Gender-Based Utilization and Outcomes of Autogenous Fistulas and Prosthetic Grafts for Hemodialysis Access

Journal Pre-proof Gender Based Utilization and Outcomes of Autogenous Fistulas and Prosthetic Grafts for Hemodialysis Access Isibor J. Arhuidese, MD MPH, Muhammad Faateh, MD, Ryan S. Meshkin, BS, Aurelia Calero, MD, Murray Shames, MD, Mahmoud Malas, MD MHS PII:

S0890-5096(19)30762-9

DOI:

https://doi.org/10.1016/j.avsg.2019.08.083

Reference:

AVSG 4625

To appear in:

Annals of Vascular Surgery

Received Date: 16 August 2018 Revised Date:

4 July 2019

Accepted Date: 1 August 2019

Please cite this article as: Arhuidese IJ, Faateh M, Meshkin RS, Calero A, Shames M, Malas M, Gender Based Utilization and Outcomes of Autogenous Fistulas and Prosthetic Grafts for Hemodialysis Access, Annals of Vascular Surgery (2019), doi: https://doi.org/10.1016/j.avsg.2019.08.083. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Inc.

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Gender Based Utilization and Outcomes of Autogenous Fistulas and Prosthetic

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Grafts for Hemodialysis Access

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Isibor J. Arhuidese MD MPH 1,2; Muhammad Faateh MD2; Ryan S. Meshkin BS3;

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Aurelia Calero MD1; Murray Shames MD1; Mahmoud Malas MD MHS2

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Division of Vascular Surgery, University of South Florida, Tampa, FL Division of Vascular Surgery, Johns Hopkins Medical Institutions, Baltimore, MD Havard Medical School, Boston, MA

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Corresponding Author

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Mahmoud Malas, MD, MHS, FACS Professor of Surgery Chief of Vascular and Endovascular Surgery

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University of California San Diego

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9300 Campus Point Drive,

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La Jolla, CA 92037

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Tel (858) 657-7404

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Fax (858) 657-5033

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Conflicts of interests: None of the authors have any relevant financial disclosures.

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ABSTRACT

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Objective: To evaluate gender-based patterns of utilization and outcomes of

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arteriovenous fistulas (AVF) and grafts (AVG) in a population based cohort of

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hemodialysis (HD) patients.

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Methods: A retrospective analysis of all patients in United States Renal Database

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System who had an AVF or AVG placed for HD access (01/2007-12/2014). Outcomes

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were access maturation, conduit patency, infection and mortality. Chi-square, student t-

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tests, Kaplan-Meier and multivariable Cox regression analyses were employed

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accordingly.

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Results: There were 456693 (57%) males and 341571 (43%) females who initiated HD

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via AVF (16%), AVG (4%) and HD-catheter (80%). There was 30% decrease in odds of

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initiating HD with AVF in females compared to males (aOR: 0.70; 95%CI: 0.69-0.71,

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P<0.001). The use of HD-catheter as a bridge to AVF was 36% higher in females

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compared to males (aOR: 1.36; 95%CI: 1.33-1.39, P<0.001). Pre-emptive AVF

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maturation was 78% for males and 76% for females (p<0.001). The risk adjusted

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analyses showed 7% decrease in AVF maturation comparing females to male (aHR:

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0.93; 95%CI: 0.92-0.95, P<0.001) but no difference in AVG maturation (aHR: 0.99;

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95%CI: 0.97-1.01, P=0.46) After risk adjustment, primary (AVF: aHR-0.87; AVG: aHR-

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0.96), primary-assisted (AVF: aHR-0.84; AVG: aHR-0.97) and secondary (AVF: aHR-

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0.85; AVG: aHR-0.98) patency were lower for females compared to males (all p<0.05).

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Initiation of HD with a catheter and conversion to AVF was associated with lower

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patency in males (aHR:0.29; 95%CI: 0.28-0.29; P<0.001) and females (aHR:0.31;

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95%CI: 0.30-0.31; P<0.001) compared to AVF initiates. Patient survival was higher for

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females compared to males who received AVF (aHR:1.08; 95%CI: 1.07-1.09; P<0.001)

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and AVG (aHR:1.13; 95%CI: 1.11-1.15; P<0.001). Initiation with HD-catheter and

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subsequent conversion to AVF was associated with an increase in mortality for males

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(aHR:1.45; 1.43-1.47; P<0.001) and females (aHR:1.44; 95%CI: 1.44-1.52; P<0.001)

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compared to initiation via AVF. There was no significant difference in severe AVG

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infection comparing females to males (aHR: 1.05; 95%CI: 0.98-1.13; P=0.16).

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Conclusions: Female gender is associated with lower prevalence of preemptive

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AVF’s, higher utilization of catheters as a bridge to AVF and lower patency compared to

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males. There was no difference in access maturation but patient survival was higher for

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females compared to males.

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Keywords: Hemodialysis access, Dialysis, Gender, Arteriovenous fistula, Autogenous

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fistula, Arteriovenous graft, Prosthetic graft, Surgical Outcomes, Healthcare disparities.

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INTRODUCTION

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Hemodialysis (HD) is the most prevalent mode of renal replacement therapy.1

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Current clinical practice guidelines recommend arteriovenous fistula (AVF) as the

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preferred form of HD access in the general population.2,3 It is desirable that patients

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who initiate HD do so with an AVF due to their established benefits relative to

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arteriovenous grafts (AVG) and HD catheters. The benefit that accrues to HD initiation

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with AVF is limited by their maturation time and access failure prior to use. This

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necessitates AVF placement months prior to anticipated HD initiation or bridging with a

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HD catheter until the AVF is matured enough for use. When AV placement is not

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feasible, patients and their providers are left with AVG’s as the next durable option for

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HD access.

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The mode of access used for HD is a significant contributor to survival in these

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patients.4,5 Gender though not modifiable, and its impact on the durability of AV access

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attracts attention given the differences in physiology and provider perception of men

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and women. The objective assessment of access placement practices before and after

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initiation of HD, their maturation times, interventions and the impact these have on

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access durability and patient survival enables the identification of disparities and

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opportunities for outcomes improvement at population levels.

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Prior studies that have evaluated gender based outcomes of AVF and AVG for

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HD access have been limited by small sample sizes, single institutional sources or

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recruitment within randomized trials that exclude subset of patients that contribute to

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real world outcomes.6-11 There is paucity of data on the relative risks between men and

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women published in accordance with reporting standards. The aim of this study is to

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evaluate the utilization of AVF and AVG for HD, access maturation, attainment of

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catheter-free dialysis (CFD), patency, interventions and patient survival in a population

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based cohort of male and female HD patients in the United States. We also estimate the

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risks attributable to prior and persistent use of HD catheters on outcomes within the

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categories of gender.

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METHODS

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A retrospective analysis of all patients in the United State Renal Data System

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(USRDS) who initiated HD between January 1, 2007 and December 31, 2014 was

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performed. The USRDS maintains a prospective database of all ESRD patients

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receiving renal replacement therapy in the United States. Annual reports published

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since 1988 appear at usrds.org and provide information on epidemiology and mortality

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among other parameters.1 The USRDS maintains a robust database on every ESRD

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patient by integrating patient specific data on hospitalization and costs from the Center

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for Medicare and Medicaid service (CMS), Center for Disease Control, United Network

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for Organ Sharing (UNOS) and ESRD networks. The Johns Hopkins institutional review

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board approved this study and the need for individual patient consent was waived.

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The USRDS database contains data on patients’ initial HD access type,

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demographic and medical characteristics obtained via CMS Form 2728, “End Stage

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Renal Disease Medical Evidence Report”. This form is filled out at the treatment facility

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by trained medical personnel. Data on arteriovenous access creation, interventions and

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complications such as stenosis, thrombosis and infection necessitating excision in pre-

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dialysis patients was obtained from a cohort of Medicare beneficiaries who progressed

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to ESRD and were subsequently captured in the USRDS database. Follow-up data was

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obtained from the linked Medicare claims database. The USRDS database also

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contains data on patient mortality, collected from CMS form 2746, “ESRD Death

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Notification Form” that is filled by providers to notify Medicare whenever an ESRD

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patient dies; and matched with the social security death index. The type of

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arteriovenous access created after initiation with a catheter was identified using Current

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Procedural Terminology (CPT) codes for AVF (upper arm cephalic vein transposition:

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36818, upper arm basilica vein transposition: 36819, forearm vein transposition: 36820,

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direct vein to artery anastomoses: 36821, and autogenous graft: 36825) and AVG

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(36830).

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Among patients who initiated HD with a catheter, the total duration of catheter

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exposure was computed as the interval between catheter placement (CPT: 36557,

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36558) and removal (CPT: 36589). The time to CFD was computed as the interval

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between AVF or AVG placement and catheter removal in a patient who initiated HD with

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a catheter. The end of these intervals were identified by catheter-removal not

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associated with a new catheter placement within 7 days; and preceding placement of an

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AVF or AVG. Thus, incorporating all catheter exchanges within the interval. Patency

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was defined in accordance with published standards.12 Primary patency was the interval

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from arteriovenous access creation to the first intervention performed to maintain or

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reestablish patency or access thrombosis. Primary assisted patency was defined as the

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interval from arteriovenous access placement to the first intervention to relieve

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thrombosis.. Secondary patency was defined as the interval from arteriovenous access

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creation to thrombosis/abandonment and subsequent replacement with a new HD

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catheter, AVF or AVG. The following interventions signified the event times used for

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computing the aforementioned patencies: angioplasty (CPT: 35476), stenting (37205,

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75960), thrombectomy (CPT: 36831, 36870) and surgical revision (36832, 36833). We

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also examined the incidence of severe infection necessitating arteriovenous access

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excision (CPT: 35903). AV access was considered to be matured if used for dialysis or

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if the patient achieved catheter free dialysis without placement of a new AVF/AVG.

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Persistent use of HD catheter was defined as initiation of HD with a catheter and

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continuous use without conversion to a fistula or graft. To minimize misclassification

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bias, patients who were documented as recipients of more than one AVF or AVG on the

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same day were excluded (n=966).

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Statistical Methods

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Normality of continuous data was assessed using the Shapiro-Wilk test. Descriptive

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analyses of the study groups were performed using Chi-square and Wilcoxon-rank sum

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test as appropriate. Kaplan-Meier, log rank tests, univariable and multivariable logistic

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and Cox regression analyses were employed to evaluate the outcomes. Relative odds

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and hazard ratios were computed and inferences were made from the risk adjusted

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analyses controlling for demographics, medical characteristics and insurance status.

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The variables included in the multivariable logistic regression were: age, gender, BMI,

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diabetes, hypertension, coronary artery disease, peripheral arterial disease,

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stroke/transient ischemic attack, congestive heart failure, chronic obstructive pulmonary

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disease, functional dependence, cancer, active smoking and insurance status. Patients

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who initiated HD via catheter and subsequently underwent AVF or AVG placement but

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did not achieve CFD were considered to have failed to mature the AVF or AVG. Failure

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was deemed to have occurred on the date a subsequent access (AVF, AVG) was

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placed or by the time the patient was expected to achieve CFD. The expected time to

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CFD was computed based on the probability of attaining CFD per patient

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characteristics. The probability scores were generated using regression models that

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predict attainment of CFD based on patient characteristics in the cohort of patients who

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did and did not achieve CFD. The expected time to CFD for patients who failed to

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achieve CFD was calculated as the median time to CFD for patients within the same

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centile of probability scores. Eligible patients were censored on the date of death,

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kidney transplant, conversion to peritoneal dialysis or at the end of the study (December

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31, 2014). Statistical models were built based on predictive variables from univariate

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analyses, prior literature, guidance of likelihood ratio tests and Akaike’s information

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indices with a goal to achieve model parsimony. Bonferroni corrected comparisons were

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performed to assess for multiple testing within the same dataset. All analyses were

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performed using Stata 14.1 statistical software (StataCorp, College Station, Texas), and

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a p<0.05 was considered statistically significant.

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RESULTS This study comprised 456693 (57.2%) males and 341571 (42.8%) females who

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underwent HD access placement in the study period. Of these, 84597 (18.5%) males

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and 47043 (13.8%) females initiated HD via AVF; 11749 (2.6%) males and 14674

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(4.3%) females initiated HD via AVG; while 360347 (78.9%) males and 279854 (81.9%)

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females initiated HD via catheter. Risk adjusted analyses revealed 30% decrease in

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odds of initiating HD with AVF in females compared to males (aOR: 0.70; 95%CI: 0.69-

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0.71, P<0.001). Trend analyses revealed no significant difference in the absolute and

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risk adjusted proportion of patients who initiated HD via catheter over the years studied.

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Of those who initiated HD via catheter, 98899 (27.5%) males and 72734 (26%) females

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converted to AVF, while 22460 (6.2%) males and 29457 (10.5%) females converted to

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AVG leaving 238988 (66.3%) males and 177663 (63.5%) females who persistently

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received HD via catheters in the study period. Consequently, the prevalence of catheter

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as a bridge to AVF was higher among females (62.4%) compared to males (55.7%;

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p<0.001). The risk adjusted odds of HD catheter use as a bridge to AVF was 36%

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higher in females compared to males (aOR: 1.36; 95%CI: 1.33-1.39, P<0.001). The

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distribution of patient characteristics is shown in table 1. Mean follow-up was 28.3

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months (SD: 22.6; Median: 22.8; IQR: 9.4-42.5) for males and 28.8 months (SD: 22.8;

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Median: 23.4; IQR: 9.7-43.4) for females (p<0.001).

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Pre-emptive access maturation rate comparing males vs. females was 78 vs

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75.5% (p<0.001) for AVF recipients and 83.3 vs 84% for AVG recipients (p=0.47).

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Among patients who initiated dialysis via catheter, the median interval from initiation

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with catheter to permanent access creation was 13.7 weeks for males and 14.1 weeks

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for females (p<0.001). The incidence of CFD within 12 months in patients who initiated

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HD with a catheter comparing males versus females was 80.1 vs 79.7% (p<0.001) for

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AVF recipients and 77.5 vs 77.9% (p=0.38) for AVG recipients (figure 1). The median

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interval between AV access placement and use for males vs females was 86 vs 82 days

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for AVF recipients (p<0.001) and 41 days for male and female AVG recipients (p=0.55).

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The risk adjusted analyses showed 7% decrease in AVF maturation comparing females

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to male (aHR: 0.93; 95%CI: 0.92-0.95, P<0.001) but no difference in AVG maturation

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(aHR: 0.99; 95%CI: 0.97-1.01, P=0.46). The median duration of HD catheter exposure

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among patients who persistently dialyzed via HD catheter was 16.1 months (IQR: 4.8-

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37.6) for males and 15.3 months (IQR: 4.5-36.8) for females (p<0.001).

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Comparing males vs females, the unadjusted Kaplan-Meier estimates of primary

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patency at 5 years was 23 vs. 18% (p<0.001) for AVF and 11 vs. 9% (p<0.001) for AVG

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(figure 2). Primary assisted patency at 5 years comparing males vs. females was 40 vs.

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31% (p<0.001) for AVF and 19 vs. 17% (p<0.001) for AVG (tables 2 & 3). Secondary

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patency at 5 years comparing males vs. females was 50 vs. 41% (p<0.001) for AVF and

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37 vs. 34% (p<0.001) for AVG (figure 3). The mean number of interventions required to

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achieve these patency rates for males vs. females was 2.3 vs 2.6 for AVF recipients

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(p<0.001) and 4.5 vs 4.8 for AVG recipients (p<0.001). The proportion of male vs

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female patients who required surgical or endovascular interventions to achieve these

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patency rates was 38.2 vs 41.2% for AVF (p<0.001) and 53.1 vs 56.7% for AVG

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(p<0.001). The risk adjusted analyses showed 13-15% reduction in primary, primary

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assisted and secondary patency for females compared to males who received AVF; and

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2-3% reduction in primary, primary assisted and secondary patency for females

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compared to males who received AVG (table 4). Initiation with a catheter and

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subsequent conversion to AVF was associated with a decrease in AVF patency for

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males (aHR: 0.29; 95%CI: 0.28-0.29; P<0.001) and females (aHR: 0.31; 95%CI: 0.30-

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0.31; P<0.001) compared to initiation of HD via AVF. Primary patency was significantly

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higher for AVF relative to AVG within strata of male (aHR: 1.29; 95%CI: 1.27-1.31;

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P<0.001) and female (aHR: 1.18; 95%CI: 1.16-1.19; P<0.001) patients. Primary patency

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was lower for upper arm basilic vein transposition (aHR: 0.94; 95%CI: 0.92-0.95;

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P<0.001), forearm any vein transposition (aHR: 0.87; 95%CI: 0.85-0.90; P<0.001),

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fistula via direct vein to artery anastomosis (aHR: 0.90; 95%CI: 0.89-0.92; P<0.001) and

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autogenous graft AV access (aHR: 0.89; 95%CI: 0.86-0.91; P<0.001) relative to

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cephalic vein transposition in males and females.

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The prevalence of AVG infection necessitating excision was 4 vs 4.3% (p=0.09)

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for males vs females respectively. There was no significant difference in adjusted

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hazards of severe AVG infection comparing females to males (aHR: 1.05; 95%CI: 0.98-

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1.13; P=0.16).

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Absolute all-cause mortality comparing males vs. females was 42.3(p=0.88) for

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male and female AVF recipients and 52.7 vs 50.2% for AVG recipients (p<0.001).

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Kaplan-Meier estimates of patient survival at 5 years for males vs. females was 42 vs

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42% (p<0.001) for AVF and 31 vs 34% (p<0.001) for AVG (figure 4). The risk adjusted

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analyses showed 8% and 13% increase in patient survival for females compared to

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males in the AVF (aHR: 1.08; 95%CI: 1.07-1.09; P<0.001) and AVG sub cohorts (aHR:

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1.13; 95%CI: 1.11-1.15; P<0.001) respectively. Risk adjusted mortality was 30% higher

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for AVG relative to AVF within strata of males (aHR: 1.30; 95%CI: 1.27-1.32; P<0.001)

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and 23% higher within the strata of female patients (aHR: 1.23; 95%CI: 1.21-1.25;

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P<0.001). Initiation with a catheter and subsequent conversion to AVF was associated

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with a 45% increase in mortality for males (aHR: 1.45; 95%CI: 1.43-1.47; P<0.001) and

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44% increase in mortality for females (aHR: 1.44; 95%CI: 1.42-1.47; P<0.001)

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compared to initiation via AVF. Initiation of HD with catheter and its persistent use

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compared to initiation with AVF was associated with a 78% increase in the risk adjusted

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mortality in males (aHR: 1.78; 95%CI: 1.75-1.80; P<0.001) and 93% increase in females

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(aHR: 1.93; 95%CI: 1.90-1.96; P<0.001).

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DISCUSSION In this population based study, we have shown lower prevalence of preemptive

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AVF placement for females compared to males and higher prevalence of catheters as a

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bridge to AVF among females compared to males. Risk adjusted patient survival was

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higher for females compared to males. AVF maturation and AV access patency were

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consistently lower for females compared to males. However, there was no significant

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difference in AVG infection warranting excision for females compared to males.

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It has been argued that females have smaller veins when compared to males

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and this might account for the higher prevalence of AVG’s in females.6-11 However, the

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30% decrease in the preemptive placement AVF to the disfavor of females deserves

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attention, in depth evaluation of the underpinnings of this practice and redress given the

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fact that these females eventually get AVF’s albeit after potentially avoidable catheter

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exposure. This study revealed 36% risk adjusted increase in utilization of HD catheters

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as a bridge to AVF. Concerted efforts by primary care providers, nephrologists and AV

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access surgeons will be helpful in addressing this disparity. This study shows the

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deleterious impact of HD initiation via catheters on access durability and patient

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survival. Indeed, the lower utilization of AVF’s in females compared to males is a

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potential cause of the disproportionately higher rate of access related hospitalizations in

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females that has been reported previously.13 Frequent access related hospitalizations

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bear a negative impact on patient and system resources as well as quality of life. Our

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results show that over 75% of preemptively placed AVF were utilized for HD. This high

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proportion of successful pre-emptive AVF’s supports the need for AVF placement prior

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to initiation of HD in females and indeed all patients. Nonetheless, further improvement

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in efficacy of preemptively placed AVF’s is desirable.

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The longer interval to CFD compared to maturation times in this study is likely

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due to the fact that catheters are not removed until satisfactory HD via the AV access is

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achieved. The interval between initiation of HD via catheter and permanent access

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placement; and the longer time to CFD relative to maturation time that we have shown

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represent avoidable exposure to the deleterious impact of hemodialysis catheters.

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Avoiding catheter use and limiting these prolonged periods of catheter exposure are

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potent opportunities for outcomes improvement at population levels.

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The arteriovenous access patency rates reported in in this large, national study

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are consistent with those from other studies which reported that overall median patency

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for AVF ranged from 3-5 years, while that of AVG was 1-2 years.8,9,14-20 Despite the

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lower access patency in females, they enjoyed better survival compared to males after

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risk adjustment. Hence, the need for durable access to accompany their high survival;

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and a proactive disposition to surveillance and intervention in female patients with

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borderline performing AV accesses.. It might be expected that patients who enjoy better

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AV access patency also enjoy better patient survival. This is not always the case as

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shown in this study. The gender based differences in these outcomes exemplify the

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important role population studies such as this play in delineating associations between

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sub groups of patients and outcomes. This study shows pre-emptive AVF’s outperform

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catheters as a bridge to permanent access and AVG’s irrespective of gender.

294 295

The high utilization of HD catheters at incident hemodialysis noted in this study and others mirrors the rationale for national improvement programs aimed at decreasing

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HD catheter use.21 There was no significant difference in the absolute and risk adjusted

297

proportions of patients who initiated HD via catheter over time. Reversing the high

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utilization of HD catheters at incident HD and their persistent use thereafter, remain

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opportunities for outcomes improvement at population levels. Our assessment of

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arteriovenous access-related interventions and complications in pre-dialysis patients

301

was based on a cohort of Medicare beneficiaries who progressed to ESRD. This study

302

does not include non-Medicare pre-dialysis patients as well as those who received

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preemptive arteriovenous access but did not progress to end stage renal disease.

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Nonetheless, the cohort of patients who progress to HD is a closed one and the

305

proportions of patients who utilized their preemptive AVF or AVG at HD is informative.

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Due to data coding constraints, our report of severe infections excludes those that did

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not require excision, therefore underestimating the overall incidence of AV access-

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related infections. The incidence of such severe infections leading to loss of access is

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an important outcome to report. This study is limited in its retrospective nature and it

310

does not offer a randomized comparison of males versus females. It is also limited in

311

the granularity of clinical details available in the USRDS. We cannot account for factors

312

that might impact patency such as vein size, medication use, biologic or synthetic graft

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subtypes and the precise cause of access failure or death. We are unable to

314

differentiate planned second stage revisions versus those performed for failed or failing

315

accesses. The strengths of this study include its robust sample size, made possible by

316

the magnitude and comprehensive nature of the USRDS, as well as its longitudinal

317

design. Due to the large sample size, the probability that the differences observed

318

between the groups are due to chance is small. Hence, the small p-values. This lays

17

319

emphasis on the clinical significance of the magnitude of relative differences observed.

320

This population-based study comprehensively delineates clinically relevant outcomes

321

associated with HD access between men and women; and we have revealed a disparity

322

in pre-emptive AVF placement and utilization of HD catheters as a bridge to AVF in

323

women relative to men. These results render support for interventions aimed at

324

addressing these disparities; and they inform the expectations of patients and their

325

providers when considering options for HD access.

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CONCLUSION

326 327

Female gender is associated with lower prevalence of preemptive AVF’s, higher

328

utilization of catheters as a bridge to AVF and lower patency compared to males. There

329

was no difference in access maturation but patient survival was higher for females

330

compared to males. The need remains to improve preemptive AVF placement in males

331

and females; and address the gender based disparities that we have shown, given the

332

access and patient survival related advantages associated with pre-emptive AVF use

333

irrespective of gender.

334 335 336 337

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REFERENCES

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1. US Renal Data System (2015). USRDS 2015 annual data report: Atlas of chronic

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kidney disease and end-stage renal disease in the united states.

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https://www.usrds.org/2015/view. Updated 2015. Accessed 09/09, 2016.

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2. Vascular Access Work Group. Clinical practice guidelines for vascular access. Am J

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Kidney Dis. 2006;48 Suppl 1:S248-73.

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3. NKF-K I. DOQI clinical practice guidelines for vascular access: Update 2000. Am J

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Kidney Dis. 2001;37(1 Suppl 1):S137-81.

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4. Arhuidese IJ, Obeid T, Hicks C, Qazi U, Botchey I, Zarkowsky DS, et al. Vascular

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395 22

TABLE

396 397

Table 1: Characteristics of male and female patients

398 Characteristic

AVF

AVG

Catheter Persistent

N=303273

N=78340

N=416651

Males

Females

183496

119777

(60.5%)

(39.5%)

65 (54-75)

67 (56-75)

White

60.4

55.6

Black

25.9

30

Age, median (IQR)

P-value

<0.001

Males

Females

34209

44131

(43.7%)

(56.3%)

67 (56-77)

68 (58-77)

48.2

45.1

39.4

42.6

P-value

<0.001

Males

Females

238988

177663

(57.4%)

(42.6%)

62 (51-73)

64 (53-75)

58.3

54.4

26.1

29.9

P-value

<0.001

Race:

<0.001

<0.001

<0.001

Hispanic

8.2

8.1

7.1

6.9

10.2

9.8

Other

5.5

6.3

5.3

5.3

5.5

5.9

27 (24-32)

29 (24-35)

<0.001

27 (23-31)

29 (24-35)

<0.001

27 (23-32)

28 (23-34)

<0.001

Diabetes

58.2

62.9

<0.001

59.3

65

<0.001

56

59.3

<0.001

Hypertension

87.3

87.9

<0.001

86

87.8

<0.001

82.3

84

<0.001

Coronary artery

20.7

17.7

<0.001

20.9

18.5

<0.001

18.7

16.2

<0.001

13.6

11.3

<0.001

15.4

12.7

<0.001

13.1

11.4

<0.001

Body Mass Index, median (IQR)

disease Peripheral artery disease

23

Stroke/transient

8.8

9.1

0.005

11.2

11.2

0.87

8.4

9.2

<0.001

29.7

31.4

<0.001

32.6

33.9

<0.001

30.8

32.8

<0.001

8.9

9.3

<0.001

9.8

9.5

0.12

9.4

9.8

<0.001

Cancer

7.5

5.7

<0.001

8.0

6.1

<0.001

8.4

7.2

<0.001

Immobility

4.5

6.2

<0.001

7.4

8.7

<0.001

7.7

10.4

<0.001

Active smoking

6.7

4.9

<0.001

6.8

4.6

<0.001

7.1

5.0

<0.001

Prior hemodialysis

53.9

60.7

<0.001

65.7

66.8

<0.001

-

-

ischemic attack Congestive heart failure Chronic obstructive pulmonary disease

catheter use

399 400 401 402

Column values are proportions except otherwise stated

403 404 405 406

24

407

Table 2: Kaplan-Meier estimates of primary patency, primary assisted patency, secondary patency and survival for male

408

and female patients who received autogenous fistulas.

409 Outcome

Primary

Gender

Males

1 Year

2 years

3 years

4 years

5 years

6 years

7 years

% (95% CI)

% (95% CI)

% (95% CI)

% (95% CI)

% (95% CI)

% (95% CI)

% (95% CI)

46.2 (46.0-46.4)

37.7 (37.5-37.9)

31.6 (31.4-31.9)

23.3 (23.0-23.6)

20.8 (20.5-

18.7 (18.3-

21.1)

19.1)

15.5 (15.1-

13.7 (13.2-

15.8)

14.1)

36.7 (36.3-

33.5 (33.0-

37.1)

34.0)

28.3 (27.9-

25.5 (24.9-

28.8)

26.0)

26.9 (26.6-27.1)

patency Females

Primary assisted patency

Males

Females

Secondary

Males

37.5 (37.2-37.7)

59.2 (59.0-59.4)

49.7 (49.4-50)

65.4 (65.2-65.6)

29.7 (29.4-30)

53.2 (53.0-53.5)

43.4 (43.1-43.7)

60.8 (60.5-61.0)

24.5 (24.2-24.8)

48.4 (48.2-48.7)

38.9 (38.6-39.3)

57.0 (56.7-57.3)

20.5 (20.2-20.8)

44.0 (43.7-44.3)

34.9 (34.6-35.2)

53.4 (53.1-53.6)

17.7 (17.3-18)

40.1 (40--40.4)

31.4 (31.0-31.7)

49.9 (49.6-50.2)

patency Females

Patient

Males

57.3 (57.0-57.6)

83.2 (83.0-83.3)

52.0 (51.7-52.3)

70.6 (70.4-70.9)

48.1 (47.7-48.4)

59.5 (59.3-59.8)

44.4 (44.1-44.8)

49.9 (49.6-50.2)

41.0 (40.6-41.4)

41.6 (41.3-41.9)

survival Females

83.7 (83.5-83.9)

71.5 (71.2-71.8)

60.6 (60.2-60.9)

50.6 (50.2-50.9)

42.1 (41.7-42.5)

46.7 (46.3-

43.8 (43.3-

47.1)

44.3)

38.0 (37.6-

34.8 (34.3-

38.5)

35.5)

34.6 (34.3-

28.5 (28.1-

35.0)

28.9)

34.7 (34.3-

28.8 (28.2-

35.1)

29.3)

P-value

<0.001

<0.001

<0.001

<0.001

410 411 412

25

413

Table 3: Kaplan-Meier estimates of primary patency, primary assisted patency, secondary patency and survival for male

414

and female patients who received prosthetic grafts.

Outcome

Gender

1 Year

2 years

3 years

4 years

5 years

6 years

7 years

P-value

% (95% CI)

% (95% CI)

% (95% CI)

% (95% CI)

% (95% CI)

% (95% CI)

% (95% CI)

Primary

Males

31.8 (31.3-32.3)

21.2 (20.7-21.7)

15.8 (15.3-16.3)

12.6 (12.1-13.1)

10.8 (10.2-11.3)

9.8 (9.2-10.3)

8.9 (8.3-9.5)

patency

Females

30.0 (29.5-30.4)

18.9 (18.4-19.3)

13.5 (13.1-13.9)

10.9 (10.5-11.3)

9.3 (8.9-9.7)

8.3 (7.9-8.7)

7.6 (7.2-8.1)

Primary assisted patency

Males

42.3 (41.8-42.9)

32.0 (31.4-32.5)

26.1 (25.5-26.6)

22.1 (21.5-22.7)

19.1 (18.4-19.7)

16.9 (16.2-

14.9 (14.0-

17.7)

15.8)

14.6 (14.0-

13.0 (12.3-

15.2)

13.7)

Females

Secondary

Males

41.0 (40.5-41.5)

59.2 (58.6-59.7)

29.9 (29.4-30.4)

51.1 (50.6-51.7)

23.6 (23.1-24.0)

45.6 (44.9-46.2)

19.8 (19.3-20.3)

40.8 (40.1-41.5)

17.2 (16.6-17.7)

37.1 (36.3-37.9)

patency Females

Patient

Males

58.4 (57.9-58.9)

74.5 (74.1-75.0)

49.6 (49.1-50.1)

59.4 (58.8-59.9)

43.5 (42.9-44.1)

47.9 (47.2-48.5)

38.4 (37.8-39.0)

38.7 (38.0-39.3)

33.7 (33.0-34.4)

31.1 (30.4-31.8)

survival Females

78.1 (77.6-78.5)

63.8 (63.3-64.3)

52.1 (51.5-52.6)

41.9 (41.3-42.5)

33.8 (33.2-34.4)

33.1 (32.1-

29.6 (28.3-

34.0)

30.9)

29.8 (29.0-

27.1 (26.1-

30.7)

28.2)

25.3 (24.6-

20.6 (19.8-

26.0)

21.4)

27.5 (26.9-

22.4 (21.6-

28.2)

23.1)

<0.001

<0.001

<0.001

<0.001

26

415

Table 4: Long term outcome comparing females to males who received autogenous

416

fistulas and prosthetic grafts: Multivariable Cox regression analysis Outcome

Autogenous fistula

Prosthetic graft

HR (95%CI)

P-value

HR (95%CI)

P-value

Primary patency

0.87 (0.86-0.88)

<0.001

0.96 (0.95-0.98)

<0.001

Primary assisted

0.84 (0.83-0.84)

<0.001

0.97 (0.95-0.98)

<0.001

Secondary patency

0.85 (0.84-0.86)

<0.001

0.98 (0.96-0.99)

0.028

Patient survival

1.08 (1.07-1.09)

<0.001

1.13 (1.11-1.15)

<0.001

patency

417

HR: Hazards ratio, CI: confidence interval

418

Variables included in the multivariable analyses: age, race, BMI, hypertension, coronary

419

artery disease, congestive heart failure, chronic obstructive pulmonary disease,

420

functional dependence, cancer, active smoking.

27

Figures Legends

421 422

Figure 1: Catheter free dialysis

423

Figure 2: Primary patency

424

Figure 3: Secondary patency

425

Figure 4: Patient survival

28