Acute kidney injury is a frequent complication in critically ill neonates receiving extracorporeal membrane oxygenation: a 14-year cohort study

Alexandra J M Zwiers, Saskia N de Wildt, Wim C J Hop, Eiske M Dorresteijn, Saskia J Gischler, Dick Tibboel, Karlien Cransberg, Alexandra J M Zwiers, Saskia N de Wildt, Wim C J Hop, Eiske M Dorresteijn, Saskia J Gischler, Dick Tibboel, Karlien Cransberg

Abstract

Introduction: Newborns in need of extracorporeal membrane oxygenation (ECMO) support are at high risk of developing acute kidney injury (AKI). AKI may occur as part of multiple organ failure and can be aggravated by exposure to components of the extracorporeal circuit. AKI necessitates adjustment of dosage of renally eliminated drugs and avoidance of nephrotoxic drugs. We aimed to define systematically the incidence and clinical course of AKI in critically ill neonates receiving ECMO support.

Methods: This study reviewed prospectively collected clinical data (including age, diagnosis, ECMO course, and serum creatinine (SCr)) of all ECMO-treated neonates within our institution spanning a 14-year period. AKI was defined by using the Risk, Injury, Failure, Loss of renal function, and End-stage renal disease (RIFLE) classification. SCr data were reviewed per ECMO day and compared with age-specific SCr reference values. Accordingly, patients were assigned to RIFLE categories (Risk, Injury, or Failure as 150%, 200%, or 300% of median SCr reference values). Data are presented as median and interquartile range (IQR) or number and percentage.

Results: Of 242 patients included, 179 (74%) survived. Median age at the start of ECMO was 39 hours (IQR, 26 to 63); median ECMO duration was 5.8 days (IQR, 3.9 to 9.4). In total, 153 (64%) patients had evidence of AKI, with 72 (30%) qualifying as Risk, 55 (23%) as Injury, and 26 (11%) as Failure. At the end of the study period, only 71 (46%) patients of all 153 AKI patients improved by at least one RIFLE category. With regression analysis, it was found that nitric oxide ventilation (P = 0.04) and younger age at the start of ECMO (P = 0.004) were significant predictors of AKI. Survival until intensive care unit discharge was significantly lower for patients in the Failure category (35%) as compared with the Non-AKI (78%), Risk (82%), and Injury category (76%), with all P < 0.001, whereas no significant differences were found between the three latter RIFLE categories.

Conclusions: Two thirds of neonates receiving ECMO had AKI, with a significantly increased mortality risk for patients in the Failure category. As AKI during childhood may predispose to chronic kidney disease in adulthood, long-term monitoring of kidney function after ECMO is warranted.

Figures

Figure 1
Figure 1
Patient inclusion flowchart. Flowchart detailing inclusion and exclusion criteria for patients treated with extracorporeal membrane oxygenation (ECMO) that resulted in the final study cohort. n, number of ECMO patients; AKI, acute kidney injury; ECMO, extracorporeal membrane oxygenation; 24h, 24 hours.
Figure 2
Figure 2
Evolution of acute kidney injury during extracorporeal membrane oxygenation (ECMO). Flow diagram showing the evolution of acute kidney injury (AKI) during treatment with ECMO. After the start of ECMO, all patients were stratified according to the highest RIFLE score attained. RIFLE categories Risk, Injury, and Failure were defined as, respectively, SCr above 150%, 200%, and 300%, of the median of age-specific SCr reference values. Subsequently the AKI evolution over time was evaluated by using the last RIFLE score before the cessation of ECMO or on ECMO day 12. All arrows indicate the direction of AKI evolution. Of all 153 AKI patients, only 71 (46%) patients improved at least one RIFLE category. n, number of ECMO patients (%); AKI, acute kidney injury; NS, nonsurvivor; RIFLE, Risk, Injury, Failure, Loss, End-stage renal disease; SCr, serum creatinine; S, survivor.
Figure 3
Figure 3
Kaplan-Meier survival curves stratified by RIFLE category. All patients are stratified according to the highest RIFLE score attained during ECMO. Kaplan-Meier analysis estimates, for each RIFLE category, the rate of survival until intensive care unit (ICU) discharge among all patients after the cessation of ECMO. RIFLE categories Risk, Injury, and Failure were defined as, respectively, SCr above 150%, 200%, and 300%, of the median of age-specific SCr reference values. The differences between the Failure category and each of the other RIFLE categories are significant (all P < 0.001; Log-Rank test). No significant differences were found between the Non-AKI, Risk, and Injury categories. ECMO, extracorporeal membrane oxygenation; ICU, intensive care unit; RIFLE, Risk, Injury, Failure, Loss, End-stage renal disease; SCr, serum creatinine.
Figure 4
Figure 4
RIFLE distribution per day of ECMO treatment grouped according to survival. The distribution of RIFLE categories on each ECMO day for patients who survived until intensive care unit (ICU) discharge compared with patients who did not survive until ICU discharge. RIFLE categories Risk, Injury, and Failure were defined as, respectively, SCr above 150%, 200%, and 300%, of the median of age-specific SCr reference values. Differences in RIFLE distribution per ECMO day between survivors and nonsurvivors were assessed by using Mann-Whitney U tests; *P < 0.05; **P < 0.01. Survivors generally had a better RIFLE category throughout ECMO. ECMO, extracorporeal membrane oxygenation; ICU, intensive care unit; RIFLE, Risk, Injury, Failure, Loss, End-stage renal disease; SCr, serum creatinine.

References

    1. Michel CC. Transport of macromolecules through microvascular walls. Cardiovasc Res. 1996;17:644–653.
    1. Stahl RF, Fisher CA, Kucich U, Weinbaum G, Warsaw DS, Stenach N, O'Connor C, Addonizio VP. Effects of simulated extracorporeal circulation on human leukocyte elastase release, superoxide generation, and procoagulant activity. J Thorac Cardiovasc Surg. 1991;17:230–239.
    1. Alkandari O, Eddington KA, Hyder A, Gauvin F, Ducruet T, Gottesman R, Phan V, Zappitelli M. Acute kidney injury is an independent risk factor for pediatric intensive care unit mortality, longer length of stay and prolonged mechanical ventilation in critically ill children: a two-center retrospective cohort study. Crit Care. 2011;17:R146. doi: 10.1186/cc10269.
    1. Bailey D, Phan V, Litalien C, Ducruet T, Merouani A, Lacroix J, Gauvin F. Risk factors of acute renal failure in critically ill children: a prospective descriptive epidemiological study. Pediatr Crit Care Med. 2007;17:29–35. doi: 10.1097/01.pcc.0000256612.40265.67.
    1. Akcan-Arikan A, Zappitelli M, Loftis LL, Washburn KK, Jefferson LS, Goldstein SL. Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int. 2007;17:1028–1035. doi: 10.1038/sj.ki.5002231.
    1. Schneider J, Khemani R, Grushkin C, Bart R. Serum creatinine as stratified in the RIFLE score for acute kidney injury is associated with mortality and length of stay for children in the pediatric intensive care unit. Crit Care Med. 2010;17:933–939. doi: 10.1097/CCM.0b013e3181cd12e1.
    1. Plotz FB, Bouma AB, van Wijk JA, Kneyber MC, Bokenkamp A. Pediatric acute kidney injury in the ICU: an independent evaluation of pRIFLE criteria. Intensive Care Med. 2008;17:1713–1717. doi: 10.1007/s00134-008-1176-7.
    1. Koralkar R, Ambalavanan N, Levitan EB, McGwin G, Goldstein S, Askenazi D. Acute kidney injury reduces survival in very low birth weight infants. Pediatr Res. 2011;17:354–358. doi: 10.1203/PDR.0b013e31820b95ca.
    1. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute Dialysis Quality Initiative. Acute renal failure: definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004;17:R204–R212. doi: 10.1186/cc2872.
    1. Lopes JA, Fernandes P, Jorge S, Goncalves S, Alvarez A, Costa e Silva Z, Franca C, Prata MM. Acute kidney injury in intensive care unit patients: a comparison between the RIFLE and the Acute Kidney Injury Network classifications. Crit Care. 2008;17:R110. doi: 10.1186/cc6997.
    1. Lin CY, Chen YC, Tsai FC, Tian YC, Jenq CC, Fang JT, Yang CW. RIFLE classification is predictive of short-term prognosis in critically ill patients with acute renal failure supported by extracorporeal membrane oxygenation. Nephrol Dial Transplant. 2006;17:2867–2873. doi: 10.1093/ndt/gfl326.
    1. Gadepalli SK, Selewski DT, Drongowski RA, Mychaliska GB. Acute kidney injury in congenital diaphragmatic hernia requiring extracorporeal life support: an insidious problem. J Pediatr Surg. 2011;17:630–635. doi: 10.1016/j.jpedsurg.2010.11.031.
    1. Thiagarajan RR, Laussen PC, Rycus PT, Bartlett RH, Bratton SL. Extracorporeal membrane oxygenation to aid cardiopulmonary resuscitation in infants and children. Circulation. 2007;17:1693–1700. doi: 10.1161/CIRCULATIONAHA.106.680678.
    1. Askenazi DJ, Ambalavanan N, Hamilton K, Cutter G, Laney D, Kaslow R, Georgeson K, Barnhart DC, Dimmitt RA. Acute kidney injury and renal replacement therapy independently predict mortality in neonatal and pediatric noncardiac patients on extracorporeal membrane oxygenation. Pediatr Crit Care Med. 2011;17:e1–e6. doi: 10.1097/PCC.0b013e3181d8e348.
    1. Blijdorp K, Cransberg K, Wildschut ED, Gischler SJ, Jan Houmes R, Wolff ED, Tibboel D. Haemofiltration in newborns treated with extracorporeal membrane oxygenation: a case-comparison study. Crit Care. 2009;17:R48. doi: 10.1186/cc7771.
    1. Junge W, Wilke B, Halabi A, Klein G. Determination of reference intervals for serum creatinine, creatinine excretion and creatinine clearance with an enzymatic and a modified Jaffe method. Clin Chim Acta. 2004;17:137–148. doi: 10.1016/j.cccn.2004.02.007.
    1. Boer DP, de Rijke YB, Hop WC, Cransberg K, Dorresteijn EM. Reference values for serum creatinine in children younger than 1 year of age. Pediatr Nephrol. 2010;17:2107–2113. doi: 10.1007/s00467-010-1533-y.
    1. van der Vorst MM, den Hartigh J, Wildschut E, Tibboel D, Burggraaf J. An exploratory study with an adaptive continuous intravenous furosemide regimen in neonates treated with extracorporeal membrane oxygenation. Crit Care. 2007;17:R111. doi: 10.1186/cc6146.
    1. van der Vorst MM, Wildschut E, Houmes RJ, Gischler SJ, Kist-van Holthe JE, Burggraaf J, van der Heijden AJ, Tibboel D. Evaluation of furosemide regimens in neonates treated with extracorporeal membrane oxygenation. Crit Care. 2006;17:R168. doi: 10.1186/cc5115.
    1. Smith AH, Hardison DC, Worden CR, Fleming GM, Taylor MB. Acute renal failure during extracorporeal support in the pediatric cardiac patient. ASAIO J. 2009;17:412–416. doi: 10.1097/MAT.0b013e31819ca3d0.
    1. Prowle J, Bagshaw SM, Bellomo R. Renal blood flow, fractional excretion of sodium and acute kidney injury: time for a new paradigm? Curr Opin Crit Care. 2012;17:585–592. doi: 10.1097/MCC.0b013e328358d480.
    1. Hei F, Lou S, Li J, Yu K, Liu J, Feng Z, Zhao J, Hu S, Xu J, Chang Q, Liu Y, Wang X, Liu P, Long C. Five-year results of 121 consecutive patients treated with extracorporeal membrane oxygenation at Fu Wai Hospital. Artif Organs. 2011;17:572–578. doi: 10.1111/j.1525-1594.2010.01151.x.
    1. Goldstein SL. Acute kidney injury in children and its potential consequences in adulthood. Blood Purif. 2012;17:131–137. doi: 10.1159/000334143.
    1. Goldstein SL, Devarajan P. Acute kidney injury in childhood: should we be worried about progression to CKD? Pediatr Nephrol. 2011;17:509–522. doi: 10.1007/s00467-010-1653-4.
    1. Paden ML, Warshaw BL, Heard ML, Fortenberry JD. Recovery of renal function and survival after continuous renal replacement therapy during extracorporeal membrane oxygenation. Pediatr Crit Care Med. 2011;17:153–158. doi: 10.1097/PCC.0b013e3181e2a596.
    1. Han WK, Waikar SS, Johnson A, Betensky RA, Dent CL, Devarajan P, Bonventre JV. Urinary biomarkers in the early diagnosis of acute kidney injury. Kidney Int. 2008;17:863–869. doi: 10.1038/sj.ki.5002715.
    1. Krawczeski CD, Goldstein SL, Woo JG, Wang Y, Piyaphanee N, Ma Q, Bennett M, Devarajan P. Temporal relationship and predictive value of urinary acute kidney injury biomarkers after pediatric cardiopulmonary bypass. J Am Coll Cardiol. 2011;17:2301–2309. doi: 10.1016/j.jacc.2011.08.017.
    1. Ricci Z, Morelli S, Favia I, Garisto C, Brancaccio G, Picardo S. Neutrophil gelatinase-associated lipocalin levels during extracorporeal membrane oxygenation in critically ill children with congenital heart disease: preliminary experience. Pediatr Crit Care Med. 2012;17:e51–e54. doi: 10.1097/PCC.0b013e3181fe4717.
    1. Soni SS, Ronco C, Katz N, Cruz DN. Early diagnosis of acute kidney injury: the promise of novel biomarkers. Blood Purif. 2009;17:165–174. doi: 10.1159/000227785.

Source: PubMed

3
Tilaa