International Comparisons of Native Arteriovenous Fistula Patency and Time to Becoming Catheter-Free: Findings From the Dialysis Outcomes and Practice Patterns Study (DOPPS).

RATIONALE & OBJECTIVE: Optimizing vascular access use is crucial for long-term hemodialysis patient care. Because vascular access use varies internationally, we examined international differences in arteriovenous fistula (AVF) patency and time to becoming catheter-free for patients receiving a new AVF. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 2,191 AVFs newly created in 2,040 hemodialysis patients in 2009 to 2015 at 466 randomly selected facilities in the Dialysis Outcomes and Practice Patterns Study (DOPPS) from the United States, Japan, and EUR/ANZ (Belgium, France, Germany, Italy, Spain, Sweden, United Kingdom, Australia, and New Zealand). PREDICTORS: Demographics, comorbid conditions, dialysis vintage, body mass index, AVF location, and country/region. OUTCOMES: Primary/cumulative AVF patency (from creation), primary/cumulative functional patency (from first use), catheter dependence duration, and mortality. ANALYTICAL APPROACH: Outcomes estimated using Cox regression. RESULTS: Across regions, mean patient age ranged from 61 to 66 years, with male preponderance ranging from 55% to 66%, median dialysis vintage of 0.3 to 3.2 years, with 84%, 54%, and 32% of AVFs created in the forearm in Japan, EUR/ANZ, and United States, respectively. Japan displayed superior primary and cumulative patencies due to higher successful AVF use, whereas cumulative functional patency was similar across regions. AVF patency associations with age and other patient characteristics were weak or varied considerably between regions. Catheter-dependence following AVF creation was much longer in EUR/ANZ and US patients, with nearly 70% remaining catheter dependent 8 months after AVF creation when AVFs were not successfully used. Not using an arteriovenous access within 6 months of AVF creation was related to 53% higher mortality in the subsequent 6 months. LIMITATIONS: Residual confounding. CONCLUSIONS: Our findings highlight the need to reevaluate practices for optimizing long-term access planning and achievable AVF outcomes, especially AVF maturation. New AVFs that are not successfully used are associated with long-term catheter exposure and elevated mortality risk. These findings highlight the importance of selecting the best access type for each patient and developing effective clinical pathways for when AVFs fail to mature successfully.

Medicare Costs Associated With Arteriovenous Fistulas Among US Hemodialysis Patients.

BACKGROUND: An arteriovenous fistula (AVF) is the recommended vascular access for hemodialysis (HD). Previous studies have not examined the resources and costs associated with creating and maintaining AVFs. STUDY DESIGN: Retrospective observational study. SETTING & PARTICIPANTS: Elderly US Medicare patients initiating hemodialysis therapy during 2010 to 2011. PREDICTOR: AVF primary and secondary patency and nonuse in the first year following AVF creation. OUTCOMES: Annualized vascular access costs per patient per year. RESULTS: Among patients with only a catheter at HD therapy initiation, only 54% of AVFs were successfully used for HD, 10% were used but experienced secondary patency loss within 1 year of creation, and 83% experienced primary patency loss within 1 year of creation. Mean vascular access costs per patient per year in the 2.5 years after AVF creation were $7,871 for AVFs that maintained primary patency in year 1, $13,282 for AVFs that experienced primary patency loss in year 1, $17,808 for AVFs that experienced secondary patency loss in year 1, and $31,630 for AVFs that were not used. Similar patterns were seen among patients with a mature AVF at HD therapy initiation and patients with a catheter and maturing AVF at HD therapy initiation. Overall, in 2013, fee-for-service Medicare paid $2.8 billion for dialysis vascular access-related services, ∼12% of all end-stage renal disease payments. LIMITATIONS: Lack of granularity with certain billing codes. CONCLUSIONS: AVF failure in the first year after creation is common and results in substantially higher health care costs. Compared with patients whose AVFs maintained primary patency, vascular access costs were 2 to 3 times higher for patients whose AVFs experienced primary or secondary patency loss and 4 times higher for patients who never used their AVFs. There is a need to improve AVF outcomes and reduce costs after AVF creation.

International Differences in the Location and Use of Arteriovenous Accesses Created for Hemodialysis: Results From the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Vascular access practice is strongly associated with clinical outcomes. There is substantial international variation in the use of arteriovenous fistulas (AVFs) and grafts (AVGs), as well as AVF maturation time and location. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Hemodialysis patients participating in the prospective Dialysis Outcomes and Practice Patterns Study (DOPPS) from the United States, Japan, and Europe/ANZ (Belgium, France, Germany, Italy, Spain, Sweden, United Kingdom, Australia, and New Zealand), including 3,850 patients receiving 4,247 new AVFs and 842 patients receiving 1,129 new AVGs in 2009 to 2015. AVF location trends were based on 38,868 AVFs recorded in DOPPS 1 to 5 cross-sections (1996-2015). PREDICTORS: Demographics, comorbid conditions, dialysis vintage, body mass index, facility percentage AVF use, median blood flow rate, and AVF location. OUTCOMES: AVF location; successful AVF/AVG use (≥30 days of continuous use); time-to-first successful AVF/AVG use (maturation). RESULTS: During DOPPS 1 to 5, the percentage of AVFs created in the lower arm was consistently ≥93% in Japan and 65% to 77% in Europe/ANZ, but in the United States, this value declined from 70% (DOPPS 1) to 32% (DOPPS 5). Patient characteristics associated with AVF location differed by region. Successful AVF use was 87% in Japan, 67% in Europe/ANZ, and 64% in the United States, whereas successful AVG use was 86%, 75%, and 78%, respectively. Successful AVF use was greater for upper- versus lower-arm AVFs in the United States, with little difference in Europe/ANZ and the opposite pattern in Japan. Median time until first successful AVF use was 10 days in Japan, 46 days in Europe/ANZ, and 82 days in United States; until first successful AVG use: 6, 24, and 29 days, respectively. LIMITATIONS: Potential measurement error related to chart data abstraction in multiple hemodialysis facilities. CONCLUSIONS: Large international differences exist in AVF location, predictors of AVF location, successful use of AVFs, and time to first AVF/AVG use, challenging what constitutes best practice. The large US shift from lower- to upper-arm AVFs raises serious concerns about long-term health implications for some patients and how policies and practices aimed at increasing AVF use have affected AVF placement location.

Vessel Mapping for Dialysis Access Planning.

The population of patients with end-stage renal disease (ESRD) in the United States is progressively increasing, with hemodialysis (HD) as the major mode of renal replacement therapy. National guidelines recommend increasing the use of arteriovenous fistulae (AVF) in both incident and prevalent hemodialysis patients. Pre-operative vascular mapping prior to the surgical creation of an AVF is now considered standard of care and may be helpful in achieving these goals. This manuscript focuses on the advantages and limitations of the various imaging techniques currently available for vessel mapping including physical examination, ultrasonography, angiography (iodinated contrast vs. CO2 ), and magnetic resonance angiography (MRA), with specific suggestions for clinical use.

Health status as a potential mediator of the association between hemodialysis vascular access and mortality.

BACKGROUND: It is unknown whether the selection of healthier patients for arteriovenous fistula (AVF) placement explains higher observed catheter-associated mortality among elderly hemodialysis patients. METHODS: From the United States Renal Data System 2005-2007, we used proportional hazard models to examine 117 277 incident hemodialysis patients aged 67-90 years for the association of initial vascular access type and 5-year mortality after accounting for health status. Health status was defined as functional status at dialysis initiation and number of hospital days within 2 years prior to dialysis initiation. RESULTS: Patients with catheter alone had more limited functional status (25.5 versus 10.8% of those with AVF) and 3-fold more prior hospital days than those with AVF (mean 18.0 versus 5.4). In the unadjusted model, the likelihood of death was higher for arteriovenous grafts (AVG) {Hazard ratio (HR) 1.20 [95% CI (1.16-1.25)], catheter plus AVF [HR 1.34 (1.31-1.38)], catheter plus AVG [HR 1.46 (1.40-1.52)] and catheter only [HR 1.95 (1.90-1.99)]}, compared with AVF (P < 0.001). The association attenuated -23.7% (95% CI -22.0, -25.5) overall (AVF versus all other access types) after adjusting for the usual covariates (including sociodemographics, comorbidities and pre-dialysis nephrology care) {AVG [HR 1.21 (1.17-1.26)], catheter plus AVF [HR 1.27 (1.24-1.30)], catheter plus AVG [HR 1.38 (1.32-1.43)] and catheter only [HR 1.69 (1.66-1.73)], P < 0.001}. Additional adjustment for health status further attenuated the association by another -19.7% (-18.2, -21.3) overall but remained statistically significant . CONCLUSIONS: The observed attenuation in mortality differences previously attributed to access type alone suggests the existence of selection bias. Nevertheless, the persistence of an apparent survival advantage after adjustment for health status suggests that AVF should still be the access of choice for elderly individuals beginning hemodialysis until more definitive data eliminating selection bias become available.

Identification of inflammatory clusters in long-COVID through analysis of plasma biomarker levels.

Mechanisms underlying long COVID remain poorly understood. Patterns of immunological responses in individuals with long COVID may provide insight into clinical phenotypes. Here we aimed to identify these immunological patterns and study the inflammatory processes ongoing in individuals with long COVID. We applied an unsupervised hierarchical clustering approach to analyze plasma levels of 42 biomarkers measured in individuals with long COVID. Logistic regression models were used to explore associations between biomarker clusters, clinical variables, and symptom phenotypes. In 101 individuals, we identified three inflammatory clusters: a limited immune activation cluster, an innate immune activation cluster, and a systemic immune activation cluster. Membership in these inflammatory clusters did not correlate with individual symptoms or symptom phenotypes, but was associated with clinical variables including age, BMI, and vaccination status. Differences in serologic responses between clusters were also observed. Our results indicate that clinical variables of individuals with long COVID are associated with their inflammatory profiles and can provide insight into the ongoing immune responses.

Accumulation of retained nonfunctional arteriovenous grafts correlates with severity of inflammation in asymptomatic ESRD patients.

BACKGROUND: The contribution of multiple retained nonfunctional arteriovenous grafts (AVGs) to the burden of chronic inflammation in chronic hemodialysis patients has not been well studied. Here, we sought to evaluate the association between plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and albumin and the number of retained nonfunctional AVGs. METHODS: This cross-sectional study enrolled 91 prevalent patients undergoing in-center hemodialysis without evidence of infection or inflammation. A baseline blood sample was obtained at study enrollment. A general linear model (GLM) was used to compare levels of biomarkers of systemic inflammation across groups defined by the number of retained, nonfunctional AVGs. RESULTS: A total of 43 patients had one or more retained thrombosed AVG and had significantly greater plasma log-CRP levels compared with patients without a previous AVG (P= 0.036), regardless of the current AV access type. Using a GLM, we found that for every additional retained thrombosed AVG, plasma log-CRP, log-IL-6 and TNF-alpha concentrations increased significantly by 0.30 mg/L (P= 0.011), 0.18 pg/mL (P= 0.046) and 0.72 pg/mL (P= 0.046), respectively, following adjustment. CONCLUSIONS: Hence, the severity of inflammation increases with the number of retained nonfunctional AVG's, suggesting that AVG accumulation may contribute to the cardiovascular morbidity and mortality associated with chronic inflammation in asymptomatic end-stage renal disease (ESRD) patients. Further study is indicated to determine whether patients with one or more thrombosed, retained AVG may benefit from periodic screening with CRP monitoring to identify those patients who may benefit from AVG resection.

Cardiovascular implantable electronic device leads in CKD and ESRD patients: review and recommendations for practice.

Cardiovascular implantable electronic devices (CIEDs) are frequently utilized for management of cardiac dysrhythmias in patients with chronic kidney disease or end-stage renal disease receiving hemodialysis. The survival benefit from use of implantable cardioverter defibrillators in patients with CKD or ESRD is not as clear as in the general population, particularly when used for primary prevention of sudden cardiac death. Transvenous CIED leads are associated with central vein stenosis resulting in significant adverse consequences for existing or future arteriovenous access. Venous hypertension from CIED lead-related central vein stenosis is a challenging clinical problem and may require repeated percutaneous interventions, replacement of the CIED, or creation of alternative arteriovenous access. Infections associated with transvenous CIED leads are more frequent and associated with worse outcomes in patients with renal disease. Epicardial CIED leads or other nontransvenous devices may reduce complications of both central venous stenosis and endovascular infection in these vulnerable patients. Consensus recommendations are offered for avoidance and management of complications arising from the use of CIEDs and arteriovenous hemodialysis access.

ASDIN white paper: Management of cephalic arch stenosis endorsed by the American Society of Diagnostic and Interventional Nephrology.

Brachiocephalic arteriovenous fistulas (AVF) makeup approximately one third of prevalent dialysis vascular accesses. The most common cause of malfunction with this access is cephalic arch stenosis (CAS). The accepted requirement for treatment of a venous stenosis lesion is ⩾50% stenosis associated with hemodynamically abnormalities. However, the correlation between percentage stenosis and a clinically significant decrease in access blood flow (Qa) is low. The critical parameter is the absolute minimal luminal diameter (MLD) of the lesion. This is the parameter that exerts the key restrictive effect on Qa and results in hemodynamic and functional implications for the access. CAS is the result of low wall shear stress (WSS) resulting from the effects of increased blood flow and the unique anatomical configuration of the CAS. Decrease in WSS has a linear relationship to increased blood flow velocity and neointimal hyperplasia exhibits an inverse relationship with WSS. The result is a stenotic lesion. The presence of downstream venous stenosis causes an inflow-outflow mismatch resulting in increased pressure within the access. Qa in this situation may be decreased, increased, or within a normal range. Over time, the increased intraluminal pressure can result in marked aneurysmal changes within the AVF, difficulties with cannulation and the dialysis treatment, and ultimately, increasing risk of access thrombosis. Complete characterization of the lesion both hemodynamically and anatomically should be the first step in developing a strategy for management. This requires both access flow measurement and angiographic imaging. Patients with CAS present a relatively broad spectrum as relates to both of these parameters. These data should be used to determine whether primary treatment of CAS should be directed toward the anatomical lesion (small MLD and low Qa) or the pathophysiology (large MLD and high Qa).

First-in-human evaluation of a biological regenerative vascular conduit for hemodialysis access.

INTRODUCTION: The long-term survival and low complication rate of autogenous fistulas for hemodialysis access is often offset by early thrombosis and slow or failed maturation leading to the use of central venous catheters. A regenerative material may have the potential to overcome these limitations. A completely biological acellular vascular conduit was investigated in this first-in-human clinical study. METHODS: With approval of the ethics board and patients' informed consent, five subjects were enrolled based on predetermined inclusion criteria. Five patients underwent implant of a novel acellular, biological tissue conduit (TRUE AVC™) in the upper arm in a curved configuration between brachial artery and axillary vein. After maturation, standard dialysis was commenced through the new access. Patients were followed up to 26 weeks with ultrasound and physical exam. Serum samples were evaluated for an immune response to the novel allogeneic human tissue implant. RESULTS: This new tissue conduit handled well surgically, with properties similar to that of native human vein. Post procedure conduit flow was excellent in all cases, averaging 1098 ± 388 ml/min at week 4 and remaining stable through 1248 ± 355 ml/min at 26 weeks. Surgical site healing was normal with no edema or erythema by week 4. Six-month primary assisted patency was 80% and secondary patency was 100%. Prescribed dialysis was successfully delivered without infection, and there was no significant change in conduit diameter. Serum testing showed no increase in PRA or IgG specific to the TRUE AVC. One implant required intervention at 5 months with thrombectomy and covered stent procedure. CONCLUSION: This first-in-human 6-month study with favorable patency and low complication rate establishes the initial safety and feasibility of this novel biological tissue conduit for dialysis access in patients with end-stage kidney disease. Its mechanical durability and lack of immune response establishes TRUE AVC as a potential regenerative material for clinical use.

Proteinuria among patients with chronic kidney disease: a performance measure for improving patient outcomes.

BACKGROUND: In an effort to improve identification and treatment of patients with chronic kidney disease (CKD), the National Kidney Foundation (NKF) developed the Kidney Disease Quality Outcomes Initiative (KDQOI) clinical practice guidelines, which include measurement of proteinuria among all patients with CKD who are not receiving chronic dialysis therapy. Encouraging dissemination and utilization of these guidelines may be enhanced by the development of performance measures. The question of whether adequate evidence exists to advocate for the measurement of proteinuria in CKD as a performance measure was explored. METHODS: The US Preventive Services Task Force "chain of evidence" framework was used to guide evidence synthesis from the systematic review. Five questions were applied to specific links in the evidence chain: (1) Is there direct evidence that testing for proteinuria improves health outcomes? (2) What is the yield of testing, in terms of both accuracy and reliability of the test and the prevalence of undiagnosed proteinuria? (3) What adverse effects result from testing a person for proteinuria? (4) Does treatment of proteinuria as a result of testing provide an incremental benefit in health outcomes? and (5) What adverse effects result from treating a person for proteinuria? The systematic search specifically targeted meta-analyses and systematic reviews. FINDINGS: The systematic review revealed no direct evidence that testing for proteinuria among patients with CKD reduced incidence of end-stage renal disease (ESRD). However, the strong links between testing, treatment, and outcome suggest a correlation between proteinuria testing and ESRD. CONCLUSIONS: Current evidence suggests that proteinuria testing (using the albumin-to-creatinine ratio [ACR]) among patients with CKD would be an appropriate health care quality performance measure for improving patient outcomes.

Novel classification of proximal forearm perforator vein in the planning and creation of percutaneous and surgical Gracz-type arteriovenous fistulae.

BACKGROUND: The perforator vein determines whether it is feasible to create a percutaneous (pAVF) or surgical "Gracz-type" arteriovenous fistula (sAVF). Creating a standard anatomic classification of the antecubital region is beneficial to both the selection of the appropriate device and/or procedure and technical outcomes. Accordingly, an analysis of a large cohort of patients undergoing pAVF/sAVF was performed, focusing on perforator vein anatomical suitability, and a novel anatomical classification of the antecubital region was developed and proposed. METHODS: Between August 2018 and July 2022, chronic or end-stage kidney disease patients as well as patients anticipated an initiation of apheresis, who were referred for vascular access planning, underwent a standardized evaluation of upper extremities. A vessel mapping summary detailing the vasculature and the access creation plan was completed, indicating the anatomical suitability for sAVF and pAVF (Ellipsys and WavelinQ) techniques. RESULTS: Of 524 patients, 36.5% were female (average age 65 years). 53.2% were on dialysis, 41.6% had diabetes, and 13.2% had a previously failed permanent dialysis access. The anatomy for successful pAVF creation was judged to be suitable in 54% of patients for an Ellipsys-pAVF, and 29.8% for WavelinQ-pAVF. Of the WavelinQ group, 54.4% had suitable anatomy for ulnar, 26.9% for radial, and 18.6% for both ulnar/radial anastomoses. Additionally, 60.7% had suitable anatomy for pAVF creation with at least one of the systems, while 22.5% were suited for both types of pAVF-systems. 80.3% were candidates for creation of a Gracz-AVF. CONCLUSION: Overall, we found that about 60% of patients are likely candidates for a pAVF, with 80% being candidates for creation of a Gracz-AVF. Male patients have significantly higher suitability for most types of AVF creation, and younger patients are more suitable for Ellipsys-pAVF and RCAVFs. Most importantly, a universal classification of perforator vein was developed, which is indispensable in modern vascular access planning.

Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-κB signaling.

Long COVID, a type of post-acute sequelae of SARS-CoV-2 (PASC), has been associated with sustained elevated levels of immune activation and inflammation. However, the mechanisms that drive this inflammation remain unknown. Inflammation during acute coronavirus disease 2019 could be exacerbated by microbial translocation (from the gut and/or lung) to blood. Whether microbial translocation contributes to inflammation during PASC is unknown. We did not observe a significant elevation in plasma markers of bacterial translocation during PASC. However, we observed higher levels of fungal translocation - measured as ß-glucan, a fungal cell wall polysaccharide - in the plasma of individuals experiencing PASC compared with those without PASC or SARS-CoV-2-negative controls. The higher ß-glucan correlated with higher inflammation and elevated levels of host metabolites involved in activating N-methyl-d-aspartate receptors (such as metabolites within the tryptophan catabolism pathway) with established neurotoxic properties. Mechanistically, ß-glucan can directly induce inflammation by binding to myeloid cells (via Dectin-1) and activating Syk/NF-κB signaling. Using a Dectin-1/NF-κB reporter model, we found that plasma from individuals experiencing PASC induced higher NF-κB signaling compared with plasma from negative controls. This higher NF-κB signaling was abrogated by piceatannol (Syk inhibitor). These data suggest a potential targetable mechanism linking fungal translocation and inflammation during PASC.

Achieving the goal of the Fistula First breakthrough initiative for prevalent maintenance hemodialysis patients.

BACKGROUND: The Centers for Medicare & Medicaid Services (CMS) established a national goal of 66% arteriovenous fistula (AVF) use in prevalent hemodialysis (HD) patients for the current Fistula First Breakthrough Initiative. The feasibility of achieving the goal has been debated. We examined contemporary patterns of AVF use in prevalent patients to assess the potential for attaining the goal by dialysis facilities and their associated End-Stage Renal Disease Networks in the United States. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: US dialysis facilities with a mean HD patient census of 10 or more during the 40-month study period, January 2007-April 2010. OUTCOMES & MEASUREMENTS: Mean changes in facility-level AVF use and percentage of facilities achieving the 66% prevalent AVF goal within the United States and each network. RESULTS: Mean prevalent AVF use within dialysis facilities increased from 45.3% to 55.5% (P < 0.001) in the United States, but varied substantially across regions. The percentage of facilities achieving the 66% AVF use goal increased from 6.4% to 19.0% (P < 0.001). During the 40 months, 35.9% of facilities achieved the CMS goal for at least 1 month. On average, these facilities sustained mean use ≥66% for 12.9 ± 11.7 (SD) months. Case-mix and other facility characteristics explained 20% of the variation in proportion of facility patients using an AVF in the last measured month, leaving substantial unexplained variability. LIMITATIONS: This analysis is limited by the absence of facility case-mix data over time, and the national scope of the initiative precludes use of a comparison group. CONCLUSIONS: Achieving the CMS goal of 66% prevalent AVF use is feasible for individual dialysis facilities. There is a need to decrease regional variation before the CMS goal can be fully realized for US HD facilities.

Increased plasma chymase concentration and mast cell chymase expression in venous neointimal lesions of patients with CKD and ESRD.

The underlying inflammatory component of chronic kidney disease may predispose blood vessels to intimal hyperplasia (IH), which is the primary cause of dialysis access failure. We hypothesize that vascular pathology and markers of IH formation are antecedent to arteriovenous (AV) fistula creation. Blood, cephalic, and basilic vein segments were collected from predialysis chronic kidney disease (CKD) patients with no previous AV access and patients with end-stage renal disease (ESRD). Immunohistochemistry was performed with antibodies against mast cell chymase, transforming growth factor-beta (TGF-ß) and interleukin-6 (IL-6), which cause IH. Plasma chymase was measured by ELISA. IH was present in 91% of CKD and 75% of ESRD vein segments. Chymase was abundant in vessels with IH, with the greatest expression in intima and medial layers, and virtually absent in the controls. Chymase colocalized with TGF-ß1 and IL-6. Plasma chymase concentration was elevated up to 33-fold in patients with CKD versus controls and was associated with increased chymase in vessels with IH. We show that chymase expression in vessels with IH corresponds with plasma chymase concentrations. As chymase inhibition attenuates IH in animal models, and we find chymase is highly expressed in IH lesions of patients with CKD and ESRD, we speculate that chymase inhibition could have therapeutic value in humans.

25-hydroxyvitamin D concentration is inversely associated with serum MMP-9 in a cross-sectional study of African American ESRD patients.

BACKGROUND: Circulating 25-hydroxyvitamin D [25(OH)D] concentration is inversely associated with peripheral arterial disease and hypertension. Vascular remodeling may play a role in this association, however, data relating vitamin D level to specific remodeling biomarkers among ESRD patients is sparse. We tested whether 25(OH)D concentration is associated with markers of vascular remodeling and inflammation in African American ESRD patients. METHODS: We conducted a cross-sectional study among ESRD patients receiving maintenance hemodialysis within Emory University-affiliated outpatient hemodialysis units. Demographic, clinical and dialysis treatment data were collected via direct patient interview and review of patients records at the time of enrollment, and each patient gave blood samples. Associations between 25(OH)D and biomarker concentrations were estimated in univariate analyses using Pearson's correlation coefficients and in multivariate analyses using linear regression models. 25(OH) D concentration was entered in multivariate linear regression models as a continuous variable and binary variable (<15 ng/ml and ≥15 ng/ml). Adjusted estimate concentrations of biomarkers were compared between 25(OH) D groups using analysis of variance (ANOVA). Finally, results were stratified by vascular access type. RESULTS: Among 91 patients, mean (standard deviation) 25(OH)D concentration was 18.8 (9.6) ng/ml, and was low (<15 ng/ml) in 43% of patients. In univariate analyses, low 25(OH) D was associated with lower serum calcium, higher serum phosphorus, and higher LDL concentrations. 25(OH) D concentration was inversely correlated with MMP-9 concentration (r = -0.29, p = 0.004). In multivariate analyses, MMP-9 concentration remained negatively associated with 25(OH) D concentration (P = 0.03) and anti-inflammatory IL-10 concentration positively correlated with 25(OH) D concentration (P = 0.04). CONCLUSIONS: Plasma MMP-9 and circulating 25(OH) D concentrations are significantly and inversely associated among ESRD patients. This finding may suggest a potential mechanism by which low circulating 25(OH) D functions as a cardiovascular risk factor.

Geographic concentration of poverty and arteriovenous fistula use among ESRD patients.

There is substantial geographic variability in both incident and prevalent arteriovenous fistula (AVF) use among patients with ESRD. This study examined the degree to which these variations associate with poverty in the county of a patient's treatment center. We performed a cross-sectional study including 28,135 patients treated by 1127 hemodialysis centers in five ESRD networks (16 states) between June 1, 2005 and May 31, 2006. We used the 2000 U.S. Census to categorize county-level poverty and ascertained incident AVF use from the Medicare CMS 2728 form. We calculated the 30-month slope of change in AVF prevalence from monthly facility reports collected between 2003 and 2005. More than 33% of treatment centers were located in high-poverty counties. County poverty inversely associated with incident AVF use (P for trend = 0.001). In contrast, substantial increases in prevalent AVF rates from 30.9 to 38.6% (P < 0.001) among treatment centers did not associate with county poverty (P = 0.9519). In conclusion, the concentration of poverty in the county where a treatment is located associates with incident AVF use by patients with ESRD but not with subsequent improvement in AVF use among prevalent patients. These results suggest that the Medicare ESRD program may mitigate poverty effects on AVF use.

Metabolic Changes in Peripheral Blood Mononuclear Cells Isolated From Patients With End Stage Renal Disease.

As numerous complex pathologies stem from cellular energy dysfunction, we aimed to elucidate mitochondrial function and associated stress pathologies in kidney disease in a cohort of hemodialysis patients with end-stage kidney disease (ESKD). The bioenergetics study was conducted using peripheral blood mononuclear cells (PBMCs) of ESKD patients (n = 29) and healthy controls (no ESKD, n = 10). PBMCs were isolated from whole blood and seeded into assay plates to detect changes in oxidative phosphorylation and glycolysis. The bioenergetics analysis (i.e., mitochondrial stress test) was performed using Seahorse XFe24 flux analyzer. We observed significant reduction in mitochondrial respiration in patient PBMCs in terms of fundamental bioenergetics parameters such as basal respiration, ATP turnover, maximal respiration and spare respiratory capacity. These findings were correlated with the expression levels of proteins coordinating cellular energy status and regulating mitochondrial dynamics. Our data demonstrates an association between mitochondrial oxygen consumption of PBMCs and ESKD. AMPK activity, its downstream effector PGC-1α and mitochondrial fission/fusion proteins are partially responsible for the decrease in oxidative phosphorylation of PBMCs isolated from ESKD patients. We propose a link between mitochondrial dysfunction and ESKD and a role for mitochondria as a potential site for therapeutic interventions.

Reduced myocardial blood flow reserve in kidney transplant candidates may hamper risk stratification.

BACKGROUND: Vasodilator nuclear stress testing is frequently ordered for risk stratification prior to kidney transplantation. Since 82Rb-positron emission tomography-computed tomography can measure myocardial blood flow (MBF), the response to vasodilator stress can be verified rendering the results of the scan more reliable. METHODS: We reviewed the MBF response to dipyridamole infusion in 328 patients with end-stage kidney disease (ESKD) prior to transplant (188 hemodialysis-HD, 120 peritoneal dialysis-PD, and 20 pre-dialysis patients-CKD5) and in 100 controls with normal kidney function. A stress/rest MBF ratio ≥ 2 was considered an adequate response to dipyridamole. Coronary artery calcium (CAC) was measured on CT. RESULTS: Inadequate MBF response was seen in 36%-HD, 21%-PD, 45%-CKD5 vs. 23%-controls (p = 0.006). Univariable predictors of poor MBF response in ESKD patients were age, diabetes mellitus, and CAC (all p < 0.03) while serum hemoglobin was borderline significant (p = 0.052). Multivariable predictors of a poor MBF response were age (p = 0.002) and lower serum hemoglobin (p = 0.014). Ischemia was identified in 8% of ESKD patients and 24% of controls (p < 0.001). CONCLUSIONS: ESKD patients are less likely to respond appropriately to vasodilator stress compared to patients with normal renal function and had a lower incidence of ischemia despite a high pre-test probability of disease. Physicians performing vasodilator stress without MBF measurement should be aware of the high probability of a false negative response.