title: Association of elevated urinary concentration of renin-angiotensin system components and severe AKI.
abstract: BACKGROUND
  Prognostic biomarkers that predict the severity of AKI at an early time point are needed. Urinary angiotensinogen was recently identified as a prognostic AKI biomarker. The study hypothesis is that urinary renin could also predict AKI severity and that in combination angiotensinogen and renin would be a strong predictor of prognosis at the time of AKI diagnosis.
  
  
  METHODS
  In this multicenter, retrospective cohort study, urine was obtained from 204 patients who developed AKI after cardiac surgery from August 2008 to June 1, 2012. All patients were classified as having Acute Kidney Injury Network (AKIN) stage 1 disease by serum creatinine criteria at the time of sample collection. Urine output was not used for staging. Urinary angiotensinogen and renin were measured, and the area under the receiver-operating characteristic curve (AUC) was used to test for prediction of progression to AKIN stage 3 or in-hospital 30-day mortality. These biomarkers were added stepwise to a clinical model, and improvement in prognostic predictive performance was evaluated by category free net reclassification improvement (cfNRI) and chi-squared automatic interaction detection (CHAID).
  
  
  RESULTS
  Both the urinary angiotensinogen-to-creatinine ratio (uAnCR; AUC, 0.75; 95% confidence interval [CI], 0.65 to 0.85) and the urinary renin-to-creatinine ratio (uRenCR; AUC, 0.70; 95% CI, 0.57 to 0.83) predicted AKIN stage 3 or death. Addition of uAnCR to a clinical model substantially improved prediction of the outcome (AUC, 0.85; cfNRI, 0.673), augmenting sensitivity and specificity. Further addition of uRenCR increased the sensitivity of the model (cfNRI(events), 0.44). CHAID produced a highly accurate model (AUC, 0.91) and identified the combination of uAnCR >337.89 ng/mg and uRenCR >893.41 pg/mg as the strongest predictors (positive predictive value, 80.4%; negative predictive value, 90.7%; accuracy, 90.2%).
  
  
  CONCLUSIONS
  The combination of urinary angiotensinogen and renin predicts progression to very severe disease in patients with early AKI after cardiac surgery.
authors.affiliation: Medical University of South Carolina, Charleston, South Carolina;, †University of Tennessee College of Medicine in Chattanooga, Chattanooga, Tennessee;, ‡George Washington University, Washington, DC;, §Duke University, Durham, North Carolina;, ‖Durham Veterans Affairs Medical Center, Durham, North Carolina, ¶Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Alge
authors.forename: Nithin
authors.initials: N
authors.lastname: Karakala
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Neely
authors.forename: Michael G
authors.initials: MG
authors.lastname: Janech
authors.forename: James A
authors.initials: JA
authors.lastname: Tumlin
authors.forename: Lakhmir S
authors.initials: LS
authors.lastname: Chawla
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Shaw
authors.forename: John M
authors.initials: JM
authors.lastname: Arthur
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000652:urine*; D000368:Aged; D000808:Angiotensinogen / Q000652:urine*; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood / Q000652:urine; D006348:Cardiac Surgical Procedures / Q000009:adverse effects; D016009:Chi-Square Distribution; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D012372:ROC Curve; D012083:Renin / Q000652:urine*; D012084:Renin-Angiotensin System; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D014481:United States; D015854:Up-Regulation
chemical_list: C534931:AGT protein, human; D015415:Biomarkers; D000808:Angiotensinogen; D003404:Creatinine; D012083:Renin