title: Urinary Biomarkers at the Time of AKI Diagnosis as Predictors of Progression of AKI among Patients with Acute Cardiorenal Syndrome.
abstract: A major challenge in early treatment of acute cardiorenal syndrome (CRS) is the lack of predictors for progression of AKI. We aim to investigate the utility of urinary angiotensinogen and other renal injury biomarkers in predicting AKI progression in CRS.
  
  
  
  In this prospective, multicenter study, we screened 732 adults who admitted for acute decompensated heart failure from September 2011 to December 2014, and evaluated whether renal injury biomarkers measured at time of AKI diagnosis can predict worsening of AKI. In 213 patients who developed Kidney Disease Improving Global Outcomes stage 1 or 2 AKI, six renal injury biomarkers, including urinary angiotensinogen (uAGT), urinary neutrophil gelatinase-associated lipocalin (uNGAL), plasma neutrophil gelatinase-associated lipocalin, urinary IL-18 (uIL-18), urinary kidney injury molecule-1, and urinary albumin-to-creatinine ratio, were measured at time of AKI diagnosis. The primary outcome was AKI progression defined by worsening of AKI stage (50 patients). The secondary outcome was AKI progression with subsequent death (18 patients).
  
  
  
  After multivariable adjustment, the highest tertile of three urinary biomarkers remained associated with AKI progression compared with the lowest tertile: uAGT (odds ratio [OR], 10.8; 95% confidence interval [95% CI], 3.4 to 34.7), uNGAL (OR, 4.7; 95% CI, 1.7 to 13.4), and uIL-18 (OR, 3.6; 95% CI, 1.4 to 9.5). uAGT was the best predictor for both primary and secondary outcomes with area under the receiver operating curve of 0.78 and 0.85. These three biomarkers improved risk reclassification compared with the clinical model alone, with uAGT performing the best (category-free net reclassification improvement for primary and secondary outcomes of 0.76 [95% CI, 0.46 to 1.06] and 0.93 [95% CI, 0.50 to 1.36]; P<0.001). Excellent performance of uAGT was further confirmed with bootstrap internal validation.
  
  
  
  uAGT, uNGAL, and uIL-18 measured at time of AKI diagnosis improved risk stratification and identified CRS patients at highest risk of adverse outcomes.
authors.affiliation: Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangzhou, China.|Department of Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Cardiovascular Institute, Guangzhou, China.
authors.forename: Chunbo
authors.initials: C
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangzhou, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Yang
authors.affiliation: Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Department of Nephrology, Guizhou Provincial People's Hospital, Guiyang Medical University, Guiyang, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zha
authors.affiliation: Division of Nephrology, Institute of Nephrology, Guangdong Medical College, Zhanjiang, China.
authors.forename: Huafeng
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China; and.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Ma
authors.affiliation: Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangzhou, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Tian
authors.affiliation: Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangzhou, China.
authors.forename: Pingyan
authors.initials: P
authors.lastname: Chen
authors.affiliation: Division of Nephrology, The Futian Hospital, Guangdong Medical College, Shenzhen, China.
authors.forename: Tiecheng
authors.initials: T
authors.lastname: Yang
authors.affiliation: Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangzhou, China.
authors.forename: Fan Fan
authors.initials: FF
authors.lastname: Hou
mesh_terms: D000208:Acute Disease; D058186:Acute Kidney Injury / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology / Q000652:urine*; D000368:Aged; D000369:Aged, 80 and over; D000419:Albuminuria / Q000209:etiology / Q000652:urine; D000808:Angiotensinogen / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D059347:Cardio-Renal Syndrome / Q000150:complications*; D003404:Creatinine / Q000652:urine; D018450:Disease Progression; D005260:Female; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000378:metabolism; D006801:Humans; D020382:Interleukin-18 / Q000652:urine*; D000071068:Lipocalin-2 / Q000097:blood / Q000652:urine*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018570:Risk Assessment; D013997:Time Factors
chemical_list: D015415:Biomarkers; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D020382:Interleukin-18; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D000808:Angiotensinogen; D003404:Creatinine
keywords: Adult; Angiotensinogen; Area Under Curve; Cardio-Renal Syndrome; Humans; Prospective Studies; acute kidney injury; biomarkers; creatinine; outcomes; prediction