Dataset Information

Analysis of a urinary biomarker panel for incident kidney disease and clinical outcomes.

ABSTRACT: Whether novel biomarkers improve the assessment of incident kidney disease and related adverse outcomes remains to be tested in longitudinal observational studies. We tested 14 urinary biomarkers for association with incident kidney, cardiovascular, and mortality outcomes in 2948 Framingham Heart Study participants. Baseline examinations were performed between 1995 and 1998; mean follow-up was 10.1 years for renal outcomes and 11.2 years for survival analyses. Primary outcomes were incident CKD, incident albuminuria, incident cardiovascular disease, and all-cause mortality. Secondary analyses assessed incident congestive heart failure (CHF) and mortality with coexistent kidney disease. Biomarkers were tested for association with renal end points using logistic regression and incident cardiovascular and mortality outcomes in proportional hazards models; ?1-microglobulin, Kim-1, and TFF-3 predicted all-cause mortality (hazard ratio per SD increase in log-transformed biomarker [HR] range, 1.15 to 1.21; 95% confidence interval [CI] range, 1.04 to 1.34; P values=0.007 to <0.001), whereas ?1-microglobulin, ?2-microglobulin, KIM-1, and TFF-3 associated with death with coexistent kidney disease (HR range, 1.72-2.25; 95% CI, 1.17 to 3.24; P values<0.01). KIM-1 also associated with the risk of incident CHF (HR, 1.32; 95% CI, 1.07 to 1.63; P=0.008). CTGF associated nominally with CKD (HR, 0.83; 95% CI, 0.71 to 0.98; P=0.03), but no other biomarkers associated with incident CKD or albuminuria. Addition of ?1-microglobulin and TFF-3 resulted in a nonsignificant net reclassification index (NRI) of 3% for all-cause mortality beyond clinical risk factors. In conclusion, components of a panel of 14 subclinical biomarkers of kidney injury were associated with important clinical outcomes and merit additional investigation.

SUBMITTER: O'Seaghdha CM

PROVIDER: S-EPMC3810081 | biostudies-other | 2013 Nov

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Analysis of a urinary biomarker panel for incident kidney disease and clinical outcomes.

O'Seaghdha Conall M CM Hwang Shih-Jen SJ Larson Martin G MG Meigs James B JB Vasan Ramachandran S RS Fox Caroline S CS

Journal of the American Society of Nephrology : JASN 20130829 11

Whether novel biomarkers improve the assessment of incident kidney disease and related adverse outcomes remains to be tested in longitudinal observational studies. We tested 14 urinary biomarkers for association with incident kidney, cardiovascular, and mortality outcomes in 2948 Framingham Heart Study participants. Baseline examinations were performed between 1995 and 1998; mean follow-up was 10.1 years for renal outcomes and 11.2 years for survival analyses. Primary outcomes were incident CKD, ...[more]

PMID: 23990678

Similar Datasets

Project description:ObjectivesThe aim of this study was to examine the efficacy and safety of warfarin initiation following the diagnosis of atrial fibrillation (AF) in patients with late-stage chronic kidney disease (CKD) who transitioned to dialysis.BackgroundThe clinical benefit of warfarin therapy for thromboprophylaxis after incident AF diagnosis in patients with late-stage CKD who are transitioning to dialysis is unknown.MethodsIn this retrospective cohort analysis, the study population was a national cohort of 22,771 U.S. veterans with incident end-stage renal disease who developed incident AF before initiating renal replacement therapy. This study examined the association of warfarin therapy following the diagnosis of incident AF with ischemic cerebrovascular accidents (CVAs) (ischemic stroke or transient ischemic attack), ischemic CVA-related hospitalization, major bleeding events (gastrointestinal or intracranial bleeding), bleeding event-related hospitalizations, and post-dialysis, all-cause mortality in multivariable adjusted Cox regression analyses that adjusted for demographic characteristics and comorbidities.ResultsThe mean ± SD age of the cohort was 73.5 ± 8.8 years, 13% were African American, and the mean CHA2DS2-VASc score was 5.7 ± 2.1. Of the overall cohort, 6,682 (29.3%) patients were started on warfarin during the follow-up period. The hazard ratios (95% confidence intervals) for ischemic CVA, bleeding events, and death for those started on warfarin were 1.23 (1.16 to 1.30), 1.36 (1.29 to 1.44), and 0.94 (0.90 to 0.97), respectively, compared with those who received no anticoagulation. Warfarin exposure was associated with higher risk for ischemic CVA and bleeding event-related hospitalizations.ConclusionsIn patients with late-stage CKD who transitioned to dialysis, warfarin use was associated with higher risk of ischemic and bleeding events but a lower risk of mortality. Future studies such as those comparing warfarin with newer oral anticoagulant agents are needed to granularly define the net clinical benefit of anticoagulation therapy in patients with advanced CKD with incident AF.

Project description:Acute and chronic kidney disease continues to confer significant morbidity and mortality in the clinical setting. Despite high prevalence of these conditions, few validated biomarkers exist to predict kidney dysfunction. In this study, we utilized a novel kidney multiplex panel to measure 21 proteins in plasma and urine to characterize the spectrum of biomarker profiles in kidney disease. Blood and urine samples were obtained from age-/sex-matched healthy control subjects (HC), critically-ill COVID-19 patients with acute kidney injury (AKI), and patients with chronic or end-stage kidney disease (CKD/ESKD). Biomarkers were measured with a kidney multiplex panel, and results analyzed with conventional statistics and machine learning. Correlations were examined between biomarkers and patient clinical and laboratory variables. Median AKI subject age was 65.5 (IQR 58.5-73.0) and median CKD/ESKD age was 65.0 (IQR 50.0-71.5). Of the CKD/ESKD patients, 76.1% were on hemodialysis, 14.3% of patients had kidney transplant, and 9.5% had CKD without kidney replacement therapy. In plasma, 19 proteins were significantly different in titer between the HC versus AKI versus CKD/ESKD groups, while NAG and RBP4 were unchanged. TIMP-1 (PPV 1.0, NPV 1.0), best distinguished AKI from HC, and TFF3 (PPV 0.99, NPV 0.89) best distinguished CKD/ESKD from HC. In urine, 18 proteins were significantly different between groups except Calbindin, Osteopontin and TIMP-1. Osteoactivin (PPV 0.95, NPV 0.95) best distinguished AKI from HC, and β2-microglobulin (PPV 0.96, NPV 0.78) best distinguished CKD/ESKD from HC. A variety of correlations were noted between patient variables and either plasma or urine biomarkers. Using a novel kidney multiplex biomarker panel, together with conventional statistics and machine learning, we identified unique biomarker profiles in the plasma and urine of patients with AKI and CKD/ESKD. We demonstrated correlations between biomarker profiles and patient clinical variables. Our exploratory study provides biomarker data for future hypothesis driven research on kidney disease.

Dataset Information

Analysis of a urinary biomarker panel for incident kidney disease and clinical outcomes.

Publications

Analysis of a urinary biomarker panel for incident kidney disease and clinical outcomes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets