Urinary Biomarkers of AKI and Mortality 3 Years after Cardiac Surgery

Coca, Steven G.; Garg, Amit X.; Thiessen-Philbrook, Heather; Koyner, Jay L.; Patel, Uptal D.; Krumholz, Harlan M.; Shlipak, Michael G.; Parikh, Chirag R.

doi:10.1681/asn.2013070742

Cited by 154 publications

(144 citation statements)

References 28 publications

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“…Before surgery, for example, we had already observed significant differences in IL-6 among patients who went on to develop both AKI and severe AKI. Our findings build on our previous work that has provided both diagnostic and prognostic information for clinical prediction models [26][27][28][29][30][31][32][33][34] and demonstrates that these cytokines may serve as prognostic biomarkers for perioperative outcomes.…”

Section: Discussionsupporting

confidence: 81%

Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery

Zhang

Garg

Coca

et al. 2015

Journal of the American Society of Nephrology

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176

119

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Inflammation has an integral role in the pathophysiology of AKI. We investigated the associations of two biomarkers of inflammation, plasma IL-6 and IL-10, with AKI and mortality in adults undergoing cardiac surgery. Patients were enrolled at six academic centers (n=960). AKI was defined as a $50% or $0.3-mg/dl increase in serum creatinine from baseline. Pre-and postoperative IL-6 and IL-10 concentrations were categorized into tertiles and evaluated for associations with outcomes of in-hospital AKI or postdischarge all-cause mortality at a median of 3 years after surgery. Preoperative concentrations of IL-6 and IL-10 were not significantly associated with AKI or mortality. Elevated first postoperative IL-6 concentration was significantly associated with higher risk of AKI, and the risk increased in a dose-dependent manner (second tertile adjusted odds ratio [OR], 1.61 [95% confidence interval (95% CI), 1.10 to 2.36]; third tertile adjusted OR, 2.13 [95% CI, 1.45 to 3.13]). First postoperative IL-6 concentration was not associated with risk of mortality; however, the second tertile of peak IL-6 concentration was significantly associated with lower risk of mortality (adjusted hazard ratio, 0.75 [95% CI, 0.57 to 0.99]). Elevated first postoperative IL-10 concentration was significantly associated with higher risk of AKI (adjusted OR, 1.57 [95% CI, 1.04 to 2.38]) and lower risk of mortality (adjusted HR, 0.72 [95% CI, 0.56 to 0.93]). There was a significant interaction between the concentration of neutrophil gelatinase-associated lipocalin, an established AKI biomarker, and the association of IL-10 concentration with mortality (P=0.01). These findings suggest plasma IL-6 and IL-10 may serve as biomarkers for perioperative outcomes. AKI is a common complication of cardiac surgery, leading to increased morbidity and mortality. 1 Current paradigms of diagnosis and treatment are based on serum creatinine and are thus insensitive. These limitations have spurred the search for novel proteins that are involved in the process of kidney injury. 2,3 While AKI is traditionally recognized and diagnosed by renal functional impairment and structural damage, it is also an inflammatory condition. Understanding and measuring the processes of inflammation in AKI may provide unique tools for its assessment and prediction.To this end, we developed an ancillary study to our large, multicenter cohort study of adult patients

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Section: Discussionsupporting

confidence: 81%

Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery

Zhang

Garg

Coca

et al. 2015

Journal of the American Society of Nephrology

Self Cite

176

119

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“…Recently, Coca et al 1 showed that several biomarkers of AKI measured in the perioperative period after adult cardiothoracic surgery correlated with long-term risk of mortality. In their follow-up of 1199 adults from the Translational Research Investigating Biomarker Endpoints in Acute Kidney Injury (TRIBE-AKI) cohort, Coca et al 1 showed that, compared with the first tertiles, the third tertiles of peak biomarker percentages of urine neutrophil gelatinase associated lipocalin, interleukin-18, kidney injury molecule-1, liver fatty acid binding protein, and urine albumin were all associated with a significantly increased risk of mortality in those subjects who developed postoperative AKI.…”

Section: Risk Of Death or Dialysis Increased Atmentioning

confidence: 99%

“…[1][2][3][4][5][6][7] Over the last decade, there has been intense investigation of biomarkers of kidney injury in an attempt to complement and augment the diagnostic abilities of current measures of kidney function. 8 To date, little is known about the relationship between these novel biomarkers and long-term outcomes, 9,10 with only one largescale multicenter investigation linking some biomarkers collected around the time of AKI with long-term mortality.…”

mentioning

confidence: 99%

“…8 To date, little is known about the relationship between these novel biomarkers and long-term outcomes, 9,10 with only one largescale multicenter investigation linking some biomarkers collected around the time of AKI with long-term mortality. 1 We have recently published the results of a prospective, observational international investigation (the Sapphire study) of tissue inhibitor metalloprotease-2 (TIMP-2) and IGF-binding protein 7 (IGFBP7; both markers of G1 cell cycle arrest) in the setting of critical illness. 10 Subsequently, we validated two [TIMP-2]z[IGFBP7] cutoffs for risk assessment for development of AKI.…”

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confidence: 99%

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Tissue Inhibitor Metalloproteinase-2 (TIMP-2)⋅IGF-Binding Protein-7 (IGFBP7) Levels Are Associated with Adverse Long-Term Outcomes in Patients with AKI

Koyner

Shaw

Chawla³

et al. 2015

Journal of the American Society of Nephrology

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211

142

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Tissue inhibitor metalloproteinase-2 (TIMP-2) and IGF-binding protein-7 (IGFBP7) have been validated for risk stratification in AKI. However, the association of urinary TIMP-2 and IGFBP7 with longterm outcomes is unknown. We evaluated the 9-month incidence of a composite end point of all-cause mortality or the need for RRT in a secondary analysis of a prospective observational international study of critically ill adults. Two predefined [TIMP-2]z[IGFBP7] cutoffs (0.3 for high sensitivity and 2.0 for high specificity) for the development of AKI were evaluated. Cox proportional hazards models were used to determine risk for the composite end point. Baseline

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“…These datasets were linked using unique encoded identifiers and analyzed at the Institute for Clinical Evaluative Sciences (ICES). Full study details were previously described 34, 35, 36…”

Section: Methodsmentioning

confidence: 99%

Predictive Ability of Novel Cardiac Biomarkers ST2, Galectin‐3, and NT‐ProBNP Before Cardiac Surgery

Polineni

Parker

Alam

et al. 2018

JAHA

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BackgroundCurrent preoperative models use clinical risk factors alone in estimating risk of in‐hospital mortality following cardiac surgery. However, novel biomarkers now exist to potentially improve preoperative prediction models. An assessment of Galectin‐3, N‐terminal pro b‐type natriuretic peptide (NT‐ProBNP), and soluble ST2 to improve the predictive ability of an existing prediction model of in‐hospital mortality may improve our capacity to risk‐stratify patients before surgery.Methods and ResultsWe measured preoperative biomarkers in the NNECDSG (Northern New England Cardiovascular Disease Study Group), a prospective cohort of 1554 patients undergoing coronary artery bypass graft surgery. Exposures of interest were preoperative levels of galectin‐3, NT‐ProBNP, and ST2. In‐hospital mortality and adverse events occurring after coronary artery bypass graft were the outcomes. After adjustment, NT‐ProBNP and ST2 showed a statistically significant association with both their median and third tercile categories with NT‐ProBNP odds ratios of 2.89 (95% confidence interval [CI]: 1.04–8.05) and 5.43 (95% CI: 1.21–24.44) and ST2 odds ratios of 3.96 (95% CI: 1.60–9.82) and 3.21 (95% CI: 1.17–8.80), respectively. The model receiver operating characteristic score of the base prediction model (0.80 [95% CI: 0.72–0.89]) varied significantly from the new multi‐marker model (0.85 [95% CI: 0.79–0.91]). Compared with the Northern New England (NNE) model alone, the full prediction model with biomarkers NT‐proBNP and ST2 shows significant improvement in model classification of in‐hospital mortality.ConclusionsThis study demonstrates a significant improvement of preoperative prediction of in‐hospital mortality in patients undergoing coronary artery bypass graft and suggests that biomarkers can be used to identify patients at higher risk.

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Urinary Biomarkers of AKI and Mortality 3 Years after Cardiac Surgery

Cited by 154 publications

References 28 publications

Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery

Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery

Tissue Inhibitor Metalloproteinase-2 (TIMP-2)⋅IGF-Binding Protein-7 (IGFBP7) Levels Are Associated with Adverse Long-Term Outcomes in Patients with AKI

Predictive Ability of Novel Cardiac Biomarkers ST2, Galectin‐3, and NT‐ProBNP Before Cardiac Surgery

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