Urinary biomarkers may provide prognostic information for subclinical acute kidney injury after cardiac surgery

Christian Albert, Annemarie Albert, Johanna Kube, Rinaldo Bellomo, Nicholas Wettersten, Hermann Kuppe, Sabine Westphal, Michael Haase, Anja Haase-Fielitz

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Objective: This study aimed to determine the biomarker-specific outcome patterns and short-and long-term prognosis of cardiac surgery–asoociated acute kidney injury (AKI) identified by standard criteria and/or urinary kidney biomarkers. Methods: Patients enrolled (N = 200), originated a German multicenter study (NCT00672334). Standard risk injury, failure, loss, and end-stage renal disease classification (RIFLE) criteria (including serum creatinine and urine output) and urinary kidney biomarker test result (neutrophil gelatinase-associated lipocalin, midkine, interleukin 6, and proteinuria) were used for diagnosis of postoperative AKI. Primary end point was acute renal replacement therapy or in-hospital mortality. Long-term end points among others included 5-year mortality. Patients with single-biomarker-positive subclinical AKI (RIFLE negative) were identified. We controlled for systemic inflammation using C-reactive protein test. Results: Urinary biomarkers (neutrophil gelatinase-associated lipocalin, midkine, and interleukin 6) were identified as independent predictors of the primary end point. Neutrophil gelatinase-associated lipocalin, midkine, or interleukin 6 positivity or de novo/worsening proteinuria identified 21.1%, 16.9%, 30.5%, and 48.0% more cases, respectively, with likely subclinical AKI (biomarker positive/RIFLE negative) additionally to cases with RIFLE positivity alone. Patients with likely subclinical AKI (neutrophil gelatinase-associated lipocalin or interleukin 6 positive) had increased risk of primary end point (adjusted hazard ratio, 7.18; 95% confidence interval, 1.52-33.93 [P =.013] and hazard ratio, 6.27; 95% confidence interval, 1.12-35.21 [P =.037]), respectively. Compared with biomarker-negative/RIFLE-positive patients, neutrophil gelatinase-associated lipocalin positive/RIFLE-positive or midkine-positive/RIFLE-positive patients had increased risk of primary end point (odds ratio, 9.6; 95% confidence interval, 1.4-67.3 [P =.033] and odds ratio, 14.7; 95% confidence interval, 2.0-109.2 [P =.011], respectively). Three percent to 11% of patients appear to be influenced by single-biomarker-positive subclinical AKI. During follow-up, kidney biomarker-defined short-term outcomes appeared to translate into long-term outcomes. Conclusions: Urinary kidney biomarkers identified RIFLE-negative patients with high-risk subclinical AKI as well as a higher risk subgroup of patients among RIFLE-AKI-positive patients. These findings support the concept that urinary biomarkers define subclinical AKI and higher risk subpopulations with worse long-term prognosis among standard patients with AKI.

Original languageEnglish
Pages (from-to)2441-2452.e13
Number of pages25
JournalJournal of Thoracic and Cardiovascular Surgery
Issue number6
Publication statusPublished - Jun 2018
Externally publishedYes


  • acute kidney injury
  • cardiac surgery
  • interleukin-6
  • midkine
  • neutrophil gelatinase-associated lipocalin
  • subclinical AKI

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