Dataset Information

Urinary biomarkers and progression of AKI in patients with cirrhosis.

ABSTRACT:

Background and objectives

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.

Design, setting, participants, & measurements

A multicenter, prospective cohort study was conducted at four tertiary care United States medical centers between 2009 and 2011. The study comprised patients with cirrhosis and AKI defined by the AKI Network criteria evaluating structural (neutrophil gelatinase-associated lipocalin, IL-18, kidney injury molecule-1 [KIM-1], liver-type fatty acid-binding protein [L-FABP], and albuminuria) and functional (fractional excretion of sodium [FENa]) urinary biomarkers as predictors of AKI progression and in-hospital mortality.

Results

Of 188 patients in the study, 44 (23%) experienced AKI progression alone and 39 (21%) suffered both progression and death during their hospitalization. Neutrophil gelatinase-associated lipocalin, IL-18, KIM-1, L-FABP, and albuminuria were significantly higher in patients with AKI progression and death. These biomarkers were independently associated with this outcome after adjusting for key clinical variables including model of end stage liver disease score, IL-18 (relative risk [RR], 4.09; 95% confidence interval [95% CI], 1.56 to 10.70), KIM-1 (RR, 3.13; 95% CI, 1.20 to 8.17), L-FABP (RR, 3.43; 95% CI, 1.54 to 7.64), and albuminuria (RR, 2.07; 95% CI, 1.05-4.10) per log change. No biomarkers were independently associated with progression without mortality. FENa demonstrated no association with worsening of AKI. When added to a robust clinical model, only IL-18 independently improved risk stratification on a net reclassification index.

Conclusions

Multiple structural biomarkers of kidney injury, but not FENa, are independently associated with progression of AKI and mortality in patients with cirrhosis. Injury marker levels were similar between those without progression and those with progression alone.

SUBMITTER: Belcher JM

PROVIDER: S-EPMC4220770 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Urinary biomarkers and progression of AKI in patients with cirrhosis.

Belcher Justin M JM Garcia-Tsao Guadalupe G Sanyal Arun J AJ Thiessen-Philbrook Heather H Peixoto Aldo J AJ Perazella Mark A MA Ansari Naheed N Lim Joseph J Coca Steven G SG Parikh Chirag R CR

Clinical journal of the American Society of Nephrology : CJASN 20140902 11

<h4>Background and objectives</h4>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 i ...[more]

PMID: 25183658

Similar Datasets

Project description:Background and objectivesA major challenge in early treatment of acute cardiorenal syndrome (CRS) is the lack of predictors for progression of AKI. We aim to investigate the utility of urinary angiotensinogen and other renal injury biomarkers in predicting AKI progression in CRS.Design, settings, participants, & measurementsIn this prospective, multicenter study, we screened 732 adults who admitted for acute decompensated heart failure from September 2011 to December 2014, and evaluated whether renal injury biomarkers measured at time of AKI diagnosis can predict worsening of AKI. In 213 patients who developed Kidney Disease Improving Global Outcomes stage 1 or 2 AKI, six renal injury biomarkers, including urinary angiotensinogen (uAGT), urinary neutrophil gelatinase-associated lipocalin (uNGAL), plasma neutrophil gelatinase-associated lipocalin, urinary IL-18 (uIL-18), urinary kidney injury molecule-1, and urinary albumin-to-creatinine ratio, were measured at time of AKI diagnosis. The primary outcome was AKI progression defined by worsening of AKI stage (50 patients). The secondary outcome was AKI progression with subsequent death (18 patients).ResultsAfter multivariable adjustment, the highest tertile of three urinary biomarkers remained associated with AKI progression compared with the lowest tertile: uAGT (odds ratio [OR], 10.8; 95% confidence interval [95% CI], 3.4 to 34.7), uNGAL (OR, 4.7; 95% CI, 1.7 to 13.4), and uIL-18 (OR, 3.6; 95% CI, 1.4 to 9.5). uAGT was the best predictor for both primary and secondary outcomes with area under the receiver operating curve of 0.78 and 0.85. These three biomarkers improved risk reclassification compared with the clinical model alone, with uAGT performing the best (category-free net reclassification improvement for primary and secondary outcomes of 0.76 [95% CI, 0.46 to 1.06] and 0.93 [95% CI, 0.50 to 1.36]; P<0.001). Excellent performance of uAGT was further confirmed with bootstrap internal validation.ConclusionsuAGT, uNGAL, and uIL-18 measured at time of AKI diagnosis improved risk stratification and identified CRS patients at highest risk of adverse outcomes.

Project description:BACKGROUND AND OBJECTIVES:Literature on the prognosis of patients with cirrhosis who require RRT for AKI is sparse and is confounded by liver transplant eligibility. An update on outcomes in the nonlisted subgroup is needed. Our objective was to compare outcomes in this group between those diagnosed with hepatorenal syndrome and acute tubular necrosis, stratifying by liver transplant listing status. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Retrospective cohort study of patients with cirrhosis acutely initiated on hemodialysis or continuous RRT at five hospitals, including one liver transplant center. Multivariable regression and survival analysis were performed. RESULTS:Four hundred seventy-two subjects were analyzed (341 not listed and 131 listed for liver transplant). Among nonlisted subjects, 15% (51 of 341) were alive at 6 months after initiating RRT. Median survival was 21 (interquartile range [IQR], 8, 70) days for those diagnosed with hepatorenal syndrome and 12 (IQR, 3, 43) days for those diagnosed with acute tubular necrosis (P=0.25). Among listed subjects, 48% (63 of 131) received a liver transplant. Median transplant-free survival was 15 (IQR, 5, 37) days for those diagnosed with hepatorenal syndrome and 14 (IQR, 4, 31) days for those diagnosed with acute tubular necrosis (P=0.60). When stratified by transplant listing, with adjusted Cox models we did not detect a difference in the risk of death between hepatorenal syndrome and acute tubular necrosis (hazard ratio [HR], 0.81; 95% confidence interval [95% CI], 0.59 to 1.11, among those not listed; HR, 0.73; 95% CI, 0.44 to 1.19, among those listed). CONCLUSIONS:Cause of AKI was not significantly associated with mortality in patients with cirrhosis who required RRT. Among those not listed for liver transplant, mortality rates were extremely high in patients both with hepatorenal syndrome and acute tubular necrosis. PODCAST:This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_11_09_CJASNPodcast_18_1_A.mp3.

Project description:Backgrounds: Kidney biomarkers in urine appear to be useful in differential diagnosis between acute tubular necrosis and other types of acute kidney injury (AKI) in cirrhosis. In clinical practice, prerenal azotemia (PRA) is often distinguished from other types of AKI by volume expansion therapy. The aim of the current study was to investigate the accuracy of urinary biomarkers in the differential diagnosis between PRA and other types of AKI. Methods: A total of 65 patients with hepatitis B cirrhosis were prospectively included and divided into AKI and non-AKI groups. Patients with hepatitis B cirrhosis and AKI discontinue diuretics, vasodilators, and nephrotoxic drugs and give volume expansion therapy. The efficacy was judged after 48 h of treatment. Urinary biomarkers were measured at the time of diagnosis of AKI and 48 h after volume expansion therapy. Univariate and multivariate analyses were used to identify independent risk factors for nonresponse to volume expansion therapy. Results: Of the 65 patients, 49 patients with newly diagnosed AKI were screened in the study, and 16 hospitalized patients with hepatitis B cirrhosis without AKI at the same period were screened as the control group. In patients with cirrhosis and AKI, 29 (59.18%) patients were in the response group and 20 (40.81%) patients were in the nonresponse group. The mortality rate in the nonresponse group was significantly higher than that in the response group (75% vs. 13.8% p < 0.001). After logistic regression analysis, urinary neutrophil gelatinase-associated lipocalin (NGAL) and serum creatinine (SCr) at diagnosis of AKI showed significant association with nonresponse to volume expansion therapy. The cutoff values for SCr and urinary NGAL were 128.50 µmol/L and 90.75 ng/ml, respectively. The area under the receiver operating curve (AUC) for SCr and urinary NGAL was 0.815 and 0.831. Conclusion: Elevated urinary NGAL can reflect the degree of kidney injury and is an independent risk factor for nonresponse to volume expansion therapy in patients with hepatitis B cirrhosis and AKI.

Project description:Introduction:The variable disease course of autosomal dominant polycystic kidney disease (ADPKD) makes it important to develop biomarkers that can predict disease progression, from a patient perspective and to select patients for renoprotective treatment. We therefore investigated whether easy-to-measure urinary biomarkers are associated with disease progression and have additional value over that of conventional risk markers. Methods:At baseline, inflammatory, glomerular, and tubular damage markers were measured in 24-hour urine collections (albumin, IgG, kidney injury molecule-1 (KIM-1), N-acetyl-?-d-glucosaminidase (NAG), ?2 microglobulin (?2MG), heart-type fatty acid binding protein (HFABP), macrophage migration inhibitory factor (MIF), neutrophil gelatinase-associated lipocalin (NGAL), and monocyte chemotactic protein-1 (MCP-1). Disease progression was expressed as annual change in estimated glomerular filtration rate (eGFR, Chronic Kidney Disease EPIdemiology equation), measured glomerular filtation rate (mGFR, using 125I-iothalamate), or height-adjusted total kidney volume (htTKV). Multivariable linear regression was used to assess associations of these markers independent of conventional risk markers. Results:A total of 104 ADPKD patients were included (40 ± 11 years, 39% female, eGFR 77 ± 30, mGFR 79 ± 30 ml/min per 1.73 m2 and htTKV 852 [510-1244] ml/m). In particular, ?2MG and MCP-1 were associated with annual change in eGFR, and remained associated after adjustment for conventional risk markers (standardized ? = -0.35, P = 0.001, and standardized ? = -0.29, P = 0.009, respectively). Adding ?2MG and MCP-1 to a model containing conventional risk markers that explained annual change in eGFR significantly increased the performance of the model (final R2 = 0.152 vs. 0.292, P = 0.001). Essentially similar results were obtained when only patients with an eGFR ? 60 ml/min per 1.73 m2 were selected, or when change in mGFR was studied. Associations with change in htTKV were less strong. Conclusion:Urinary ?2MG and MCP-1 excretion were both associated with GFR decline in ADPKD, and had added value beyond that of conventional risk markers. These markers therefore have the potential to serve as predictive tools for clinical practice.

Project description:IntroductionCurrently, no effective therapies exist to reduce the high mortality associated with dialysis-dependent acute kidney injury (AKI-D). Serum biomarkers may be useful in understanding the pathophysiological processes involved with AKI and the severity of injury, and point to novel therapeutic targets.MethodsStudy day 1 serum samples from 100 patients and day 8 samples from 107 patients enrolled in the Veteran's Affairs/National Institutes of Health Acute Renal Failure Trial Network study were analyzed by the slow off-rate modified aptamers scan proteomic platform to profile 1305 proteins in each sample. Patients in each cohort were classified into tertiles based on baseline biomarker measurements. Cox regression analyses were performed to examine the relationships between serum levels of each biomarker and mortality.ResultsChanges in the serum levels of 54 proteins, 33 of which increased and 21 of which decreased, were detected when comparing samples of patients who died in the first 8 days versus patients who survived >8 days. Among the 33 proteins that increased, higher serum levels of fibroblast growth factor-23 (FGF23), tissue plasminogen activator (tPA), neutrophil collagenase (matrix metalloproteinase-8), and soluble urokinase plasminogen activator receptor, when stratified by tertiles, were associated with higher mortality. The association with mortality persisted for each of these proteins after adjusting for other potential risk factors, including age, sex, cardiovascular sequential organ failure assessment score, congestive heart failure, and presence of diabetes. Upper tertile levels of FGF23, tPA, and interleukin-6 on day 8 were associated with increased mortality; however, FGF23 barely lost significance after multivariable adjustment.ConclusionsOur results underscore an emerging proteomics tool capable of identifying low-abundance serum proteins important not only in the pathogenesis of AKI-D, but which is also helpful in discriminating AKI-D patients with high mortality.

Dataset Information

Urinary biomarkers and progression of AKI in patients with cirrhosis.

Background and objectives

Design, setting, participants, & measurements

Results

Conclusions

Publications

Urinary biomarkers and progression of AKI in patients with cirrhosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets