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Urinary cystatin C and acute kidney injury after cardiac surgery.

ABSTRACT: Acute kidney injury (AKI) is common after cardiac surgery and is associated with adverse patient outcomes. Urinary cystatin C (CysC) level is a biomarker of proximal tubule function and may increase earlier in AKI than serum creatinine level.Prospective cohort study.The TRIBE AKI (Translational Research Investigating Biomarker Endpoints in AKI) Consortium prospectively enrolled 1,203 adults and 299 children and adolescents at 8 institutions in 2007-2009.Urinary CysC (in milligrams per liter) within the first 12 hours after surgery.Serum creatinine-based AKI was defined as AKI Network stage 1 (mild AKI) and doubling of serum creatinine from the preoperative value or need for dialysis during hospitalization (severe AKI).Analyses were adjusted for characteristics used clinically for AKI risk stratification, including age, sex, race, estimated glomerular filtration rate, diabetes, hypertension, heart failure, nonelective surgery, cardiac catheterization within 72 hours, type of surgery, myocardial infarction, and cardiopulmonary bypass time longer than 120 minutes.Urinary CysC level measured in the early postoperative period (0-6 and 6-12 hours postoperatively) correlated with both mild and severe AKI in adults and children. However, after analyses were adjusted for other factors, the effect was attenuated for both forms of AKI in both cohorts.Limited numbers of patients with severe AKI and in-hospital dialysis treatment.Urinary CysC values are not associated significantly with the development of AKI after cardiac surgery in adults and children.

SUBMITTER: Koyner JL

PROVIDER: S-EPMC3627833 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Urinary cystatin C and acute kidney injury after cardiac surgery.

Koyner Jay L JL Garg Amit X AX Shlipak Michael G MG Patel Uptal D UD Sint Kyaw K Hong Kwangik K Devarajan Prasad P Edelstein Charles L CL Zappitelli Michael M Thiessen-Philbrook Heather H Parikh Chirag R CR

American journal of kidney diseases : the official journal of the National Kidney Foundation 20130116 5

<h4>Background</h4>Acute kidney injury (AKI) is common after cardiac surgery and is associated with adverse patient outcomes. Urinary cystatin C (CysC) level is a biomarker of proximal tubule function and may increase earlier in AKI than serum creatinine level.<h4>Study design</h4>Prospective cohort study.<h4>Settings & participants</h4>The TRIBE AKI (Translational Research Investigating Biomarker Endpoints in AKI) Consortium prospectively enrolled 1,203 adults and 299 children and adolescents a ...[more]

PMID: 23332602

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Project description:BackgroundAcute kidney injury (AKI) after cardiac surgery is associated with poor outcomes, but is challenging to predict from information available before surgery.Study designProspective cohort study.Setting & participantsThe TRIBE-AKI (Translational Research Investigating Biomarker Endpoints in Acute Kidney Injury) Consortium enrolled 1,147 adults undergoing cardiac surgery at 6 hospitals from 2007-2009; participants were selected for high AKI risk.PredictorsPresurgical values for cystatin C, creatinine, and creatinine-based estimated glomerular filtration rate (eGFR) were categorized into quintiles and grouped as "best" (quintiles 1-2), "intermediate" (quintiles 3-4), and "worst" (quintile 5) kidney function.OutcomesThe primary outcome was AKI Network (AKIN) stage 1 or higher; ≥0.3 mg/dL or 50% increase in creatinine level.MeasurementsAnalyses were adjusted for characteristics used clinically for presurgical risk stratification.ResultsAverage age was 71 ± 10 years (mean ± standard deviation); serum creatinine, 1.1 ± 0.3 mg/dL; eGFR-Cr, 74 ± 9 mL/min/1.73 m(2); and cystatin C, 0.9 ± 0.3 mg/L. 407 (36%) participants developed AKI during hospitalization. Adjusted odds ratios for intermediate and worst kidney function by cystatin C were 1.9 (95% CI, 1.4-2.7) and 4.8 (95% CI, 2.9-7.7) compared with 1.2 (95% CI, 0.9-1.7) and 1.8 (95% CI, 1.2-2.6) for creatinine and 1.0 (95% CI, 0.7-1.4) and 1.7 (95% CI, 1.1-2.3) for eGFR-Cr categories, respectively. After adjustment for clinical predictors, the C statistic to predict AKI was 0.70 without kidney markers, 0.69 with creatinine, and 0.72 with cystatin C. Cystatin C also substantially improved AKI risk classification compared with creatinine, based on a net reclassification index of 0.21 (P < 0.001).LimitationsThe ability of these kidney biomarkers to predict risk of dialysis-requiring AKI or death could not be assessed reliably in our study because of a small number of patients with either outcome.ConclusionsPresurgical cystatin C is better than creatinine or creatinine-based eGFR at forecasting the risk of AKI after cardiac surgery.

Project description:Objectives: Secretion of extracellular vesicles (EV) and associated micro-RNAs (miR) is altered during cellular stress and may serve as biomarkers of organ injury. We hypothesized that measuring changes in urinary levels of EV and miR will predict the onset of acute kidney injury in cardiac surgery patients. Design: Predictive accuracy biomarker study performed in the cohort of the REVAKI-2 trial Setting: Single center ICU between September 2015 and September 2018 Interventions: Intravenous sildenafil citrate 12.5 mg kg-1 over 150 min or dextrose 5% at the commencement of surgery. Measurements and main results: Urine samples were collected before and 24 hours after the procedure from 93 cardiac surgery patients. Urine EV concentrations and size distribution were assessed using NanoSight. EV derivation and levels were measured using flow cytometry. Samples from 10 selected patients were sequenced to detect differentially expressed miR. Verification was performed with advanced TaqMan assays in samples from all patients. Urine EV concentrations significantly increased in patients with AKI after surgery, with the percentage of EV positive for aquaporin-2 and β1-integrin also increasing. Pre surgery podocalyxin-positive EV were significantly lower, and β1-integrin EV werehigher in patients with AKI. The levels of the former correlated with the severity of theinjury. miR-125a-5p was expressed at higher levels in urine from patients with AKI stage 2/3. Levels of miR-10a-5p decreased after surgery in AKI patients; its levels correlated with the severity of the injury. Preoperative levels of podocalyxin EVs and miR-125a-5p had moderate AKI predictive value and, in a logistic model together with ICU lactate levels, offered good (AUC = 80.9%) AKI prediction. Conclusions: Lower levels of podocalyxin-positive EV at baseline predict the severity of post-surgery AKI. Urine EV concentrations and miR expression offer excellent predictive accuracy when combined with commonly measured biomarkers.

Project description:BackgroundThe primary aim of this study was to compare the sensitivity and rapidity of acute kidney injury (AKI) detection by cystatin C level relative to creatinine level after cardiac surgery.Study designProspective cohort study.Settings & participants1,150 high-risk adult cardiac surgery patients in the TRIBE-AKI (Translational Research Investigating Biomarker Endpoints for Acute Kidney Injury) Consortium.PredictorChanges in serum creatinine and cystatin C levels.OutcomePostsurgical incidence of AKI.MeasurementsSerum creatinine and cystatin C were measured at the preoperative visit and daily on postoperative days 1-5. To allow comparisons between changes in creatinine and cystatin C levels, AKI end points were defined by the relative increases in each marker from baseline (25%, 50%, and 100%) and the incidence of AKI was compared based on each marker. Secondary aims were to compare clinical outcomes among patients defined as having AKI by cystatin C and/or creatinine levels.ResultsOverall, serum creatinine level detected more cases of AKI than cystatin C level: 35% developed a ≥25% increase in serum creatinine level, whereas only 23% had a ≥25% increase in cystatin C level (P < 0.001). Creatinine level also had higher proportions meeting the 50% (14% and 8%; P < 0.001) and 100% (4% and 2%; P = 0.005) thresholds for AKI diagnosis. Clinical outcomes generally were not statistically different for AKI cases detected by creatinine or cystatin C level. However, for each AKI threshold, patients with AKI confirmed by both markers had a significantly higher risk of the combined mortality/dialysis outcome compared with patients with AKI detected by creatinine level alone (P = 0.002).LimitationsThere were few adverse clinical outcomes, limiting our ability to detect differences in outcomes between subgroups of patients based on their definitions of AKI.ConclusionsIn this large multicenter study, we found that cystatin C level was less sensitive for AKI detection than creatinine level. However, confirmation by cystatin C level appeared to identify a subset of patients with AKI with a substantially higher risk of adverse outcomes.

Project description:BackgroundAcute kidney injury (AKI) following cardiac surgery leads to increased morbidity and mortality. Characterization and validation of early biomarkers of AKI may ultimately facilitate early therapeutic intervention. We have previously identified that elevated urinary hepcidin-25 is inversely and independently associated with the development of AKI in adult cardiac surgery patients. Hepcidin-25 is an antimicrobial peptide that sequesters iron intracellularly, and its elevation following human ischemia reperfusion injury may represent a renoprotective response to minimize renal injury.ObjectiveOur goal was to validate urinary hepcidin-25 as a non-invasive biomarker in an independent cardiac surgery cohort, within the context of clinical AKI predictors.DesignProspective observational cohort study.SettingAdult cardiac surgery program at St. Boniface Hospital, Winnipeg, Manitoba, Canada.PatientsAdult cardiac surgery patients undergoing cardiopulmonary bypass (CPB), n = 306.MeasurementsUrine hepcidin-25, measured on post-operative day (POD) 1.MethodsA prospective, observational cohort of adult CPB patients (n = 306) was collected with serial perioperative urine samples. Urine hepcidin-25 at POD 1 was measured by competitive ELISA. Its diagnostic performance was evaluated in conjunction with clinical parameters and the Thakar clinical prediction score, using multivariate logistic regression.ResultsUrinary hepcidin-25 is elevated following cardiac surgery in AKI and non-AKI patients. Elevated urinary hepcidin-25 concentration was inversely associated with AKI on both univariate (odds ratio [OR]: 0.61, 95% confidence interval [CI]: 0.45-0.83, P = .002) and multivariate analysis (OR: 0.67, 95% CI: 0.50-0.95, P = .02). A combined model with clinical risk factors demonstrated that baseline estimated glomerular filtration rate (eGFR), diabetes mellitus, and urinary hepcidin-25 concentration had an overall area under the curve (AUC) of 0.82 (0.75-0.88) for predicting subsequent AKI development, which was superior to clinical prediction alone as determined by the Thakar score.Limitations(1) A single-center observational study. (2) Polyclonal antibody-based competitive ELISA.ConclusionHepcidin-25 is inversely associated with AKI in a multivariate model when combined with eGFR and diabetes mellitus, with an overall AUC of 0.82. Notably, urinary hepcidin-25 improves on clinical AKI prediction compared to the Thakar score alone.

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Urinary cystatin C and acute kidney injury after cardiac surgery.

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Urinary cystatin C and acute kidney injury after cardiac surgery.

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