Dataset Information

FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis.

ABSTRACT: Concentrations of the phosphate-regulating hormone fibroblast growth factor-23 (FGF-23) are elevated in patients with chronic kidney disease (CKD), but whether higher plasma FGF-23 concentrations associate with all-cause mortality, cardiovascular events, or initiation of chronic dialysis is not completely understood. Here, we measured FGF-23 concentration in stored plasma samples from 1099 patients with advanced CKD who participated in The Homocysteine in Kidney and End Stage Renal Disease study. Mean serum phosphorus concentration was 4.3 mg/dl, median FGF-23 concentration was 392 RU/ml, and mean GFR was 18 ml/min/1.73 m(2). During a median follow-up of 2.9 yr, 453 (41%) patients died from any cause, 215 (20%) had a cardiovascular event, and 615 (56%) initiated chronic dialysis. Compared with the lowest quartile of FGF-23, each subsequent quartile associated with a progressively higher risk for death, adjusted for confounders (HR [95% CI] of 1.24 [0.91 to 1.69], 1.76 [1.28 to 2.44], and 2.17 [1.56 to 3.08] for the second through fourth quartiles, respectively). In addition, compared with the lowest quartile, the two highest quartiles of FGF-23 also associated with a significantly elevated risk for cardiovascular events and initiation of chronic dialysis. In conclusion, in advanced CKD, FGF-23 strongly and independently associates with all-cause mortality, cardiovascular events, and initiation of chronic dialysis.

SUBMITTER: Kendrick J

PROVIDER: S-EPMC3187186 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis.

Kendrick Jessica J Cheung Alfred K AK Kaufman James S JS Greene Tom T Roberts William L WL Smits Gerard G Chonchol Michel M

Journal of the American Society of Nephrology : JASN 20110907 10

Concentrations of the phosphate-regulating hormone fibroblast growth factor-23 (FGF-23) are elevated in patients with chronic kidney disease (CKD), but whether higher plasma FGF-23 concentrations associate with all-cause mortality, cardiovascular events, or initiation of chronic dialysis is not completely understood. Here, we measured FGF-23 concentration in stored plasma samples from 1099 patients with advanced CKD who participated in The Homocysteine in Kidney and End Stage Renal Disease study ...[more]

PMID: 21903574

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Project description:ObjectiveTo identify the optimal estimated glomerular filtration rate (eGFR) at which to initiate dialysis in people with advanced chronic kidney disease.DesignNationwide observational cohort study.SettingNational Swedish Renal Registry of patients referred to nephrologists.ParticipantsPatients had a baseline eGFR between 10 and 20 mL/min/1.73 m2 and were included between 1 January 2007 and 31 December 2016, with follow-up until 1 June 2017.Main outcome measuresThe strict design criteria of a clinical trial were mimicked by using the cloning, censoring, and weighting method to eliminate immortal time bias, lead time bias, and survivor bias. A dynamic marginal structural model was used to estimate adjusted hazard ratios and absolute risks for five year all cause mortality and major adverse cardiovascular events (composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) for 15 dialysis initiation strategies with eGFR values between 4 and 19 mL/min/1.73 m2 in increments of 1 mL/min/1.73 m2. An eGFR between 6 and 7 mL/min/1.73 m2 (eGFR6-7) was taken as the reference.ResultsAmong 10 290 incident patients with advanced chronic kidney disease (median age 73 years; 3739 (36%) women; median eGFR 16.8 mL/min/1.73 m2), 3822 started dialysis, 4160 died, and 2446 had a major adverse cardiovascular event. A parabolic relation was observed for mortality, with the lowest risk for eGFR15-16. Compared with dialysis initiation at eGFR6-7, initiation at eGFR15-16 was associated with a 5.1% (95% confidence interval 2.5% to 6.9%) lower absolute five year mortality risk and 2.9% (0.2% to 5.5%) lower risk of a major adverse cardiovascular event, corresponding to hazard ratios of 0.89 (95% confidence interval 0.87 to 0.92) and 0.94 (0.91 to 0.98), respectively. This 5.1% absolute risk difference corresponded to a mean postponement of death of 1.6 months over five years of follow-up. However, dialysis would need to be started four years earlier. When emulating the intended strategies of the Initiating Dialysis Early and Late (IDEAL) trial (eGFR10-14 v eGFR5-7) and the achieved eGFRs in IDEAL (eGFR7-10 v eGFR5-7), hazard ratios for all cause mortality were 0.96 (0.94 to 0.99) and 0.97 (0.94 to 1.00), respectively, which are congruent with the findings of the randomised IDEAL trial.ConclusionsVery early initiation of dialysis was associated with a modest reduction in mortality and cardiovascular events. For most patients, such a reduction may not outweigh the burden of a substantially longer period spent on dialysis.

Project description:BackgroundThe Canadian Study of Prediction of Death, Dialysis and Interim Cardiovascular Events (CanPREDDICT) is a large, prospective, pan-Canadian, cohort study designed to improve our understanding of determinants of renal and cardiovascular (CV) disease progression in patients with chronic kidney disease (CKD). The primary objective is to clarify the associations between traditional and newer biomarkers in the prediction of specific renal and CV events, and of death in patients with CKD managed by nephrologists. This information could then be used to better understand biological variation in outcomes, to develop clinical prediction models and to inform enrolment into interventional studies which may lead to novel treatments.Methods/designsCommenced in 2008, 2546 patients have been enrolled with eGFR between 15 and 45 ml/min 1.73m2 from a representative sample in 25 rural, urban, academic and non academic centres across Canada. Patients are to be followed for an initial 3 years at 6 monthly intervals, and subsequently annually. Traditional biomarkers include eGFR, urine albumin creatinine ratio (uACR), hemoglobin (Hgb), phosphate and albumin. Newer biomarkers of interest were selected on the basis of biological relevance to important processes, commercial availability and assay reproducibility. They include asymmetric dimethylarginine (ADMA), N-terminal pro-brain natriuretic peptide (NT-pro-BNP), troponin I, cystatin C, high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6) and transforming growth factor beta 1 (TGFβ1). Blood and urine samples are collected at baseline, and every 6 monthly, and stored at -80°C. Outcomes of interest include renal replacement therapy, CV events and death, the latter two of which are adjudicated by an independent panel.DiscussionThe baseline distribution of newer biomarkers does not appear to track to markers of kidney function and therefore may offer some discriminatory value in predicting future outcomes. The granularity of the data presented at baseline may foster additional questions.The value of the cohort as a unique resource to understand outcomes of patients under the care of nephrologists in a single payer healthcare system cannot be overstated. Systematic collection of demographic, laboratory and event data should lead to new insights. The mean age of the cohort was 68 years, 90% were Caucasian, 62% were male, and 48% had diabetes. Forty percent of the cohort had eGFR between 30-45 mL/min/1.73m², 22% had eGFR values below 20 mL/min/1.73m²; 61% had uACR < 30. Serum albumin, hemoglobin, calcium and 25-hydroxyvitamin D (25(OH)D) levels were progressively lower in the lower eGFR strata, while parathyroid hormone (PTH) levels increased. Cystatin C, ADMA, NT-proBNP, hsCRP, troponin I and IL-6 were significantly higher in the lower GFR strata, whereas 25(OH)D and TGFβ1 values were lower at lower GFR. These distributions of each of the newer biomarkers by eGFR and uACR categories were variable.

Project description:OBJECTIVES:This study sought to determine the association of fibroblast growth factor (FGF)-23 with death, heart failure (HF), and cardiovascular disease (CVD) in the general population, as well as the influence of chronic kidney disease (CKD) in this setting. BACKGROUND:FGF-23 increases renal phosphorus excretion and inhibits vitamin D activation. In end-stage renal disease, high FGF-23 levels are associated with mortality. The association of FGF-23 with death, HF, and CVD in the general population, and the influence of CKD in this setting, are unknown. METHODS:Plasma FGF-23 was measured in 3,107 community-living persons ? 65 years of age in 1996 and 1997, and participants were followed through 2008. HF and CVD events were adjudicated by a panel of experts. Associations of FGF-23 with each outcome were evaluated using Cox proportional hazards models, and we tested whether associations differed by CKD status. RESULTS:Both lower estimated glomerular filtration rate and higher urine albumin to creatinine ratios were associated with high FGF-23 at baseline. During 10.5 years (median) follow-up, there were 1,730 deaths, 697 incident HF events, and 797 incident CVD events. Although high FGF-23 concentrations were associated with each outcome in combined analyses, the associations were consistently stronger for those with CKD (p interactions all <0.006). In the CKD group (n = 1,128), the highest FGF-23 quartile had adjusted hazards ratios (HR) of 1.87 (95% confidence interval [CI]: 1.47 to 2.38) for all-cause death, 1.94 (95% CI: 1.32 to 2.83) for incident HF, and 1.49 (95% CI: 1.02 to 2.18) for incident CVD events compared with the lowest quartile. Corresponding HRs in those without CKD (n = 1,979) were 1.29 (95% CI: 1.05 to 1.59), 1.37 (95% CI: 0.99 to 1.89), and 1.07 (95% CI: 0.79 to 1.45). CONCLUSIONS:FGF-23, a hormone involved in phosphorous and vitamin D homeostasis, is independently associated with all-cause death and incident HF in community-living older persons. These associations appear stronger in persons with CKD.

Project description:Background and objectivesCardiovascular (CV) disease is the main cause of morbidity and mortality in patients suffering from chronic kidney disease (CKD). Although it is widely recognized that CV risk assessment represents an essential prerequisite for clinical management, existing prognostic models appear not to be entirely adequate for CKD patients. We derived a literature-based, naïve-bayes model predicting the yearly risk of CV hospitalizations among patients suffering from CKD, referred as the CArdiovascular, LIterature-Based, Risk Algorithm (CALIBRA).MethodsCALIBRA incorporates 31 variables including traditional and CKD-specific risk factors. It was validated in two independent CKD populations: the FMC NephroCare cohort (European Clinical Database, EuCliD®) and the German Chronic Kidney Disease (GCKD) study prospective cohort. CALIBRA performance was evaluated by c-statistics and calibration charts. In addition, CALIBRA discrimination was compared with that of three validated tools currently used for CV prediction in CKD, namely the Framingham Heart Study (FHS) risk score, the atherosclerotic cardiovascular disease risk score (ASCVD), and the Individual Data Analysis of Antihypertensive Intervention Trials (INDANA) calculator. Superiority was defined as a ΔAUC>0.05.ResultsCALIBRA showed good discrimination in both the EuCliD® medical registry (AUC 0.79, 95%CI 0.76-0.81) and the GCKD cohort (AUC 0.73, 95%CI 0.70-0.76). CALIBRA demonstrated improved accuracy compared to the benchmark models in EuCliD® (FHS: ΔAUC=-0.22, p<0.001; ASCVD: ΔAUC=-0.17, p<0.001; INDANA: ΔAUC=-0.14, p<0.001) and GCKD (FHS: ΔAUC=-0.16, p<0.001; ASCVD: ΔAUC=-0.12, p<0.001; INDANA: ΔAUC=-0.04, p<0.001) populations. Accuracy of the CALIBRA score was stable also for patients showing missing variables.ConclusionCALIBRA provides accurate and robust stratification of CKD patients according to CV risk and allows score calculations with improved accuracy compared to established CV risk scores also in real-world clinical cohorts with considerable missingness rates. Our results support the generalizability of CALIBRA across different CKD populations and clinical settings.

Project description:Glucagon-like Peptide-1 Receptor Agonists (GLP-1RAs) have demonstrated efficacy in improving mortality and cardiovascular (CV) outcomes. However, the impact of GLP-1RAs therapy on cardiorenal outcomes of diabetic patients at the commencement of dialysis remains unexplored. This study aimed to investigate the long-term benefits of GLP-1RAs in type 2 diabetic patients at dialysis commencement. A cohort of type 2 diabetic patients initializing dialysis was identified from the TriNetX global database. Patients treated with GLP-1RAs and those treated with long-acting insulin (LAI) were matched by propensity score. We focused on all-cause mortality, four-point major adverse cardiovascular events (4p-MACE), and major adverse kidney events (MAKE). Among 82,041 type 2 diabetic patients initializing dialysis, 2.1% (n = 1685) patients were GLP-1RAs users (mean ages 59.3 years; 55.4% male). 1682 patients were included in the propensity-matched group, treated either with GLP-1RAs or LAI. The main causes of acute dialysis in this study were ischemic heart disease (17.2%), followed by heart failure (13.6%) and sepsis (6.5%). Following a median follow-up of 1.4 years, GLP-1RAs uses at dialysis commencement was associated with a reduced risk of mortality (hazard ratio [HR] = 0.63, p < 0.001), 4p-MACE (HR = 0.65, p < 0.001), and MAKE (HR = 0.75, p < 0.001). This association was particularly notable in long-acting GLP-1RAs users, with higher BMI, lower HbA1c, and those with eGFR > 15 ml/min/1.73m2. GLP-1RAs' new use at dialysis commencement was significantly associated with a lower risk of MACE (p = 0.047) and MAKE (p = 0.004). Additionally, GLP-1RAs use among those who could discontinue from acute dialysis or long-term RAs users was associated with a lower risk of mortality, 4p-MACE, and MAKE. Given to the limitations of this observational study, use of GLP-1RAs at the onset of dialysis was associated with a decreased risk of MACE, MAKE, and all-cause mortality. These findings show the lack of harm associated with the use of GLP-1RAs in diabetic patients at the initiation of acute dialysis.

Dataset Information

FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis.

Publications

FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis.

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