@article{c865ce37af534a91a4e1df596c10cd92,
title = "Uric Acid and Acute Kidney Injury in the Critically Ill",
abstract = "Rationale & Objective: Uric acid is excreted by the kidney and accumulates in acute kidney injury (AKI). Whether higher plasma uric acid level predisposes to AKI or its complications is not known. Study Design: Prospective observational cohort study. Setting & Participants: 2 independent cohorts of critically ill patients: (1)208 patients without AKI admitted to the intensive care unit (ICU)at Brigham & Women's Hospital between October 2008 and December 2016; and (2)250 participants with AKI requiring renal replacement therapy (RRT)who had not yet initiated RRT enrolled in the Acute Renal Failure Trial Network (ATN)Study. Exposure: Plasma uric acid level upon ICU admission and before RRT initiation in the ICU and ATN Study cohorts, respectively. Outcomes: Incident AKI and 60-day mortality in the ICU and ATN Study cohorts, respectively. Analytical Approach: Logistic regression models were used to test the association of plasma uric acid level with incident AKI and 60-day mortality. Results: In the ICU cohort, median plasma uric acid level was 4.7 (interquartile range [IQR], 3.6-6.4)mg/dL, and 40 patients (19.2%)developed AKI. Higher plasma uric acid levels associated with incident AKI, but this association was confounded by serum creatinine level and was not significant after multivariable adjustment (adjusted OR per doubling of uric acid, 1.50; 95% CI, 0.80-2.81). In the ATN Study cohort, median plasma uric acid level was 11.1 (IQR, 8.6–14.2)mg/dL, and 125 participants (50.0%)died within 60 days. There was no statistically significant association between plasma uric acid levels and 60-day mortality in either unadjusted models or after multivariable adjustment for demographic, severity-of-illness, and kidney-specific covariates (adjusted OR per doubling of uric acid, 1.15; 95% CI, 0.71-1.86). Limitations: Heterogeneity of ICU patients. Conclusions: Plasma uric acid levels upon ICU admission or before RRT initiation are not independently associated with adverse clinical outcomes in critically ill patients.",
keywords = "AKI, ICU, RRT, dialysis, uric acid",
author = "Anand Srivastava and Ragnar Palsson and Leaf, {David E.} and Angelica Higuera and Chen, {Margaret E.} and Polly Palacios and Baron, {Rebecca M.} and Venkata Sabbisetti and Hoofnagle, {Andrew N.} and Vaingankar, {Sucheta M.} and Palevsky, {Paul M.} and Waikar, {Sushrut S.}",
note = "Funding Information: The ATN Study was performed by the ATN Study Investigators and supported by the Cooperative Studies Program of the Department of Veterans Affairs ( VA ) Office of Research and Development and the NIDDK . This report does not necessarily reflect the opinions or views of the ATN Study investigators, VA, or NIDDK. The funders of this study had no role in the study design; collection, analysis, or interpretation of data; drafting of the manuscript; or decision to submit the manuscript for publication. Funding Information: This work was supported by National Institutes of Health ( NIH ) grant F32DK111066 (Dr Srivastava). Dr Palsson is supported by an American Society of Nephrology Research Fellowship Grant. Dr Leaf is supported by NIH grant K23DK106448, and Dr Waikar is supported by NIH grants U01DK085660, U01DK104308, R01DK103784, and UG3DK114915. Funding Information: Anand Srivastava, MD, MPH, Ragnar Palsson, MD, David E. Leaf, MD, MMSc, Angelica Higuera, MD, Margaret E. Chen, BS, Polly Palacios, MSPH, Rebecca M. Baron, MD, Venkata Sabbisetti, PhD, Andrew N. Hoofnagle, MD, PhD, Sucheta M. Vaingankar, PhD, Paul M. Palevsky, MD, and Sushrut S. Waikar, MD, MPH. Study design: AS, SSW; data acquisition: all authors; data analysis: AS, SSW; data interpretation: all authors. Each author also contributed important intellectual content during manuscript drafting or revision and ensured that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. This work was supported by National Institutes of Health (NIH)grant F32DK111066 (Dr Srivastava). Dr Palsson is supported by an American Society of Nephrology Research Fellowship Grant. Dr Leaf is supported by NIH grant K23DK106448, and Dr Waikar is supported by NIH grants U01DK085660, U01DK104308, R01DK103784, and UG3DK114915. Dr Srivastava has been a consultant for Horizon Pharma. Dr Palevsky has been a consultant for GE Healthcare, Baxter, Novartis, Healthspan Dx, and Durect. Dr Waikar received consulting fees for serving on the data safety monitoring board for Takeda, for trials involving uric acid–lowering agents; and consulting fees from the National Institutes of Health for serving as a medical monitor for a trial involving inosine to raise uric acid levels. The remaining authors declare that they have no relevant financial interests. We thank the ATN Study Investigators and National Institute of Diabetes and Digestive Diseases (NIDDK)data repository for the data used in this study; the following members of the ROCI who helped assemble this cohort: Drs Paul Dieffenbach, Samuel Ash, Laura Fredenburgh, and Joshua Englert; and the members of the Waikar Laboratory group at BWH for invaluable work. The ATN Study was performed by the ATN Study Investigators and supported by the Cooperative Studies Program of the Department of Veterans Affairs (VA)Office of Research and Development and the NIDDK. This report does not necessarily reflect the opinions or views of the ATN Study investigators, VA, or NIDDK. The funders of this study had no role in the study design; collection, analysis, or interpretation of data; drafting of the manuscript; or decision to submit the manuscript for publication. Part of this work was presented as a poster at the American Society of Nephrology Scientific Session in November 17, 2016, Chicago, IL. Received November 1, 2018. Evaluated by 2 external peer reviewers, with direct editorial and statistical input from an Associate Editor and the Editor-in-Chief. Accepted in revised form January 2, 2019. Publisher Copyright: {\textcopyright} 2019 The Authors",
year = "2019",
month = jan,
day = "1",
doi = "10.1016/j.xkme.2019.01.003",
language = "English (US)",
volume = "1",
pages = "21--30",
journal = "Kidney Medicine",
issn = "2590-0595",
publisher = "Elsevier Inc.",
number = "1",
}