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Combining functional and tubular damage biomarkers improves diagnostic precision for acute kidney injury after cardiac surgery.

ABSTRACT: Increases in serum creatinine (?SCr) from baseline signify acute kidney injury (AKI) but offer little granular information regarding its characteristics. The 10th Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) suggested that combining AKI biomarkers would provide better precision for AKI course prognostication.This study investigated the value of combining a functional damage biomarker (plasma cystatin C [pCysC]) with a tubular damage biomarker (urine neutrophil gelatinase-associated lipocalin [uNGAL]), forming a composite biomarker for prediction of discrete characteristics of AKI.Data from 345 children after cardiopulmonary bypass (CPB) were analyzed. Severe AKI was defined as Kidney Disease Global Outcomes Initiative stages 2 to 3 (?100% ?SCr) within 7 days of CPB. Persistent AKI lasted >2 days. SCr in reversible AKI returned to baseline ?48 h after CPB. The composite of uNGAL (>200 ng/mg urine Cr = positive [+]) and pCysC (>0.8 mg/l = positive [+]), uNGAL+/pCysC+, measured 2 h after CPB initiation, was compared to ?SCr increases of ?50% for correlation with AKI characteristics by using predictive probabilities, likelihood ratios (LR), and area under the curve receiver operating curve (AUC-ROC) values [Corrected].Severe AKI occurred in 18% of patients. The composite uNGAL+/pCysC+ demonstrated a greater likelihood than ?SCr for severe AKI (+LR: 34.2 [13.0:94.0] vs. 3.8 [1.9:7.2]) and persistent AKI (+LR: 15.6 [8.8:27.5] versus 4.5 [2.3:8.8]). In AKI patients, the uNGAL-/pCysC+ composite was superior to ?SCr for prediction of transient AKI. Biomarker composites carried greater probability for specific outcomes than ?SCr strata.Composites of functional and tubular damage biomarkers are superior to ?SCr for predicting discrete characteristics of AKI.

SUBMITTER: Basu RK

PROVIDER: S-EPMC4310455 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Combining functional and tubular damage biomarkers improves diagnostic precision for acute kidney injury after cardiac surgery.

Basu Rajit K RK Wong Hector R HR Krawczeski Catherine D CD Wheeler Derek S DS Manning Peter B PB Chawla Lakhmir S LS Devarajan Prasad P Goldstein Stuart L SL

Journal of the American College of Cardiology 20141201 25

<h4>Background</h4>Increases in serum creatinine (ΔSCr) from baseline signify acute kidney injury (AKI) but offer little granular information regarding its characteristics. The 10th Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) suggested that combining AKI biomarkers would provide better precision for AKI course prognostication.<h4>Objectives</h4>This study investigated the value of combining a functional damage biomarker (plasma cystatin C [pCysC]) with a tubular damage b ...[more]

PMID: 25541128

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Project description:Background:Cardiac surgery-associated acute kidney injury (AKI) is associated with increased morbidity and mortality. We examined the utility of combining biomarkers of kidney function loss (serum cystatin C) and kidney tubular damage (urine neutrophil gelatinase-associated lipocalin [NGAL] and Kidney Injury Molecule-1 [KIM-1]) for the prediction of post-cardiac surgery AKI. Methods:Single-center prospective cohort study of 106 adults undergoing coronary artery bypass grafting and/or valve surgery with cardiopulmonary bypass (CPB). Primary outcome was postoperative in-hospital AKI defined by serum creatinine (SCr)-Kidney Disease: Improving Global Outcomes criteria. Biomarkers were measured preoperatively, 6 hours after CPB and on postoperative days (PODs) 1 to 4. Results:A total of 23 subjects (21.7%) developed AKI. After adjusting for preoperative left ventricular ejection fraction, body mass index >30 kg/m2, and estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2, the combination of peak serum cystatin C and peak urine KIM-1/creatinine (Cr) (6 hours post-CPB to POD 1) above optimal cutoff significantly associated with postoperative AKI (odds ratio [OR]: 5.32; 95% confidence interval [CI]: 1.31-21.67; P = 0.020). This biomarker combination significantly improved the performance of the clinical model for the prediction of postoperative AKI (area under the curve [AUC]: 0.77, 95% CI: 0.65-0.90 for the clinical model alone versus 0.83, 95% CI: 0.73-0.93 for the clinical model with the addition of biomarker data, P = 0.049). Conclusions:Combining biomarkers of postoperative kidney function loss and postoperative kidney tubular damage significantly improved prediction of in-hospital AKI following cardiac surgery. Future large, multicenter studies are warranted to assess whether panels of biomarkers reflecting distinct pathobiology can be used to guide interventions and improve short- and long-term outcomes in patients undergoing cardiac surgery.

Project description:RATIONALE & OBJECTIVE:Novel urinary biomarkers have enabled earlier detection of kidney tubular damage, but their prognostic value for adverse cardiovascular outcomes is uncertain. We hypothesized that tubular damage, measured by urine ?1-microglobulin (A1M), amino-terminal propeptide of type III procollagen (PIIINP), and neutrophil gelatinase-associated lipocalin (NGAL), would be associated with higher risks for cardiovascular events and mortality among elders. STUDY DESIGN:Case-cohort study. SETTING & PARTICIPANTS:This study included a randomly selected subcohort (n=502), cardiovascular disease (CVD) cases (n=245), and heart failure cases (n=220) from the Health, Aging, and Body Composition (Health ABC) Study. PREDICTORS:Baseline urine A1M, PIIINP, and NGAL concentrations. OUTCOMES:Incident CVD, heart failure, and all-cause mortality. ANALYTICAL APPROACH:Cox proportional hazards models were used to evaluate biomarker associations with each outcome. RESULTS:At baseline, mean age was 74 years and estimated glomerular filtration rate was 73mL/min/1.73m2. After adjustment for demographics, estimated glomerular filtration rate, albumin-creatinine ratio, and other cardiovascular risk factors, each doubling in biomarker concentration was associated with the following adjusted HRs for CVD: A1M, 1.51 (95% CI, 1.16-1.96); PIIINP, 1.21 (95% CI, 1.00-1.46); and NGAL, 1.12 (95% CI, 1.05-1.20). There were 248 deaths in the subcohort during a median follow-up of 12.4 years. Adjusted associations of each biomarker (HR per doubling) with all-cause mortality were: A1M, 1.29 (95% CI, 1.10-1.51); PIIINP, 1.05 (95%, 0.94-1.18); and NGAL, 1.07 (95% CI, 1.02-1.12). Biomarker concentrations did not have statistically significant associations with heart failure after multivariable adjustment. LIMITATIONS:Urine biomarkers were measured at a single time point; no validation cohort available. CONCLUSIONS:Kidney tubular damage is an independent risk factor for CVD and death among elders. Future studies should investigate mechanisms by which kidney tubular damage may adversely affect cardiovascular risk.

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Combining functional and tubular damage biomarkers improves diagnostic precision for acute kidney injury after cardiac surgery.

Publications

Combining functional and tubular damage biomarkers improves diagnostic precision for acute kidney injury after cardiac surgery.

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