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Candidate gene analysis of arteriovenous fistula failure in hemodialysis patients.

ABSTRACT: BACKGROUND AND OBJECTIVES: Arteriovenous fistula (AVF) failure remains an important cause of morbidity in hemodialysis patients. The exact underlying mechanisms responsible for AVF failure are unknown but processes like proliferation, inflammation, vascular remodeling, and thrombosis are thought to be involved. The current objective was to investigate the association between AVF failure and single nucleotide polymorphisms (SNPs) in genes related to these pathophysiologic processes in a large population of incident hemodialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 479 incident hemodialysis patients were included between January 1997 and April 2004. Follow-up lasted 2 years or until AVF failure, defined as surgery, percutaneous endovascular intervention, or abandonment of the vascular access. Forty-three SNPs in 26 genes, related to proliferation, inflammation, endothelial function, vascular remodeling, coagulation, and calcium/phosphate metabolism, were genotyped. Relations were analyzed using Cox regression analysis. RESULTS: In total, 207 (43.2%) patients developed AVF failure. After adjustment, two SNPs were significantly associated with an increased risk of AVF failure. The hazard ratio (95% confidence interval) of LRP1 rs1466535 was 1.75 (1.15 to 2.66) and patients with factor V Leiden had a hazard ratio of 2.54 (1.41 to 4.56) to develop AVF failure. The other SNPs were not associated with AVF failure. CONCLUSIONS: In this large cohort of hemodialysis patients, only 2 of the 43 candidate SNPs were associated with an increased risk of AVF failure. Whether other factors, like local hemodynamic circumstances, are more important or other SNPs play a role in AVF failure remains to be elucidated.

SUBMITTER: Verschuren JJ

PROVIDER: S-EPMC3731912 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Candidate gene analysis of arteriovenous fistula failure in hemodialysis patients.

Verschuren Jeffrey J W JJ Ocak Gurbey G Dekker Friedo W FW Rabelink Ton J TJ Jukema J Wouter JW Rotmans Joris I JI

Clinical journal of the American Society of Nephrology : CJASN 20130404 8

<h4>Background and objectives</h4>Arteriovenous fistula (AVF) failure remains an important cause of morbidity in hemodialysis patients. The exact underlying mechanisms responsible for AVF failure are unknown but processes like proliferation, inflammation, vascular remodeling, and thrombosis are thought to be involved. The current objective was to investigate the association between AVF failure and single nucleotide polymorphisms (SNPs) in genes related to these pathophysiologic processes in a la ...[more]

PMID: 23559680

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Project description:Background and objectivesArteriovenous fistulas are the optimal vascular access type for patients on hemodialysis. However, arteriovenous fistulas are used less frequently in Black than in White individuals. The arteriovenous fistula care continuum comprises a series of sequential steps. A better understanding is needed of where disparities exist along the continuum in order to mitigate racial differences in arteriovenous fistula use.Design, setting, participants, & measurementsUsing Medicare claims data from the United States Renal Data System, longitudinal analyses of patients ≥67 years initiating hemodialysis with a central venous catheter between July 1, 2010 and June 30, 2012 were performed. Three patient cohorts were identified: patients initiating hemodialysis with a catheter (n=41,814), patients with arteriovenous fistula placement within 6 months of dialysis initiation (n=14,077), and patients whose arteriovenous fistulas were successfully used within 6 months of placement (n=7068). Three arteriovenous fistula processes of care outcomes were compared between Blacks and Whites: (1) arteriovenous fistula creation, (2) successful arteriovenous fistula use, and (3) primary arteriovenous fistula patency after successful use.ResultsAn arteriovenous fistula was placed within 6 months of dialysis initiation in 37% of patients initiating dialysis with a catheter. Among the patients with arteriovenous fistula placement, the arteriovenous fistula was successfully used for dialysis within 6 months in 48% of patients. Among patients with successful arteriovenous fistula use, 21% maintained primary arteriovenous fistula patency at 3 years. After adjusting for competing risks, Black patients on hemodialysis were 10% less likely to undergo arteriovenous fistula placement (adjusted subdistribution hazard ratio, 0.90; 95% confidence interval, 0.87 to 0.94); 12% less likely to have successful arteriovenous fistula use after placement (adjusted subdistribution hazard ratio, 0.88; 95% confidence interval, 0.83 to 0.93); and 22% less likely to maintain primary arteriovenous fistula patency after successful use (subdistribution hazard ratio, 0.78; 95% confidence interval, 0.74 to 0.84).ConclusionsLower arteriovenous fistula use among Blacks older than 67 years of age treated with hemodialysis was attributable to each step along the continuum of arteriovenous fistula processes of care.

Project description:Rationale & objectiveThe current clinical guidelines for vascular access do not have specific recommendations for older hemodialysis patients. Our study aimed to determine the association of age with arteriovenous fistula (AVF) placement, maturation, and primary and secondary patency loss among older hemodialysis recipients.Study designRetrospective cohort study.Setting & participantsA US national cohort of incident hemodialysis patients 67 years or older (N = 43,851) assembled from the US Renal Data System.ExposureAge at dialysis initiation.OutcomesAVF placement, maturation, primary patency loss, and abandonment.Analytical approachCause-specific and subdistribution proportional hazards models were used to examine the association of age and AVF outcomes, with kidney transplantation, peritoneal dialysis, and death treated as competing events. Age cutoff was identified by restricted cubic splines. We compared crude and inverse probability-weighted cumulative incidence functions using Gray's test.ResultsAs compared with those aged 67-<77 years, patients 77 years or older had significantly lower probabilities of AVF placement (adjusted cause-specific HR [cHR], 0.96 [95% CI, 0.92-0.99]; adjusted subdistribution HR [sHR], 0.92 [95% CI, 0.89-0.95]; Gray's test P < 0.001) and maturation (adjusted cHR, 0.95 [95% CI, 0.91-0.99]; adjusted sHR, 0.93 [95% CI, 0.90-0.97]; P < 0.001). However, age was not associated with AVF primary (adjusted cHR, 1.05 [95% CI, 1.00-1.11]; adjusted sHR, 1.04 [95% CI, 0.99-1.09]; P = 0.09) or secondary (adjusted cHR, 1.06 [95% CI, 0.94-1.20]; adjusted sHR, 1.05 [95% CI, 0.93-1.18]; P = 0.4) patency loss.LimitationsReliance on administrative claims to ascertain AVF outcomes.ConclusionsThe likelihood of AVF maturation is an important consideration for vascular access planning. Age alone should not be the basis for excluding older dialysis patients from AVF creation because maintenance of fistula patency was not reduced with older age despite a modest reduction in fistula maturation.

Project description:Current guidelines suggest that arteriovenous fistula (AVF) is associated with survival advantage over arteriovenous graft (AVG). However, AVFs often require months to become functional, increasing tunneled dialysis catheter (TDC) use, which can erode the benefit of an AVF. We sought to compare survival in patients with end-stage renal disease after creation of an AVF or AVG in patients starting hemodialysis (HD) with a TDC and to identify patient populations that may benefit from preferential use of AVG over AVF.Using U.S. Renal Data System databases, we identified incident HD patients in 2005 through 2008 and observed them through 2008. Initial access type and clinical variables including albumin levels were assessed using U.S. Renal Data System data collection forms. Attempts at AVF and AVG creation in patients who started HD through a TDC were identified by Current Procedural Terminology codes. We accounted for the effect of changes in access type by truncating follow-up when an additional AVF or AVG was performed. Survival curves were then constructed, and log-rank tests were used for pairwise survival comparisons, stratified by age. Multivariate analysis was performed with Cox proportional hazards regressions; variables were chosen using stepwise elimination. An interaction of access type and albumin level was detected, and Cox models using differing thresholds for albumin level were constructed. The primary outcome was survival.Among the 138,245 patients who started with a TDC and had complete records amenable for analysis, 22.8% underwent AVF creation (mean age ± standard deviation, 68.9 ± 12.5 years; 27.8% mortality at 1 year) and 7.6% underwent AVG placement (70.2 ± 12.0 years; 28.2% mortality) within 3 months of HD initiation; 69.6% remained with a TDC (63.2 ± 15.4 years; 33.8% mortality). In adjusted Cox proportional hazards regression, AVF creation is equivalent to AVG placement in terms of survival (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.93-1.02; P = .349). AVG placement is superior to continued TDC use (HR, 1.54; 95% CI, 1.48-1.61; P < .001). In patients older than 80 years with albumin levels >4.0 g/dL, AVF creation is associated with higher mortality hazard compared with AVG creation (HR, 1.22; 95% CI, 1.04-1.43; P = .013).For patients who start HD through a TDC, placement of an AVF and AVG is associated with similar mortality hazard. Further study is necessary to determine the ideal access for patients in whom the survival advantage of an AVF over an AVG is uncertain.

Project description:BACKGROUND:Arteriovenous fistulas (AVFs) are the preferred form of hemodialysis vascular access, but maturation failures occur frequently, often resulting in prolonged catheter use. We sought to characterize AVF maturation in a national sample of prevalent hemodialysis patients in the United States. STUDY DESIGN:Nonconcurrent observational cohort study. SETTING & PARTICIPANTS:Prevalent hemodialysis patients having had at least 1 new AVF placed during 2013, as identified using Medicare claims data in the US Renal Data System. PREDICTORS:Demographics, geographic location, dialysis vintage, comorbid conditions. OUTCOMES:Successful maturation following placement defined by subsequent use identified using monthly CROWNWeb data. MEASUREMENTS:AVF maturation rates were compared across strata of predictors. Patients were followed up until the earliest evidence of death, AVF maturation, or the end of 2014. RESULTS:In the study period, 45,087 new AVFs were placed in 39,820 prevalent hemodialysis patients. No evidence of use was identified for 36.2% of AVFs. Only 54.7% of AVFs were used within 4 months of placement, with maturation rates varying considerably across end-stage renal disease (ESRD) networks. Older age was associated with lower AVF maturation rates. Female sex, black race, some comorbid conditions (cardiovascular disease, peripheral artery disease, diabetes, needing assistance, or institutionalized status), dialysis vintage longer than 1 year, and catheter or arteriovenous graft use at ESRD incidence were also associated with lower rates of successful AVF maturation. In contrast, hypertension and prior AVF placement at ESRD incidence were associated with higher rates of successful AVF maturation. LIMITATIONS:This study relies on administrative data, with monthly recording of access use. CONCLUSIONS:We identified numerous associations between AVF maturation and patient-level factors in a recent national sample of US hemodialysis patients. After accounting for these patient factors, we observed substantial differences in AVF maturation across some ESRD networks, indicating a need for additional study of the provider, practice, and regional factors that explain AVF maturation.

Project description:Rationale & objectiveComparisons of outcomes between in-center hemodialysis (HD) and peritoneal dialysis (PD) are confounded by selection bias because PD patients are typically younger and healthier and may have received longer predialysis care. We compared first-year survival between what we hypothesized were clinically equivalent groups; namely, patients who initiate maintenance HD using an arteriovenous fistula (AVF) and those selecting PD as their initial modality.Study designObservational, registry-based, retrospective cohort study.Setting & participantsUS Renal Data System data for 5 annual cohorts (2010-2014; n = 130,324) of incident HD with an AVF and incident PD patients.Exposures and predictorsExposure was more than 1 day receiving PD or more than 1 day receiving HD with an AVF. Time at risk for both cohorts was determined for 12 consecutive 30-day segments, censoring for transplantation, loss to follow-up, or end of time. Predictors included patient-level characteristics obtained from Centers for Medicare & Medicaid Services 2728 Form and other data sources.OutcomesPatient survival.Analytical approachUnadjusted and multivariable risk-adjusted HRs for death of HD versus PD patients, averaged over 2010 to 2014, were calculated.ResultsThe HD cohort's average unadjusted mortality rate was consistently higher than for the PD cohort. The HR of HD versus PD was 1.25 (95% CI, 1.20-1.30) in the unadjusted model and 0.84 (95% CI, 0.80-0.87) in the adjusted model. However, multivariable risk-adjusted analyses showed the HR of HD versus PD for the first 90 days was 1.06 (95% CI, 0.98-1.14), decreasing to 0.74 (95% CI, 0.68-0.80) in the 270- to 360-day period.LimitationsResidual confounding due to selection bias inherent in dialysis modality choice and the observational study design. Form 2728 provides baseline data at dialysis incidence alone, but not over time.ConclusionsUS patients receiving HD with an AVF appear to have a survival advantage over PD patients after 90 days of dialysis initiation after accounting for patient characteristics. These findings have implications in the choice of initial dialysis modality and vascular access for patients.

Dataset Information

Candidate gene analysis of arteriovenous fistula failure in hemodialysis patients.

Publications

Candidate gene analysis of arteriovenous fistula failure in hemodialysis patients.

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