Justin M Belcher1, Guadalupe Garcia-Tsao2, Arun J Sanyal3, Heather Thiessen-Philbrook4, Aldo J Peixoto5, Mark A Perazella5, Naheed Ansari6, Joseph Lim7, Steven G Coca1, Chirag R Parikh8. 1. Program of Applied Translational Research, Sections of Nephrology and Clinical Epidemiology Research Center, Veterans Affairs Medical Center, West Haven, Connecticut; 2. Clinical Epidemiology Research Center, Veterans Affairs Medical Center, West Haven, Connecticut; Digestive Diseases, Yale University School of Medicine, New Haven, Connecticut; Veterans Affairs-Connecticut Healthcare System, West Haven, Connecticut; 3. Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia; 4. Division of Nephrology, Department of Medicine, University of Western Ontario, London, Ontario, Canada; and. 5. Sections of Nephrology and Veterans Affairs-Connecticut Healthcare System, West Haven, Connecticut; 6. Division of Nephrology, Department of Internal Medicine, Jacobi Medical Center, South Bronx, New York. 7. Digestive Diseases, Yale University School of Medicine, New Haven, Connecticut; 8. Program of Applied Translational Research, Sections of Nephrology and Clinical Epidemiology Research Center, Veterans Affairs Medical Center, West Haven, Connecticut; chirag.parikh@yale.edu.
Abstract
BACKGROUND AND OBJECTIVES: AKI is a common and severe complication in patients with cirrhosis. AKI progression was previously shown to correlate with in-hospital mortality. Therefore, accurately predicting which patients are at highest risk for AKI progression may allow more rapid and targeted treatment. Urinary biomarkers of structural kidney injury associate with AKI progression and mortality in multiple settings of AKI but their prognostic performance in patients with liver cirrhosis is not well known. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A multicenter, prospective cohort study was conducted at four tertiary care United States medical centers between 2009 and 2011. The study comprised patients with cirrhosis and AKI defined by the AKI Network criteria evaluating structural (neutrophil gelatinase-associated lipocalin, IL-18, kidney injury molecule-1 [KIM-1], liver-type fatty acid-binding protein [L-FABP], and albuminuria) and functional (fractional excretion of sodium [FENa]) urinary biomarkers as predictors of AKI progression and in-hospital mortality. RESULTS: Of 188 patients in the study, 44 (23%) experienced AKI progression alone and 39 (21%) suffered both progression and death during their hospitalization. Neutrophil gelatinase-associated lipocalin, IL-18, KIM-1, L-FABP, and albuminuria were significantly higher in patients with AKI progression and death. These biomarkers were independently associated with this outcome after adjusting for key clinical variables including model of end stage liver disease score, IL-18 (relative risk [RR], 4.09; 95% confidence interval [95% CI], 1.56 to 10.70), KIM-1 (RR, 3.13; 95% CI, 1.20 to 8.17), L-FABP (RR, 3.43; 95% CI, 1.54 to 7.64), and albuminuria (RR, 2.07; 95% CI, 1.05-4.10) per log change. No biomarkers were independently associated with progression without mortality. FENa demonstrated no association with worsening of AKI. When added to a robust clinical model, only IL-18 independently improved risk stratification on a net reclassification index. CONCLUSIONS: Multiple structural biomarkers of kidney injury, but not FENa, are independently associated with progression of AKI and mortality in patients with cirrhosis. Injury marker levels were similar between those without progression and those with progression alone.
BACKGROUND AND OBJECTIVES: AKI is a common and severe complication in patients with cirrhosis. AKI progression was previously shown to correlate with in-hospital mortality. Therefore, accurately predicting which patients are at highest risk for AKI progression may allow more rapid and targeted treatment. Urinary biomarkers of structural kidney injury associate with AKI progression and mortality in multiple settings of AKI but their prognostic performance in patients with liver cirrhosis is not well known. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A multicenter, prospective cohort study was conducted at four tertiary care United States medical centers between 2009 and 2011. The study comprised patients with cirrhosis and AKI defined by the AKI Network criteria evaluating structural (neutrophil gelatinase-associated lipocalin, IL-18, kidney injury molecule-1 [KIM-1], liver-type fatty acid-binding protein [L-FABP], and albuminuria) and functional (fractional excretion of sodium [FENa]) urinary biomarkers as predictors of AKI progression and in-hospital mortality. RESULTS: Of 188 patients in the study, 44 (23%) experienced AKI progression alone and 39 (21%) suffered both progression and death during their hospitalization. Neutrophil gelatinase-associated lipocalin, IL-18, KIM-1, L-FABP, and albuminuria were significantly higher in patients with AKI progression and death. These biomarkers were independently associated with this outcome after adjusting for key clinical variables including model of end stage liver disease score, IL-18 (relative risk [RR], 4.09; 95% confidence interval [95% CI], 1.56 to 10.70), KIM-1 (RR, 3.13; 95% CI, 1.20 to 8.17), L-FABP (RR, 3.43; 95% CI, 1.54 to 7.64), and albuminuria (RR, 2.07; 95% CI, 1.05-4.10) per log change. No biomarkers were independently associated with progression without mortality. FENa demonstrated no association with worsening of AKI. When added to a robust clinical model, only IL-18 independently improved risk stratification on a net reclassification index. CONCLUSIONS: Multiple structural biomarkers of kidney injury, but not FENa, are independently associated with progression of AKI and mortality in patients with cirrhosis. Injury marker levels were similar between those without progression and those with progression alone.
Authors: Michael Haase; Prasad Devarajan; Anja Haase-Fielitz; Rinaldo Bellomo; Dinna N Cruz; Gebhard Wagener; Catherine D Krawczeski; Jay L Koyner; Patrick Murray; Michael Zappitelli; Stuart L Goldstein; Konstantinos Makris; Claudio Ronco; Johan Martensson; Claes-Roland Martling; Per Venge; Edward Siew; Lorraine B Ware; T Alp Ikizler; Peter R Mertens Journal: J Am Coll Cardiol Date: 2011-04-26 Impact factor: 24.094
Authors: Andrew J Portal; Mark J W McPhail; Matthew Bruce; Iona Coltart; Andrew Slack; Roy Sherwood; Nigel D Heaton; Debbie Shawcross; Julia A Wendon; Michael A Heneghan Journal: Liver Transpl Date: 2010-11 Impact factor: 5.799
Authors: Patrick G Northup; Curtis K Argo; Mihir R Bakhru; Timothy M Schmitt; Carl L Berg; Mitchell H Rosner Journal: Liver Transpl Date: 2010-04 Impact factor: 5.799
Authors: Gebhard Wagener; Moury Minhaz; Fallon A Mattis; Mihwa Kim; Jean C Emond; H Thomas Lee Journal: Nephrol Dial Transplant Date: 2011-01-21 Impact factor: 5.992
Authors: Edward D Siew; T Alp Ikizler; Tebeb Gebretsadik; Ayumi Shintani; Nancy Wickersham; Frederick Bossert; Josh F Peterson; Chirag R Parikh; Addison K May; Lorraine B Ware Journal: Clin J Am Soc Nephrol Date: 2010-06-17 Impact factor: 8.237
Authors: Florence Wong; Mitra K Nadim; John A Kellum; Francesco Salerno; Rinaldo Bellomo; Alexander Gerbes; Paolo Angeli; Richard Moreau; Andrew Davenport; Rajiv Jalan; Claudio Ronco; Yuri Genyk; Vicente Arroyo Journal: Gut Date: 2011-02-15 Impact factor: 23.059
Authors: Edward D Siew; Michael E Matheny; T Alp Ikizler; Julie B Lewis; Randolph A Miller; Lemuel R Waitman; Alan S Go; Chirag R Parikh; Josh F Peterson Journal: Kidney Int Date: 2009-12-30 Impact factor: 10.612
Authors: Natalie Gasterich; Sophie Wetz; Stefan Tillmann; Lena Fein; Anke Seifert; Alexander Slowik; Ralf Weiskirchen; Adib Zendedel; Andreas Ludwig; Steffen Koschmieder; Cordian Beyer; Tim Clarner Journal: J Mol Neurosci Date: 2020-09-21 Impact factor: 3.444