19]
G. A. Sagnella, “Practical implications of current natriuretic peptide research,” Journal of the Renin-Angiotensin-Aldosterone System, vol. 1, no. 4, pp. 304–315, 2000.
[20]
M. Gagelmann, D. Hock, and W. G. Forssmann, “Urodilatin (CDD/ANP-95-126) is not biologically inactivated by a peptidase from dog kidney cortex membranes in contrast to atrial natriuretic peptide/cardiodilatin (α-hANP/CDD-99-126),” FEBS Letters, vol. 233, no. 2, pp. 249–254, 1988.
[21]
J. G. Lainchbury, J. C. Burnett Jr., D. Meyer, and M. M. Redfield, “Effects of natriuretic peptides on load and myocardial function in normal and heart failure dogs,” The American Journal of Physiology, vol. 278, no. 1, pp. H33–H40, 2000.
[22]
P. Brenner, M. Meyer, H. Reichenspurner et al., “Significance of prophylactic urodilatin (INN: ularitide) infusion for the prevention of acute renal failure in patients after heart transplantation,” European Journal of Medical Research, vol. 1, no. 3, pp. 137–143, 1995.
[23]
P. Gianello, M. Carlier, J. Jamart et al., “Effect of 1-28α-h atrial natriuretic peptide on acute renal failure in cadaveric renal transplantation,” Clinical Transplantation, vol. 9, no. 6, pp. 481–489, 1995.
[24]
E. R. Kuse, M. Meyer, R. Constantin et al., “Urodilatin (INN: ularitide). A novel peptide for the treatment of postoperative acute renal failure following liver transplantation,” Anaesthesist, vol. 45, no. 4, pp. 351–358, 1996.
[25]
J. M. Langrehr, A. Kahl, M. Meyer et al., “Prophylactic use of low-dose urodilatin for prevention of renal impairment following liver transplantation: a randomized placebo-controlled study,” Clinical Transplantation, vol. 11, no. 6, pp. 593–598, 1997.
[26]
P. J. Ratcliffe, A. J. Richardson, J. E. Kirby, C. Moyses, J. R. Shelton, and P. J. Morris, “Effect of intravenous infusion of atriopeptin 3 on immediate renal allograft function,” Kidney International, vol. 39, no. 1, pp. 164–168, 1991.
[27]
M. Kentsch, C. Drummer, R. Gerzer, and G. Muller-Esch, “Severe hypotension and bradycardia after continuous intravenous infusion of urodilatin (ANP 95–126) in a patient with congestive heart failure,” European Journal of Clinical Investigation, vol. 25, no. 4, pp. 281–283, 1995.
[28]
D. Moher, D. J. Cook, S. Eastwood, I. Olkin, D. Rennie, and D. F. Stroup, “Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement,” The Lancet, vol. 354, no. 9193, pp. 1896–1900, 1999.
[29]
A. R. Jadad, R. A. Moore, D. Carroll et al., “Assessing the quality of reports of randomized clinical trials: is blinding necessary?” Controlled Clinical Trials, vol. 17, no. 1, pp. 1–12, 1996.
[30]
R. L. Mehta, J. A. Kellum, S. V. Shah et al., “Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury,” Critical Care, vol. 11, no. 2, article R31, 2007.
[31]
P. G. S. Alderson and J. P. T. Higgins, Analysing and Presenting Results, The Cochrane Library, 2004.
[32]
J. P. T. Higgins, S. G. Thompson, J. J. Deeks, and D. G. Altman, “Measuring inconsistency in meta-analyses,” The British Medical Journal, vol. 327, no. 7414, pp. 557–560, 2003.
[33]
J. Lewis, M. M. Salem, G. M. Chertow et al., “Atrial natriuretic factor in oliguric acute renal failure,” The American Journal of Kidney Diseases, vol. 36, no. 4, pp. 767–774, 2000.
[34]
R. L. Allgren, “Update on clinical trials with atrial natriuretic peptide in acute tubular necrosis,” Renal Failure, vol. 20, no. 5, pp. 691–695, 1998.
[35]
D. L. Mattson, S. Lu, R. J. Roman, and A. W. Cowley Jr., “Relationship between renal perfusion pressure and blood flow in different regions of the kidney,” The American Journal of Physiology, vol. 264, no. 3, pp. R578–R583, 1993.
