-
Jay L Koyner,
Amit X Garg,
Michael G Shlipak,
Uptal D Patel, Kyaw Sint,
Kwangik Hong,
Prasad Devarajan,
Charles L Edelstein,
Michael Zappitelli,
Heather Thiessen-Philbrook,
Chirag R Parikh
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: 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. STUDY DESIGN: Prospective cohort study. SETTINGS & PARTICIPANTS: 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. INDEX TEST: Urinary CysC (in milligrams per liter) within the first 12 hours after surgery. OUTCOME: 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). OTHER MEASUREMENTS: 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. RESULTS: 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. LIMITATIONS: Limited numbers of patients with severe AKI and in-hospital dialysis treatment. CONCLUSIONS: Urinary CysC values are not associated significantly with the development of AKI after cardiac surgery in adults and children.
American Journal of Kidney Diseases 01/2013; · 5.43 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND AND OBJECTIVES: Preoperative proteinuria is associated with a higher incidence of postoperative AKI. Whether the same is true for postoperative proteinuria is uncertain. This study tested the hypothesis that increased proteinuria after cardiac surgery is associated with an increased risk for AKI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This prospective cohort study included 1198 adults undergoing cardiac surgery at six hospitals between July 2007 and December 2009. Albuminuria, urine albumin-to-creatinine ratio (ACR), and dipstick proteinuria were measured 0-6 hours after surgery. The primary outcome was AKI, defined as a doubling in serum creatinine or receipt of acute dialysis during the hospital stay. Analyses were adjusted for patient characteristics, including preoperative albuminuria. RESULTS: Compared with the lowest quintile, the highest quintile of albuminuria and highest grouping of dipstick proteinuria were associated with greatest risk for AKI (adjusted relative risks [RRs], 2.97 [95% confidence interval (CI), 1.20-6.91] and 2.46 [95% CI, 1.16-4.97], respectively). Higher ACR was not associated with AKI risk (highest quintile RR, 1.66 [95% CI, 0.68-3.90]). Of the three proteinuria measures, early postoperative albuminuria improved the prediction of AKI to the greatest degree (clinical model area under the curve, 0.75; 0.81 with albuminuria). Similar improvements with albuminuria were seen for net reclassification index (0.55; P<0.001) and integrated discrimination index (0.036; P<0.001). CONCLUSIONS: Higher levels of proteinuria after cardiac surgery identify patients at increased risk for AKI during their hospital stay.
Clinical Journal of the American Society of Nephrology 09/2012; · 5.23 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND AND OBJECTIVES: This study determined if preoperative and postoperative urine albumin/creatinine ratios (ACRs) predict postoperative AKI in children undergoing cardiac surgery (CS). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a three-center, prospective study (2007-2009) of 294 children undergoing CS (n=145 aged <2 years). Urine ACR was measured preoperatively and 0-6 hours after intensive care unit arrival. AKI outcomes were based on the Acute Kidney Injury Network serum creatinine (SCr) criteria (stage 1 AKI, ≥50% or 0.3 mg/dl SCr rise from baseline; and stage 2 or worse AKI, ≥SCr doubling or dialysis). AKI was predicted using preoperative and postoperative ACRs and postoperative ACR performance was compared with other AKI biomarkers. RESULTS: Preoperative ACR did not predict AKI in younger or older children. In children aged <2 years, first postoperative ACR ≥908 mg/g (103 mg/mmol) predicted stage 2 AKI development (adjusted relative risk, 3.4; 95% confidence interval, 1.2-9.4). In children aged ≥2 years, postoperative ACR ≥169 mg/g (19.1 mg/mmol) predicted stage 1 AKI (adjusted relative risk, 2.1; 95% confidence interval, 1.1-4.1). In children aged ≥2 years, first postoperative ACR improved AKI prediction from other biomarker and clinical prediction models, estimated by net reclassification improvement (P≤0.03), but only when serum cystatin C was also included in the model. CONCLUSIONS: Postoperative ACR is a readily available early diagnostic test for AKI after pediatric CS that performs similarly to other AKI biomarkers; however, its use is enhanced in children aged ≥2 years and in combination with serum cystatin C.
Clinical Journal of the American Society of Nephrology 08/2012; · 5.23 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: The 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 DESIGN: Prospective cohort study. SETTINGS & PARTICIPANTS: 1,150 high-risk adult cardiac surgery patients in the TRIBE-AKI (Translational Research Investigating Biomarker Endpoints for Acute Kidney Injury) Consortium. PREDICTOR: Changes in serum creatinine and cystatin C levels. OUTCOME: Postsurgical incidence of AKI. MEASUREMENTS: Serum 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. RESULTS: Overall, 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). LIMITATIONS: There were few adverse clinical outcomes, limiting our ability to detect differences in outcomes between subgroups of patients based on their definitions of AKI. CONCLUSIONS: In 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.
American Journal of Kidney Diseases 07/2012; · 5.43 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Being able to predict whether AKI will progress could improve monitoring and care, guide patient counseling, and assist with enrollment into trials of AKI treatment. Using samples from the Translational Research Investigating Biomarker Endpoints in AKI study (TRIBE-AKI), we evaluated whether kidney injury biomarkers measured at the time of first clinical diagnosis of early AKI after cardiac surgery can forecast AKI severity. Biomarkers included urinary IL-18, urinary albumin to creatinine ratio (ACR), and urinary and plasma neutrophil gelatinase-associated lipocalin (NGAL); each measurement was on the day of AKI diagnosis in 380 patients who developed at least AKI Network (AKIN) stage 1 AKI. The primary end point (progression of AKI defined by worsening AKIN stage) occurred in 45 (11.8%) patients. Using multivariable logistic regression, we determined the risk of AKI progression. After adjustment for clinical predictors, compared with biomarker values in the lowest two quintiles, the highest quintiles of three biomarkers remained associated with AKI progression: IL-18 (odds ratio=3.0, 95% confidence interval=1.3-7.3), ACR (odds ratio=3.4, 95% confidence interval=1.3-9.1), and plasma NGAL (odds ratio=7.7, 95% confidence interval=2.6-22.5). Each biomarker improved risk classification compared with the clinical model alone, with plasma NGAL performing the best (category-free net reclassification improvement of 0.69, P<0.0001). In conclusion, biomarkers measured on the day of AKI diagnosis improve risk stratification and identify patients at higher risk for progression of AKI and worse patient outcomes.
Journal of the American Society of Nephrology 03/2012; 23(5):905-14. · 9.66 Impact Factor
-
Uptal D Patel,
Amit X Garg,
Harlan M Krumholz,
Michael G Shlipak,
Steven G Coca, Kyaw Sint,
Heather Thiessen-Philbrook,
Jay L Koyner,
Madhav Swaminathan,
Cary S Passik,
Chirag R Parikh
[show abstract]
[hide abstract]
ABSTRACT: Acute kidney injury (AKI) after cardiac surgery is associated with poor outcomes and is difficult to predict. We conducted a prospective study to evaluate whether preoperative brain natriuretic peptide (BNP) levels predict postoperative AKI among patients undergoing cardiac surgery.
The Translational Research Investigating Biomarker Endpoints in Acute Kidney Injury (TRIBE-AKI) study enrolled 1139 adults undergoing cardiac surgery at 6 hospitals from 2007 to 2009 who were selected for high AKI risk. Preoperative BNP was categorized into quintiles. AKI was common with the use of Acute Kidney Injury Network definitions; at least mild AKI was a ≥0.3-mg/dL or 50% rise in creatinine (n=407, 36%), and severe AKI was either a doubling of creatinine or the requirement of acute renal replacement therapy (n=58, 5.1%). In analyses adjusted for preoperative characteristics, preoperative BNP was a strong and independent predictor of mild and severe AKI. Compared with the lowest BNP quintile, the highest quintile had significantly higher risk of at least mild AKI (risk ratio, 1.87; 95% confidence interval, 1.40-2.49) and severe AKI (risk ratio, 3.17; 95% confidence interval, 1.06-9.48). After adjustment for clinical predictors, the addition of BNP improved the area under the curve to predict at least mild AKI (0.67-0.69; P=0.02) and severe AKI (0.73-0.75; P=0.11). Compared with clinical parameters alone, BNP modestly improved risk prediction of AKI cases into lower and higher risk (continuous net reclassification index; at least mild AKI: risk ratio, 0.183; 95% confidence interval, 0.061-0.314; severe AKI: risk ratio, 0.231; 95% confidence interval, 0.067-0.506).
Preoperative BNP level is associated with postoperative AKI in high-risk patients undergoing cardiac surgery. If confirmed in other types of patients and surgeries, preoperative BNP may be a valuable component of future efforts to improve preoperative risk stratification and discrimination among surgical candidates.
Circulation 02/2012; 125(11):1347-55. · 14.74 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Acute kidney injury (AKI) duration after cardiac surgery is associated with poor survival in a dose-dependent manner. However, it is not known what perioperative risk factors contribute to prolonged AKI and delayed recovery. We sought to identify perioperative risk factors that predict duration of AKI, a complication that effects short and long-term survival.
We studied 4,987 consecutive cardiac surgery patients from 2002 through 2007. Acute kidney injury was defined as a 0.3 or greater (mg/dL) or 50% or greater increase in serum creatinine from baseline. Duration of AKI was defined by the number of days AKI was present. Stepwise multivariable negative binomial regression analysis was conducted using perioperative risk factors for AKI duration. The c-index was estimated by Kendall's tau.
Acute kidney injury developed in 39% of patients with a median duration of AKI at 3 days and ranged from 1 to 108 days. Patients without AKI had a duration of 0 days. Independent predictors of AKI duration included baseline patient and disease characteristics, and operative and postoperative factors. Prediction for mean duration of AKI was developed using coefficients from the regression model and externally validated the model on 1,219 cardiac surgery patients in a separate cardiac surgery cohort (Translational Research Investigating Biomarker Endpoints-AKI). The c-index was 0.65 (p<0.001) for the derivation cohort and 0.62 (p<0.001) for the validation cohort.
We identified and externally validated perioperative predictors of AKI duration. These risk factors will be useful to evaluate a patient's risk for the tempo of recovery from AKI after cardiac surgery and subsequent short and long-term survival. The levels of awareness created by working with these risk factors have implications regarding positive changes in processes of care that have the potential to decrease the incidence and mitigate AKI.
The Annals of thoracic surgery 12/2011; 93(2):570-6. · 3.74 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The study objective was to examine the utility of using proteinuria in preoperative risk stratification for acute kidney injury. Acute kidney injury is a common and important complication for patients undergoing cardiac surgery. Proteinuria, which reflects structural damage to the glomeruli or renal tubules, may aid the prediction of acute kidney injury.
The urine albumin to creatinine ratio and dipstick proteinuria concentration were prospectively measured in 1159 patients undergoing cardiac surgery. The cohort was organized into 4 clinical risk categories based on the preoperative urine albumin to creatinine ratio: 10 mg/g or less (≤ 1.1 mg/mmol), 11 to 29 mg/g (1.2-3.3 mg/mmol), 30 to 299 mg/g (3.4-33.8 mg/mmol), and 300 mg/g or greater (≥ 33.9 mg/mmol). The primary outcome was postoperative acute kidney injury, defined by the Acute Kidney Injury Network stage I criterion (serum creatinine increase ≥ 50% or ≥ 0.3 mg/dL; 26.5 μmol/L).
An increase in the incidence of acute kidney injury was noted across the urine albumin to creatinine ratio categories. Adding the urine albumin to creatinine ratio to the clinical model to predict acute kidney injury improved the area under the curve from 0.67 to 0.70 (P < .001), and the continuous net reclassification improvement was 29% (P < .001). The urine albumin to creatinine ratio was also independently associated with the risk of in-hospital dialysis and intensive care unit and hospital lengths of stay. Surgery status and preoperative glomerular filtration rate were effect modifiers; the association was stronger among those undergoing elective surgery and those with an estimated glomerular filtration rate of 45 mL/min/1.73 m(2) or greater.
Preoperative proteinuria provides graded stratification risk for acute kidney injury and is an independent predictor of other outcomes in patients undergoing cardiac surgery.
The Journal of thoracic and cardiovascular surgery 11/2011; 143(2):495-502. · 3.41 Impact Factor
-
Chirag R Parikh,
Prasad Devarajan,
Michael Zappitelli, Kyaw Sint,
Heather Thiessen-Philbrook,
Simon Li,
Richard W Kim,
Jay L Koyner,
Steven G Coca,
Charles L Edelstein,
Michael G Shlipak,
Amit X Garg,
Catherine D Krawczeski
[show abstract]
[hide abstract]
ABSTRACT: Acute kidney injury (AKI) occurs commonly after pediatric cardiac surgery and associates with poor outcomes. Biomarkers may help the prediction or early identification of AKI, potentially increasing opportunities for therapeutic interventions. Here, we conducted a prospective, multicenter cohort study involving 311 children undergoing surgery for congenital cardiac lesions to evaluate whether early postoperative measures of urine IL-18, urine neutrophil gelatinase-associated lipocalin (NGAL), or plasma NGAL could identify which patients would develop AKI and other adverse outcomes. Urine IL-18 and urine and plasma NGAL levels peaked within 6 hours after surgery. Severe AKI, defined by dialysis or doubling in serum creatinine during hospital stay, occurred in 53 participants at a median of 2 days after surgery. The first postoperative urine IL-18 and urine NGAL levels strongly associated with severe AKI. After multivariable adjustment, the highest quintiles of urine IL-18 and urine NGAL associated with 6.9- and 4.1-fold higher odds of AKI, respectively, compared with the lowest quintiles. Elevated urine IL-18 and urine NGAL levels associated with longer hospital stay, longer intensive care unit stay, and duration of mechanical ventilation. The accuracy of urine IL-18 and urine NGAL for diagnosis of severe AKI was moderate, with areas under the curve of 0.72 and 0.71, respectively. The addition of these urine biomarkers improved risk prediction over clinical models alone as measured by net reclassification improvement and integrated discrimination improvement. In conclusion, urine IL-18 and urine NGAL, but not plasma NGAL, associate with subsequent AKI and poor outcomes among children undergoing cardiac surgery.
Journal of the American Society of Nephrology 08/2011; 22(9):1737-47. · 9.66 Impact Factor
-
Michael Zappitelli,
Catherine D Krawczeski,
Prasad Devarajan,
Zhu Wang, Kyaw Sint,
Heather Thiessen-Philbrook,
Simon Li,
Michael R Bennett,
Qing Ma,
Michael G Shlipak,
Amit X Garg,
Chirag R Parikh
[show abstract]
[hide abstract]
ABSTRACT: In this multicenter, prospective study of 288 children (half under 2 years of age) undergoing cardiac surgery, we evaluated whether the measurement of pre- and postoperative serum cystatin C (CysC) improves the prediction of acute kidney injury (AKI) over that obtained by serum creatinine (SCr). Higher preoperative SCr-based estimated glomerular filtration rates predicted higher risk of the postoperative primary outcomes of stage 1 and 2 AKI (adjusted odds ratios (ORs) 1.5 and 1.9, respectively). Preoperative CysC was not associated with AKI. The highest quintile of postoperative (within 6 h) CysC predicted stage 1 and 2 AKI (adjusted ORs of 6 and 17.2, respectively). The highest tertile of percent change in CysC independently predicted AKI, whereas the highest tertile of SCr predicted stage 1 but not stage 2 AKI. Postoperative CysC levels independently predicted longer duration of ventilation and intensive care unit length of stay, whereas the postoperative SCr change only predicted longer intensive care unit stay. Thus, postoperative serum CysC is useful to risk-stratify patients for AKI treatment trials. More research, however, is needed to understand the relation between preoperative renal function and the risk of AKI.
Kidney International 04/2011; 80(6):655-62. · 6.61 Impact Factor
