BACKGROUND: Biomarkers of AKI that can predict which patients will develop severe renal disease at the time of diagnosis will facilitate timely intervention in populations at risk of adverse outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Liquid chromatography/tandem mass spectrometry was used to identify 30 potential prognostic urinary biomarkers of severe AKI in a group of patients that developed AKI after cardiac surgery. Angiotensinogen had the best discriminative characteristics. Urinary angiotensinogen was subsequently measured by ELISA and its prognostic predictive power was verified in 97 patients who underwent cardiac surgery between August 1, 2008 and October 6, 2011. RESULTS: The urine angiotensinogen/creatinine ratio (uAnCR) predicted worsening of AKI, Acute Kidney Injury Network (AKIN) stage 3, need for renal replacement therapy, discharge >7 days from sample collection, and composite outcomes of AKIN stage 2 or 3, AKIN stage 3 or death, and renal replacement therapy or death. The prognostic predictive power of uAnCR was improved when only patients classified as AKIN stage 1 at the time of urine sample collection (n=79) were used in the analysis, among whom it predicted development of stage 3 AKI or death with an area under the curve of 0.81. Finally, category free net reclassification improvement showed that the addition of uAnCR to a clinical model to predict worsening of AKI improved the predictive power. CONCLUSIONS: Elevated uAnCR is associated with adverse outcomes in patients with AKI. These data are the first to demonstrate the utility of angiotensinogen as a prognostic biomarker of AKI after cardiac surgery.
BACKGROUND: Biomarkers of AKI that can predict which patients will develop severe renal disease at the time of diagnosis will facilitate timely intervention in populations at risk of adverse outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Liquid chromatography/tandem mass spectrometry was used to identify 30 potential prognostic urinary biomarkers of severe AKI in a group of patients that developed AKI after cardiac surgery. Angiotensinogen had the best discriminative characteristics. Urinary angiotensinogen was subsequently measured by ELISA and its prognostic predictive power was verified in 97 patients who underwent cardiac surgery between August 1, 2008 and October 6, 2011. RESULTS: The urine angiotensinogen/creatinine ratio (uAnCR) predicted worsening of AKI, Acute Kidney Injury Network (AKIN) stage 3, need for renal replacement therapy, discharge >7 days from sample collection, and composite outcomes of AKIN stage 2 or 3, AKIN stage 3 or death, and renal replacement therapy or death. The prognostic predictive power of uAnCR was improved when only patients classified as AKIN stage 1 at the time of urine sample collection (n=79) were used in the analysis, among whom it predicted development of stage 3 AKI or death with an area under the curve of 0.81. Finally, category free net reclassification improvement showed that the addition of uAnCR to a clinical model to predict worsening of AKI improved the predictive power. CONCLUSIONS: Elevated uAnCR is associated with adverse outcomes in patients with AKI. These data are the first to demonstrate the utility of angiotensinogen as a prognostic biomarker of AKI after cardiac surgery.
Authors: Chirag R Parikh; Steven G Coca; Heather Thiessen-Philbrook; Michael G Shlipak; Jay L Koyner; Zhu Wang; Charles L Edelstein; Prasad Devarajan; Uptal D Patel; Michael Zappitelli; Catherine D Krawczeski; Cary S Passik; Madhav Swaminathan; Amit X Garg Journal: J Am Soc Nephrol Date: 2011-08-11 Impact factor: 10.121
Authors: Jay L Koyner; Amit X Garg; Steven G Coca; Kyaw Sint; Heather Thiessen-Philbrook; Uptal D Patel; Michael G Shlipak; Chirag R Parikh Journal: J Am Soc Nephrol Date: 2012-03-01 Impact factor: 10.121
Authors: Isaac E Hall; Steven G Coca; Mark A Perazella; Umo U Eko; Randy L Luciano; Patricia R Peter; Won K Han; Chirag R Parikh Journal: Clin J Am Soc Nephrol Date: 2011-10-27 Impact factor: 8.237
Authors: V Y Melnikov; T Ecder; G Fantuzzi; B Siegmund; M S Lucia; C A Dinarello; R W Schrier; C L Edelstein Journal: J Clin Invest Date: 2001-05 Impact factor: 14.808
Authors: Lars Englberger; Rakesh M Suri; Zhuo Li; Edward T Casey; Richard C Daly; Joseph A Dearani; Hartzell V Schaff Journal: Crit Care Date: 2011-01-13 Impact factor: 9.097
Authors: Ryan M Whitaker; Midhun C Korrapati; Lindsey J Stallons; Sean R Jesinkey; John M Arthur; Craig C Beeson; Zhi Zhong; Rick G Schnellmann Journal: Toxicol Sci Date: 2015-02-09 Impact factor: 4.849
Authors: Jay L Koyner; Danielle L Davison; Ermira Brasha-Mitchell; Divya M Chalikonda; John M Arthur; Andrew D Shaw; James A Tumlin; Sharon A Trevino; Michael R Bennett; Paul L Kimmel; Michael G Seneff; Lakhmir S Chawla Journal: J Am Soc Nephrol Date: 2015-02-05 Impact factor: 10.121
Authors: Lodi C W Roksnoer; Bart F J Heijnen; Daisuke Nakano; Janos Peti-Peterdi; Stephen B Walsh; Ingrid M Garrelds; Jeanette M G van Gool; Robert Zietse; Harry A J Struijker-Boudier; Ewout J Hoorn; A H Jan Danser Journal: Hypertension Date: 2016-02-29 Impact factor: 10.190