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

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.

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

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

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

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.