[Show abstract][Hide abstract] ABSTRACT: Reviewing the literature in many fields on proposed risk models reveals problems with the way many risk models are developed. Furthermore, papers reporting new risk models do not always provide sufficient information to allow readers to assess the merits of the model. In this review, we discuss sources of bias that can arise in risk model development. We focus on two biases that can be introduced during data analysis. These two sources of bias are sometimes conflated in the literature and we recommend the terms resubstitution bias and model-selection bias to delineate them. We also propose the RiGoR reporting standard to improve transparency and clarity of published papers proposing new risk models.
[Show abstract][Hide abstract] ABSTRACT: Higher levels of plasma neutrophil gelatinase-associated lipocalin (pNGAL) are an early marker of acute kidney injury and are associated with increased risk of short-term adverse outcomes. The independent association between pNGAL and long-term mortality is unknown.
In this prospective observational cohort study, we studied 1191 adults who underwent cardiac surgery between 2007 and 2009 at 6 centers in the TRIBE-AKI cohort. We measured the pNGAL on the pre-operative and first 3 post-operative days and assessed the relationship of peri-operative pNGAL concentrations with all-cause mortality.
During a median follow-up of 3.0 years, 139 participants died (50/1000 person-years). Pre-operative levels of pNGAL were associated with 3-year mortality (unadjusted HR 1.96, 95% CI 1.34,2.85) and the association persisted after adjustment for pre-operative variables including estimated glomerular filtration rate (adjusted HR 1.48, 95% CI 1.04-2.12). After adjustment for pre- and intra-operative variables, including pre-operative NGAL levels, the highest tertiles of first post-operative and peak post-operative pNGAL were also independently associated with 3-year mortality risk (adjusted HR 1.31, 95% CI 1.0-1.7 and adjusted HR 1.78, 95% CI 1.2-2.7, respectively). However, after adjustment for peri-operative changes in serum creatinine, there was no longer an independent association between the first post-operative and peak post-operative pNGAL and long-term mortality (adjusted HR 0.98,95% CI 0.79-1.2 for first pNGAL and adjusted HR 1.19, 95% CI 0.87-1.61 for peak pNGAL).
Pre-operative pNGAL levels were independently associated with 3-year mortality after cardiac surgery. While post-operative pNGAL levels were also associated with 3-year mortality, this relationship was not independent of changes in serum creatinine. These findings suggest that while pre-operative pNGAL adds prognostic value for mortality beyond routinely available serum creatinine, post-operative pNGAL measurements may not be as useful for this purpose.
PLoS ONE 06/2015; 10(6):e0129619. DOI:10.1371/journal.pone.0129619 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Children undergoing cardiac surgery may exhibit a pronounced inflammatory response to cardiopulmonary bypass (CPB). Inflammation is recognized as an important pathophysiologic process leading to acute kidney injury (AKI). The aim of this study was to evaluate the association of the inflammatory cytokines interleukin (IL)-6 and IL-10 with AKI and other adverse outcomes in children after CPB surgery.
This is a sub-study of the Translational Research Investigating Biomarker Endpoints in AKI (TRIBE-AKI) cohort, including 106 children ranging in age from 1 month to 18 years undergoing CPB. Plasma IL-6 and IL-10 concentrations were measured preoperatively and postoperatively [day 1 (within 6 h after surgery) and day 3].
Stage 2/3 AKI, defined by at least a doubling of the baseline serum creatinine concentration or dialysis, was diagnosed in 24 (23 %) patients. The preoperative IL-6 concentration was significantly higher in patients with stage 2/3 AKI [median 2.6 pg/mL, interquartile range (IQR) 2.6 0.6-4.9 pg/mL] than in those without stage 2/3 AKI (median 0.6 pg/mL, IQR 0.6-2.2 pg/mL) (p = 0.03). After adjustment for clinical and demographic variables, the highest preoperative IL-6 tertile was associated with a sixfold increased risk for stage 2/3 AKI compared with the lowest tertile (adjusted odds ratio 6.41, 95 % confidence interval 1.16-35.35). IL-6 and IL-10 levels increased significantly after surgery, peaking postoperatively on day 1. First postoperative IL-6 and IL-10 measurements did not significantly differ between patients with stage 2/3 AKI and those without stage 2/3 AKI. The elevated IL-6 level on day 3 was associated with longer hospital stay (p = 0.0001).
Preoperative plasma IL-6 concentration is associated with the development of stage 2/3 AKI and may be prognostic of resource utilization.
[Show abstract][Hide abstract] ABSTRACT: Research has identified improved biomarkers of acute kidney injury (AKI). Cystatin C (CysC) is a better glomerular filtration rate marker than serum creatinine (SCr) and may improve AKI definition.
To determine if defining clinical AKI by increases in CysC vs SCr alters associations with biomarkers and clinical outcomes.
Three-center prospective cohort study of intensive care units in New Haven, Connecticut, Cincinnati, Ohio, and Montreal, Quebec, Canada. Participants were 287 patients 18 years or younger without preoperative AKI or end-stage renal disease who were undergoing cardiac surgery. The study dates were July 1, 2007, through December 31, 2009.
For biomarker vs clinical AKI associations, the exposures were first postoperative (0-6 hours after surgery) urine interleukin 18, neutrophil gelatinase-associated lipocalin, kidney injury molecule 1, and liver fatty acid-binding protein. For clinical AKI outcome associations, the exposure was Kidney Disease: Improving Global Outcomes AKI definition (based on SCr or CysC).
Clinical AKI, length of stay, and length of mechanical ventilation. We determined areas under the receiver operating characteristic curve and odds ratios for first postoperative biomarkers to predict AKI.
The SCr-defined vs CysC-defined AKI incidence differed substantially (43.6% vs 20.6%). Percentage agreement was 71% (κ = 0.38); stage 2 or worse AKI percentage agreement was 95%. Interleukin 18 and kidney injury molecule 1 discriminated for CysC-defined AKI better than for SCr-defined AKI. For interleukin 18 and kidney injury molecule 1, the areas under the receiver operating characteristic curve were 0.74 and 0.65, respectively, for CysC-defined AKI, and 0.66 and 0.58, respectively, for SCr-defined AKI. Fifth (vs first) quintile concentrations of both biomarkers were more strongly associated with CysC-defined AKI. For interleukin 18 and kidney injury molecule 1, the odds ratios were 16.19 (95% CI, 3.55-73.93) and 6.93 (95% CI, 1.88-25.59), respectively, for CysC-defined AKI vs 6.60 (95% CI, 2.76-15.76) and 2.04 (95% CI, 0.94-4.38), respectively, for SCr-defined AKI. Neutrophil gelatinase-associated lipocalin and liver fatty acid-binding protein associations with both definitions were similar. The CysC definitions and SCr definitions were similarly associated with clinical outcomes of resource use.
Compared with the SCr-based definition, the CysC-based definition is more strongly associated with urine interleukin 18 and kidney injury molecule 1 in children undergoing cardiac surgery. Consideration should be made for defining AKI based on CysC in clinical care and future studies.
[Show abstract][Hide abstract] ABSTRACT: AKI is a common and severe complication in patients with cirrhosis. AKI progression was previously shown to correlate with in-hospital mortality. Therefore, accurately predicting which patients are at highest risk for AKI progression may allow more rapid and targeted treatment. Urinary biomarkers of structural kidney injury associate with AKI progression and mortality in multiple settings of AKI but their prognostic performance in patients with liver cirrhosis is not well known.
Clinical Journal of the American Society of Nephrology 09/2014; 9(11). DOI:10.2215/CJN.09430913 · 5.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Adjudication of patient outcomes is a common practice in medical research and clinical trials. However minimal data exists on the adjudication process in the setting of Acute Kidney Injury (AKI) as well as the ability to judge different etiologies (e.g. Acute Tubular Necrosis (ATN), Pre-renal Azotemia (PRA)).
We enrolled 475 consecutive patients undergoing cardiac surgery at four sites of the Translational Research Investigating Biomarker Endpoints in AKI (TRIBE-AKI) study. Three expert nephrologists performed independent chart review, utilizing clinical variables and retrospective case report forms with pre intra and post-operative data, and then adjudicated all cases of AKI (n = 67). AKI was defined as a > 50% increase in serum creatinine for baseline (RIFLE Risk). We examined the patterns of AKI diagnoses made by the adjudication panel as well as association of these diagnoses with pre and postoperative kidney injury biomarkers.
There was poor agreement across the panel of reviewers with their adjudicated diagnoses being independent of each other (Fleiss’ Kappa = 0.046). Based on the agreement of the two out of three reviewers, ATN was the adjudicated diagnosis in 41 cases (61%) while PRA occurred in 13 (19%). Neither serum creatinine or any other biomarker of AKI (urine or serum), was associated with an adjudicated diagnosis of ATN within the first 24 post-operative hours.
The etiology of AKI after cardiac surgery is probably multi-factorial and pure forms of AKI etiologies, such as ATN and PRA may not exist. Biomarkers did not appear to correlate with the adjudicated etiology of AKI; however the lack of agreement among the adjudicators impacted these results.
[Show abstract][Hide abstract] ABSTRACT: The field of nephrology is actively involved in developing biomarkers and improving models for predicting patients' risks of AKI and CKD and their outcomes. However, some important aspects of evaluating biomarkers and risk models are not widely appreciated, and statistical methods are still evolving. This review describes some of the most important statistical concepts for this area of research and identifies common pitfalls. Particular attention is paid to metrics proposed within the last 5 years for quantifying the incremental predictive value of a new biomarker.
Clinical Journal of the American Society of Nephrology 05/2014; 9(8). DOI:10.2215/CJN.10351013 · 5.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Interest in developing and using novel markers of kidney injury is increasing. To maintain scientific rigour in these endeavors, a comprehensive understanding of statistical methodology is required to rigorously assess the incremental value of novel biomarkers in existing clinical risk prediction models. Such knowledge is especially relevant, because no single statistical method is sufficient to evaluate a novel biomarker. In this review, we highlight the strengths and limitations of various traditional and novel statistical methods used in the literature for biomarker studies and use biomarkers of AKI as examples to show limitations of some popular statistical methods.
Journal of the American Society of Nephrology 05/2014; 25(8). DOI:10.1681/ASN.2013121300 · 9.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acute kidney injury (AKI) is a serious complication of cardiac operations for which there remains no specific therapy. Animal data and several observational studies suggest that statins prevent AKI, but the results are not conclusive, and many studies are retrospective in nature.
We conducted a multicenter prospective cohort study of 625 adult patients undergoing elective cardiac operations. All patients were taking statins and were grouped according to whether statins were continued or held in the 24 hours before operation. The primary outcome was AKI as defined by a doubling of serum creatinine or dialysis. The secondary outcome was the peak level of several kidney injury biomarkers. The results were adjusted for demographic and clinical factors.
Continuing (vs holding) a statin before operation was not associated with a lower risk of AKI, as defined by a doubling of serum creatinine or dialysis (adjusted relative risk [RR] 1.09; 95% confidence interval [CI] 0.44, 2.70). However, continuing a statin was associated with a lower risk of elevation of the following AKI biomarkers: urine interleukin-18, urine neutrophil gelatinase-associated lipocalin, urine kidney injury molecule-1, and plasma neutrophil gelatinase-associated lipocalin (adjusted RR 0.34; 95% CI 0.18, 0.62), (adjusted RR 0.41; 95% CI 0.22, 0.76), (adjusted RR 0.37; 95% CI 0.20, 0.76), (adjusted RR 0.62; 95% CI 0.39, 0.98), respectively.
Statins may prevent kidney injury after cardiac operations, as evidenced by lower levels of kidney injury biomarkers.
The Annals of thoracic surgery 04/2014; 97(6). DOI:10.1016/j.athoracsur.2014.02.033 · 3.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acute kidney injury (AKI) after pediatric cardiac operations 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 children undergoing cardiac operations.
This was a three-center, prospective study (2007-2009) of 277 children undergoing cardiac operations (n = 121, aged <2 years) with available preoperative BNP values. Preoperative BNP was measured and categorized into tertiles. The performance of BNP was evaluated alone and in combination with clinical factors. AKI was defined as doubling of serum creatinine or need for acute dialysis.
Postoperative AKI occurred in 165 children (60%), with 118 cases (43%) being mild and 47 cases (17%) severe. Preoperative BNP was not associated with increased risk of mild or severe postoperative AKI and did not significantly improve AKI risk prediction when added to clinical models. Preoperative BNP was, however, associated with several clinical outcomes, including length of stay and mechanical ventilation. The results were similar when the analysis was repeated in the subset of children younger than 2 years of age or when the association of postoperative BNP and AKI was evaluated.
Preoperative BNP levels did not predict postoperative AKI in this cohort of children undergoing cardiac operations. Both preoperative and postoperative BNP levels are associated with postoperative outcomes. Clinical Trial Registration at Clinicaltrials.gov as NCT00774137.
The Annals of thoracic surgery 04/2014; 97(6). DOI:10.1016/j.athoracsur.2014.02.035 · 3.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Urinary biomarkers of AKI provide prognostic value for in-hospital outcomes, but little is known about their association with longer-term mortality after surgery. We sought to assess the association between kidney injury biomarkers and all-cause mortality in an international, multicenter, prospective long-term follow-up study from six clinical centers in the United States and Canada composed of 1199 adults who underwent cardiac surgery between 2007 and 2009 and were enrolled in the Translational Research in Biomarker Endpoints in AKI cohort. On postoperative days 1-3, we measured the following five urinary biomarkers: neutrophil gelatinase-associated lipocalin, IL-18, kidney injury molecule-1 (KIM-1), liver fatty acid binding protein, and albumin. During a median follow-up of 3.0 years (interquartile range, 2.2-3.6 years), 139 participants died (55 deaths per 1000 person-years). Among patients with clinical AKI, the highest tertiles of peak urinary neutrophil gelatinase-associated lipocalin, IL-18, KIM-1, liver fatty acid binding protein, and albumin associated independently with a 2.0- to 3.2-fold increased risk for mortality compared with the lowest tertiles. In patients without clinical AKI, the highest tertiles of peak IL-18 and KIM-1 also associated independently with long-term mortality (adjusted hazard ratios [95% confidence intervals] of 1.2 [1.0 to 1.5] and 1.8 [1.4 to 2.3] for IL-18 and KIM-1, respectively), and yielded continuous net reclassification improvements of 0.26 and 0.37, respectively, for the prediction of 3-year mortality. In conclusion, urinary biomarkers of kidney injury, particularly IL-18 and KIM-1, in the immediate postoperative period provide additional prognostic information for 3-year mortality risk in patients with and without clinical AKI.
Journal of the American Society of Nephrology 12/2013; 25(5). DOI:10.1681/ASN.2013070742 · 9.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Using either an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) the morning of surgery may lead to 'functional' postoperative acute kidney injury (AKI), measured by an abrupt increase in serum creatinine. Whether the same is true for 'structural' AKI, measured with new urinary biomarkers, is unknown.
The TRIBE-AKI study was a prospective cohort study of 1594 adults undergoing cardiac surgery at six hospitals between July 2007 and December 2010. We classified the degree of exposure to ACEi/ARB into three categories: 'none' (no exposure prior to surgery), 'held' (on chronic ACEi/ARB but held on the morning of surgery) or 'continued' (on chronic ACEi/ARB and taken the morning of surgery). The co-primary outcomes were 'functional' AKI based upon changes in pre- to postoperative serum creatinine, and 'structural AKI', based upon peak postoperative levels of four urinary biomarkers of kidney injury.
Across the three levels (none, held and continued) of ACEi/ARB exposure there was a graded increase in functional AKI, as defined by AKI stage 1 or worse; (31, 34 and 42%, P for trend 0.03) and by percentage change in serum creatinine from pre- to postoperative (25, 26 and 30%, P for trend 0.03). In contrast, there were no differences in structural AKI across the strata of ACEi/ARB exposure, as assessed by four structural AKI biomarkers (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, interleukin-18 or liver-fatty acid-binding protein).
Preoperative ACEi/ARB usage was associated with functional but not structural acute kidney injury. As AKI from ACEi/ARB in this setting is unclear, interventional studies testing different strategies of perioperative ACEi/ARB use are warranted.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND AND OBJECTIVES: AKI is common and novel biomarkers may help provide earlier diagnosis and prognosis of AKI in the postoperative period. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a prospective, multicenter cohort study involving 1219 adults and 311 children consecutively enrolled at eight academic medical centers. Performance of two urine biomarkers, kidney injury molecule-1 (KIM-1) and liver fatty acid-binding protein (L-FABP), alone or in combination with other injury biomarkers during the perioperative period was evaluated. AKI was defined as doubling of serum creatinine or need for acute dialysis. RESULTS: KIM-1 peaked 2 days after surgery in adults and 1 day after surgery in children, whereas L-FABP peaked within 6 hours after surgery in both age groups. In multivariable analyses, the highest quintile of the first postoperative KIM-1 level was associated with AKI compared with the lowest quintile in adults, whereas the first postoperative L-FABP was not associated with AKI. Both KIM-1 and L-FABP were not significantly associated with AKI in adults or children after adjusting for other kidney injury biomarkers (neutrophil gelatinase-associated lipocalin and IL-18). The highest area under the curves achievable for discrimination for AKI were 0.78 in adults using urine KIM-1 from 6 to 12 hours, urine IL-18 from day 2, and plasma neutrophil gelatinase-associated lipocalin from day 2 and 0.78 in children using urine IL-18 from 0 to 6 hours and urine L-FABP from day 2. CONCLUSIONS: Postoperative elevations of KIM-1 associate with AKI and adverse outcmes in adults but were not independent of other AKI biomarkers. A panel of multiple biomarkers provided moderate discrimination for AKI.
Clinical Journal of the American Society of Nephrology 04/2013; 8(7). DOI:10.2215/CJN.10971012 · 5.25 Impact Factor
[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; 61(5). DOI:10.1053/j.ajkd.2012.12.006 · 5.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Evidence supports early use of non-biologic DMARDs to prevent irreversible damage in inflammatory arthritides, including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and possibly ankylosing spondylitis (AS). However, there is a paucity of data exploring their effects on pain as a primary outcome in these conditions. This systematic literature review investigated the effect of non-biologic DMARDs on pain levels in IA and examined whether disease duration impacted efficacy. We searched Medline, Embase, Cochrane Central, and Cochrane Database of Systematic Reviews, abstracts from the 2008 to 2010 American College of Rheumatology annual congresses, and citation lists of retrieved publications. Only randomized, double-blind controlled trials were analyzed. Quality was assessed with the Risk of Bias tool. Descriptive statistics were used in meta-analysis. 9,860 articles were identified, with 33 eligible for inclusion: 8 in AS, 6 in PsA, 9 in early RA (ERA), and 10 in established RA. In ERA and established RA, all studies of DMARDs (monotherapy and combination therapies) consistently revealed statistically significant reductions in pain except three oral gold studies. In AS, sulfasalazine studies showed significant pain reduction, whereas use of other DMARDs did not. In PsA, 5 of 6 studies reported VAS-pain improvement. From the studies included, we were unable to assess the influence of disease duration on pain outcomes in these rheumatic conditions. DMARDs improve pain in early and established RA. Sulfasalazine may improve pain in AS and PsA. Further study is needed to assess the relationship between disease duration and DMARD efficacy in reducing pain in these conditions.
Rheumatology International 01/2013; 33(5). DOI:10.1007/s00296-012-2619-6 · 1.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND:Escherichia coli O157:H7 is a common cause of acute bacterial gastroenteritis, which can be devastating in outbreak situations. We studied the risk of cardiovascular disease following such an outbreak in Walkerton, Ontario, in May 2000. METHODS:In this community-based cohort study, we linked data from the Walkerton Health Study (2002-2008) to Ontario's large healthcare databases. We included 4 groups of adults: 3 groups of Walkerton participants (153 with severe gastroenteritis, 414 with mild gastroenteritis, 331 with no gastroenteritis) and a group of 11 263 residents from the surrounding communities that were unaffected by the outbreak. The primary outcome was a composite of death or first major cardiovascular event (admission to hospital for acute myocardial infarction, stroke or congestive heart failure, or evidence of associated procedures). The secondary outcome was first major cardiovascular event censored for death. Adults were followed for an average of 7.4 years. RESULTS:During the study period, 1174 adults (9.7%) died or experienced a major cardiovascular event. Compared with residents of the surrounding communities, the risk of death or cardiovascular event was not elevated among Walkerton participants with severe or mild gastroenteritis (hazard ratio [HR] for severe gastroenteritis 0.74, 95% confidence interval [CI] 0.38-1.43, mild gastroenteritis HR 0.64, 95% CI 0.42-0.98). Compared with Walkerton participants who had no gastroenteritis, risk of death or cardiovascular event was not elevated among participants with severe or mild gastroenteritis. INTERPRETATION:There was no increase in the risk of cardiovascular disease in the decade following acute infection during a major E. coli O157:H7 outbreak.
Canadian Medical Association Journal 11/2012; 185(1). DOI:10.1503/cmaj.112161 · 5.81 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; 60(6). DOI:10.1053/j.ajkd.2012.06.002 · 5.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Current tools to predict outcomes after kidney transplantation are inadequate. The objective of this study was to determine the association of perioperative urine neutrophil gelatinase-associated lipocalin and IL-18 with poor 1-year allograft function (return to dialysis or estimated GFR<30 ml/min per 1.73 m(2)).
Neutrophil gelatinase-associated lipocalin and IL-18 from early post-transplant urine was measured in this prospective, multicenter study of deceased-donor kidney transplant recipients. The outcome of poor allograft function at 1 year relative to these biomarkers using multivariable logistic regression and net reclassification improvement was examined. Also, the interaction between delayed graft function and the biomarkers on the outcome were evaluated, and the change in biomarkers over consecutive days related to the outcome using trend tests was examined.
Mean age for the 153 recipients was 54 ± 13 years. Delayed graft function occurred in 42%, and 24 (16%) recipients had the 1-year outcome. Upper median values for neutrophil gelatinase-associated lipocalin and IL-18 on the first postoperative day had adjusted odds ratios (95% confidence interval) of 6.0 (1.5-24.0) and 5.5 (1.4-21.5), respectively. Net reclassification improvement (95% confidence interval) was significant for neutrophil gelatinase-associated lipocalin and IL-18 at 36% (1%-71%) and 45% (8%-83%), respectively. There was no significant interaction between biomarkers and delayed graft function on the outcome. Change in biomarkers moderately trended with the outcome.
Perioperative urine neutrophil gelatinase-associated lipocalin and IL-18 are associated with poor 1-year allograft function, suggesting their potential for identifying patients for therapies that minimize the risk of additional injury.
Clinical Journal of the American Society of Nephrology 06/2012; 7(8):1224-33. DOI:10.2215/CJN.00310112 · 5.25 Impact Factor