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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
ORIGINAL ARTICLE  
Year : 2018  |  Volume : 29  |  Issue : 6  |  Page : 1350-1357
Arteriovenous fistula outcomes in human immunodeficiency virus-positive patients


1 Katz Family Division of Nephrology and Hypertension, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA
2 DeWitt Daughtry Family Department of Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA
3 Division of Nephrology and Hypertension, Albany Medical College, Albany, NY, USA

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Date of Submission11-Dec-2017
Date of Acceptance09-Jan-2018
Date of Web Publication27-Dec-2018
 

   Abstract 

Arteriovenous fistula (AVF) remodeling is an active area of research in vascular biology given the high rates of primary failure, complications, and cost burden for the health-care system. Comorbidities such as diabetes and different types of vascular disease are known to influence AVFs outcomes. However, little is known about the effects of immunosuppression, particularly human immunodeficiency virus (HIV) infection, on AVF primary failure and patency. This retrospective study assessed the impact of HIV infection and T-cell counts on AVF outcomes. Using a retrospective cohort of 495 patients, we compared the risk of AVF primary failure and primary unassisted patency on HIV-positive and nonimmunocompromised individuals using logistic regressions and Cox proportional hazard models. Within the HIV-infected subset (n = 43), we analyzed the association between immunological parameters such as T-cell counts and primary failure. Positive predictors of primary failure were HIV infection [odds ratio (OR) = 3.09, P = 0.002] and history of a previous AVF (OR = 2.18, P = 0.003). However, there was no difference in primary unassisted patency between HIV-positive and negative individuals after excluding primary failure cases. There was no association between T-cell subset counts and AVF outcomes. Our results indicate that HIV-positive individuals have a higher risk of AVF primary failure than nonimmunocompromised patients. However, this increased susceptibility is not explained by the degree of immunosuppression.

How to cite this article:
Duque JC, Martinez L, Tabbara M, Salman LH, Vazquez-Padron RI, Dejman A. Arteriovenous fistula outcomes in human immunodeficiency virus-positive patients. Saudi J Kidney Dis Transpl 2018;29:1350-7

How to cite this URL:
Duque JC, Martinez L, Tabbara M, Salman LH, Vazquez-Padron RI, Dejman A. Arteriovenous fistula outcomes in human immunodeficiency virus-positive patients. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2019 Jan 17];29:1350-7. Available from: http://www.sjkdt.org/text.asp?2018/29/6/1350/248312

Juan C. Duque, Laisel Martinez
These authors contributed equally to the manuscript.


   Introduction Top


Arteriovenous fistulas (AVFs) continue to rank as the best hemodialysis access according to the National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines.[1] However, 30%–50% of AVFs fail to mature adequately to support dialysis therapy,[2],[3] underscoring the need for preventive treatments, and better risk management strategies. Advances in highly active antiretroviral therapy (HAART) have translated into extended life expectancies for patients with human immunodeficiency virus (HIV). Infected individuals make up 1%–2% of the United States end-stage renal disease (ESRD) population,[4] and the prevalence of ESRD in HIV-positive patients continues to rise.[5]

AVFs are particularly recommended in the HIV-positive population[6] due to the high incidence of thrombosis and infections with arteriovenous grafts (AVGs) and tunneled dialysis catheters.[7],[8],[9],[10],[11],[12],[13] An increased frequency of AVG occlusions has also been observed in HIV patients compared to the uninfected population.[7],[8],[9],[14] This higher risk for complications is partly attributed to behavioral factors and preaccess clinical history such as previous/current intravenous drug use and hepatitis B surface antigenemia.[10],[13],[14] However, Mitchell et al reported an increased frequency of AVG infections in HIV-positive patients that appeared to be unrelated to intravenous drug use, CD4 counts, or hypoalbuminemia.[12]

HIV infection is considered an independent risk factor of cardiovascular disease (CVD).[15],[16] A combination of vascular offenders such as dyslipidemia (both HIV associated and HAART related), oxidative stress, inflammation, and hypercoagulability is thought to contribute to endothelial dysfunction,[17],[18] accelerated atherosclerosis,[19],[20] vascular stiff-ness,[21],[22] and increased carotid intima-media thickness.[15],[23] Low CD4+ T-lymphocyte counts predict the severity of PAD,[24] incident CVD events,[16] reduced pulse wave velocity,[25] and the risk of venous thrombosis.[26] Furthermore, experimental AVF models suggest that CD4+ cells are needed for proper venous remodeling.[27]

In light of the above evidence, in this work, we investigate the relationship between immune cell counts in HIV patients and AVF primary failure.

We demonstrate that HIV-positive individuals have a three times higher risk of AVF primary failure than nonimmunocompromised patients. Nonetheless, none of the immuno-logical parameters tested (immune cell counts, T-cell ratios, and viral load) were associated with primary failure in HIV-infected patients.


   Materials and Methods Top


Study participants

This retrospective study included 495 patients over 17 years of age, of whom 43 were HIV positive. All patients underwent AVF creation at Jackson Memorial Hospital or University of Miami Hospital from January 2008 to January 2015. A single surgeon (MT) performed all AVF creation and transposition procedures. The patients’ medical records were reviewed to collect information on demographics, comorbidities, drug treatment at the time of AVF creation, prior vascular access history, and fistula characteristics and outcomes. Immunological parameters including absolute immune cell counts (white blood cells, CD3+, CD4+, CD8+, CD19+, CD16+, and CD56+), percent lymphocytes, CD4/CD8 ratio, and viral load were collected from HIV-positive patients if available. Laboratory results for white blood cells and percent lymphocytes were dated the day of AVF creation, while the rest of the immunological parameters were determined within three months of creation surgery. Patients were excluded from the study if they were lost to follow-up or if the patient underwent a midarm fistula (brachial-brachial) because of the necessity of a graft extension. All sections of the study were performed according to the ethical principles of the Declaration of Helsinki and regulatory requirements at both institutions. The ethics committee and Institutional Review Board at the University of Miami approved the study.

Definitions

Primary failure was defined as an AVF that failed to mature (diameter <6 mm or approximate blood flow <600 mL/min on ultrasound or inability to cannulate for hemodialysis) or that required a radiologic or surgical intervention within three months of creation (one-stage AVF) or transposition (two-stage AVF). Primary patency was defined as the time from creation (one-stage AVF) or transposition (two-stage AVF) until the first radiologic or surgical intervention.


   Statistical Analyses Top


Statistical analyses were performed using XLSTAT (New York, NY, USA). Normally, distributed data were compared using the Student’s t-test and expressed as mean ± standard deviation, while nonnormally distributed values were compared using the Mann-Whitney test and expressed as median and interquartile range. Comparisons between group frequencies were performed using Fisher’s exact test or Chi-square tests. Statistical associations between baseline covariates and primary failure in the overall patient cohort were assessed using multivariate logistic regressions adjusted for age, sex, ethnicity, antiplatelet agent use, comorbidities, AVF type (one vs. two stage), and vascular access history. Logistic regressions of primary failure in the HIV-positive subset were minimally adjusted for ethnicity and history of a previous AVF. Univariate logistic regressions were also used to assess the association between immunological parameters and primary failure. For descriptive statistics and logistic regression analysis, patients with nondetectable viral loads were assigned the lower limit of detection in our laboratories (20 copies/mL). Finally, the effects of baseline covariates on primary unassisted patency were evaluated using multivariate Cox proportional hazards models after excluding primary failure cases. Results were considered statistically significant when P <0.05.


   Results Top


Demographics, clinical, and A VF characteristics of the study population

The entire patient cohort was comprised by 39% females, 37% Hispanics, and 59% non-Hispanic blacks with ages ranging from 18 to 88 years [Table 1]. Most patients were diagnosed with hypertension (98%), while 18% and 55% had coronary artery disease and diabetes, respectively. Twenty-one percent of patients were taking antiplatelet agents and 18% had a history of a previous AVF. HIV-positive patients differed from the nonimmuno-compromised cohort (defined as negative for HIV, lupus, organ transplant, and chemotherapy) in that the former had a lower mean age (43 ± 12 vs. 53 ± 14 years) and were comprised by more non-Hispanic blacks (81% vs. 57%) and fewer Hispanics (16% vs. 39%) than uninfected individuals [Table 1]. In addition, a higher proportion of HIV-positive patients had a history of a previous AVF compared to the nonimmunocompromised population (30% vs. 16%). [Table 2] presents the immunological parameters profile in the HIV-positive cohort within three months of AVF creation. There was a high variability in infection control as evidenced by viral loads ranging from 20 to over 500,000 copies/mL [Table 2]. Only nine of 43 patients (21%) had nondetectable values.
Table 1: Baseline characteristics of the study population.

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Table 2: Immunological parameters in the HIV-positive cohort.

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Statistical associations with arteriovenous fistula outcomes

Primary failure occurred in 51% of HIV-positive patients and 22% of nonimmuno-compromised individuals (P = 0.0001). A multivariate logistic regression adjusting for demographic variables, antiplatelet agents, comorbidities, AVF type, and vascular access history indicated that only HIV infection [odds ratio (OR) = 3.09, P = 0.002] and history of a previous AVF (OR = 2.18, P = 0.003) were associated with primary failure [Table 3]. However, neither ethnicity nor history of a previous AVF was related to AVF outcomes in the HIV-positive cohort [Table 4]. In addition, immunological parameters were not associated with AVF primary failure in HIV patients [Figure 1] and [Table 5].
Table 3: Association between baseline covariates and primary failure in the overall study population by multivariate logistic regression.

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Table 4: Association between select baseline covariates and primary failure in HIV patients by multivariate logistic regression.

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Figure 1: Immunological parameters in HIV-positive patients with arteriovenous fistulas that matured or failed

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Table 5: Association between immunological parameters and primary failure in HIV patients by univariate logistic regressions.

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In terms of primary unassisted patency, non-Hispanics blacks had improved AVF survival (hazard ratio 0.65, P = 0.046) compared to other ethnic groups. No other demographic or clinical covariates were associated with primary patency [Table 6].
Table 6: Association between baseline covariates and primary unassisted patency in the overall study population using a multivariate Cox hazards model.

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   Discussion Top


AVF remodeling continues to be one of the least understood areas in vascular biology. The extensive clinical variability between ESRD patients and the multitude of clinical and behavioral factors that can influence AVF outcomes presents a challenge not only to the study of AVF remodeling but also to the design of better risk management strategies in specific patient populations. Survival of HIV-positive patients with ESRD has improved considerably over the past decade.[28] The expected increase in prevalent ESRD in this patient population[5] and their higher predisposition for vascular access-related complications[7],[8],[9],[10],[11],[12],[14] highlights the need for improving HD access outcomes in this group. This study indicates that HIV-positive patients have a three times higher risk of AVF primary failure than uninfected individuals, but such vulnerability is not explained by the degree of immunosuppression.

The higher frequency of primary failure in the HIV-positive cohort contrasts the results reported by Mitchell et al[12] In the latter retrospective study, the AVF outcomes of 23 HIV-positive individuals were compared to those of 32 uninfected comparators, with approximately 40% of patients in both groups experiencing primary failure. Similar to our cohort, the HIV-infected subgroup in Mitchell et al had an average age close to 40 years old and a higher proportion of black individuals. In contrast, there was a significantly higher prevalence of diabetes in the uninfected controls which could be a confounding factor in their comparisons.[12] Using a larger number of patients in both the HIV-positive and negative groups, which allow for better representation of comorbidities and baseline covariates, we observed significantly better primary failure outcomes in our uninfected cohort (22%) versus the 41% reported in Mitchell et al. It is possible that this is related to the higher numbers of upper-arm AVFs in our study, although this did not help with the elevated frequency of primary failure in the HIV-positive population (51%).

Despite the younger age of the HIV-positive subgroup in the present work compared to the control population, the proportion of patients with a history of a previous AVF was twice as high in the former versus in the uninfected cohort. Both black race and history of a previous AVF have been associated with primary failure in previous studies,[29],[30],[31],[32],[33] and history of a previous AVF is a strong predictor in the present work. However, none of these variables were associated with failure in the HIV-positive population, which suggests that HIV infection is an independent risk factor. We did not collect information on the patients’ social history. Thus, it is not possible to assess whether previous/current intravenous drug use in the present cohort contributed to increased primary failure due to vascular trauma and/or infections. Of note, all AVF creation and transposition procedures in our study were performed by a single surgeon, which minimizes the confounding factors related to the surgical technique and implies an underlying vascular-related problem in HIV-positive patients.

In contrast to the poorer primary failure out-comes in the HIV-infected population, our survival analysis revealed comparable patency of working AVFs from HIV-positive and negative individuals. These results agree with previous retrospective studies[8],[12],[34] and suggest that the main problem with AVFs in HIV-positive patients is the early remodeling period. Results from an experimental AVF model suggested that CD4 cells aid in venous remodeling.[27] Nonetheless, we found no associations between any of the immunological parameters tested and primary failure in HIV patients.

The limitations of this work include a relatively small HIV-positive population, the lack of information on patients’ relevant social history, and the single-center retrospective design of the study. In conclusions, our work reveals that HIV-positive patients are at higher risk of primary failure than uninfected comparators. Given the higher risk of infections and thrombosis with other hemodialysis accesses in the former population,[7],[8],[9],[10],[11],[12],[13] these results underscore the need for understanding and addressing the reasons behind early AVF failure in HIV patients.

Conflict of interest: None declared.

Dr. Juan C. Duque and Mrs. Laisel Martinez contributed equally to the manuscript.

 
   References Top

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Correspondence Address:
Dr. Juan C Duque
Katz Family Division of Nephrology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136
USA
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DOI: 10.4103/1319-2442.248312

PMID: 30588966

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