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Impact of Early Acute Kidney Injury on Management and Outcome in Patients With Acute Respiratory Distress Syndrome: A Secondary Analysis of a Multicenter Observational Study*

McNicholas, Bairbre A. MD, PhD1,2,3; Rezoagli, Emanuele MD1,3,4; Pham, Tài MD, PhD5; Madotto, Fabiana PhD6; Guiard, Elsa MD, PhD7; Fanelli, Vito MD, PhD8; Bellani, Giacomo MD, PhD4; Griffin, Matthew D. MD PhD1,2; Ranieri, Marco MD, PhD9; Laffey, John G. MD, MA1,3; on behalf of the ESICM Trials Group and the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) Investigators

doi: 10.1097/CCM.0000000000003832
Clinical Investigations
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Objectives: To understand the impact of mild-moderate and severe acute kidney injury in patients with acute respiratory distress syndrome.

Design: Secondary analysis of the “Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure”, an international prospective cohort study of patients with severe respiratory failure.

Setting: Four-hundred fifty-nine ICUs from 50 countries across five continents.

Subjects: Patients with a glomerular filtration rate greater than 60 mL/min/1.73 m2 prior to admission who fulfilled criteria of acute respiratory distress syndrome on day 1 and day 2 of acute hypoxemic respiratory failure.

Interventions: Patients were categorized based on worst serum creatinine or urine output into: 1) no acute kidney injury (serum creatinine < 132 µmol/L or urine output ≥ 0.5 mL/kg/hr), 2) mild-moderate acute kidney injury (serum creatinine 132–354 µmol/L or minimum urine output between 0.3 and 0.5mL/kg/hr), or 3) severe acute kidney injury (serum creatinine > 354 µmol/L or renal replacement therapy or minimum urine output < 0.3 mL/kg/hr).

Measurements and Main Results: The primary outcome was hospital mortality, whereas secondary outcomes included prevalence of acute kidney injury and characterization of acute respiratory distress syndrome risk factors and illness severity patterns, in patients with acute kidney injury versus no acute kidney injury. One-thousand nine-hundred seventy-four patients met inclusion criteria: 1,209 (61%) with no acute kidney injury, 468 (24%) with mild-moderate acute kidney injury, and 297 (15%) with severe acute kidney injury. The impact of acute kidney injury on the ventilatory management of patients with acute respiratory distress syndrome was relatively limited, with no differences in arterial Co2 tension or in tidal or minute ventilation between the groups. Hospital mortality increased from 31% in acute respiratory distress syndrome patients with no acute kidney injury to 50% in mild-moderate acute kidney injury (p ≤ 0.001 vs no acute kidney injury) and 58% in severe acute kidney injury (p ≤ 0.001 vs no acute kidney injury and mild-moderate acute kidney injury). In multivariate analyses, both mild-moderate (odds ratio, 1.61; 95% CI, 1.24–2.09; p < 0.001) and severe (odds ratio, 2.13; 95% CI, 1.55–2.94; p < 0.001) acute kidney injury were independently associated with mortality.

Conclusions: The development of acute kidney injury, even when mild-moderate in severity, is associated with a substantial increase in mortality in patients with acute respiratory distress syndrome.

1Regenerative Medicine Institute (REMEDI) at CÚRAM Centre for Research in Medical Devices, School of Medicine, National University of Ireland, Galway, Galway, Ireland.

2Nephrology Services, Galway University Hospitals, SAOLTA University Healthcare Group, Galway, Ireland.

3Department of Anaesthesia and Intensive Care Medicine, Galway University Hospitals, SAOLTA University Healthcare Group, Galway, Ireland.

4Department of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy.

5Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, and Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Canada.

6Research Center on Public Health, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.

7Department of Nephrology, Toronto General Hospital UHN, Toronto, ON, Canada.

8Department of Anesthesia and Critical Care - AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.

9Department of Anesthesia and Intensive Care Medicine, Policlinico Umberto I, University “La Sapienza” of Rome, Rome, Italy.

*See also p. 1273.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Supported, in part, by the European Society of Intensive Care Medicine, Brussels, Belgium, by St Michael’s Hospital, Toronto, ON, Canada and by the University of Milan-Bicocca, Monza, Italy.

Dr. Laffey’s institution received funding from European Society of Intensive Care Medicine; St Michael’s Hospital, Toronto, ON, Canada; and University of Milan-Bicocca. Dr. Griffin received grant funding from Randox Laboratories (research related to biomarker assays for chronic kidney disease). The remaining authors have disclosed that they do not have any potential conflicts of interest.

A complete list of Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure steering committee, national coordinators, site investigators and national societies endorsing the study can be found in (Appendix 1, Supplemental Digital Content 1, http://links.lww.com/CCM/E614).

For information regarding this article, E-mail: john.laffey@nuigalway.ie

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