Effects of a More Selective Arteriovenous Fistula Strategy on Vascular Access Outcomes.

SIGNIFICANCE STATEMENT: The optimal choice of vascular access for patients undergoing hemodialysis-arteriovenous fistula (AVF) or arteriovenous graft (AVG)-remains controversial. In a pragmatic observational study of 692 patients, the authors found that among patients who initiated hemodialysis with a central vein catheter (CVC), a strategy that maximized AVF placement resulted in a higher frequency of access procedures and greater access management costs for patients who initially received an AVF than an AVG. A more selective policy that avoided AVF placement if an AVF was predicted to be at high risk of failure resulted in a lower frequency of access procedures and access costs in patients receiving an AVF versus an AVG. These findings suggest that clinicians should be more selective in placing AVFs because this approach improves vascular access outcomes. BACKGROUND: The optimal choice of initial vascular access-arteriovenous fistula (AVF) or graft (AVG)-remains controversial, particularly in patients initiating hemodialysis with a central venous catheter (CVC). METHODS: In a pragmatic observational study of patients who initiated hemodialysis with a CVC and subsequently received an AVF or AVG, we compared a less selective vascular access strategy of maximizing AVF creation (period 1; 408 patients in 2004 through 2012) with a more selective policy of avoiding AVF creation if failure was likely (period 2; 284 patients in 2013 through 2019). Prespecified end points included frequency of vascular access procedures, access management costs, and duration of catheter dependence. We also compared access outcomes in all patients with an initial AVF or AVG in the two periods. RESULTS: An initial AVG placement was significantly more common in period 2 (41%) versus period 1 (28%). Frequency of all access procedures per 100 patient-years was significantly higher in patients with an initial AVF than an AVG in period 1 and lower in period 2. Median annual access management costs were significantly higher among patients with AVF ($10,642) versus patients with AVG ($6810) in period 1 but significantly lower in period 2 ($5481 versus $8253, respectively). Years of catheter dependence per 100 patient-years was three-fold higher in patients with AVF versus patients with AVG in period 1 (23.3 versus 8.1, respectively), but only 30% higher in period 2 (20.8 versus 16.0, respectively). When all patients were aggregated, the median annual access management cost was significantly lower in period 2 ($6757) than in period 1 ($9781). CONCLUSIONS: A more selective approach to AVF placement reduces frequency of vascular access procedures and cost of access management.

Study protocol of a randomized controlled trial of fistula vs. graft arteriovenous vascular access in older adults with end-stage kidney disease on hemodialysis: the AV access trial.

BACKGROUND: Treatment of end-stage kidney disease (ESKD) with hemodialysis requires surgical creation of an arteriovenous (AV) vascular access-fistula (AVF) or graft (AVG)-to avoid (or limit) the use of a central venous catheter (CVC). AVFs have long been considered the first-line vascular access option, with AVGs as second best. Recent studies have suggested that, in older adults, AVGs may be a better strategy than AVFs. Lacking evidence from well-powered randomized clinical trials, integration of these results into clinical decision making is challenging. The main objective of the AV Access Study is to compare, between the two types of AV access, clinical outcomes that are important to patients, physicians, and policy makers. METHODS: This is a prospective, multicenter, randomized controlled trial in adults ≥ 60 years old receiving chronic hemodialysis via a CVC. Eligible participants must have co-existing cardiovascular disease, peripheral arterial disease, and/or diabetes mellitus; and vascular anatomy suitable for placement of either type of AV access. Participants are randomized, in a 1:1 ratio, to a strategy of AVG or AVF creation. An estimated 262 participants will be recruited across 7 healthcare systems, with average follow-up of 2 years. Questionnaires will be administered at baseline and semi-annually. The primary outcome is the rate of CVC-free days per 100 patient-days. The primary safety outcome is the cumulative incidence of vascular access (CVC or AV access)-related severe infections-defined as access infections that lead to hospitalization or death. Secondary outcomes include access-related healthcare costs and patients' experiences with vascular access care between the two treatment groups. DISCUSSION: In the absence of studies using robust and unbiased research methodology to address vascular access care for hemodialysis patients, clinical decisions are limited to inferences from observational studies. The goal of the AV Access Study is to generate evidence to optimize vascular access care, based on objective, age-specific criteria, while incorporating goals of care and patient preference for vascular access type in clinical decision-making. TRIAL REGISTRATION: This study is being conducted in accordance with the tenets of the Helsinki Declaration, and has been approved by the central institutional review board (IRB) of Wake Forest University Health Sciences (approval number: 00069593) and local IRB of each participating clinical center; and was registered on Nov 27, 2020, at ClinicalTrials.gov (NCT04646226).

Abnormal time-zero histology is predictive of kidney transplant outcomes.

INTRODUCTION: Time-zero biopsies can detect donor-derived lesions at the time of kidney transplantation, but their utility in predicting long-term outcomes is unclear under the updated Kidney Allocation System. METHODS: We conducted a single-center retrospective cohort study of 272 consecutive post-reperfusion time-zero biopsies. We tested the hypothesis that abnormal time-zero histology is a strong indicator of donor quality that increases the precision of the kidney donor profile index (KDPI) score to predict long-term outcomes. RESULTS: We detected abnormal biopsies in 42% of the cohort, which were independently associated with a 1.2-fold increased hazard for a composite of acute rejection, allograft failure, and death after adjusting for clinical characteristics including KDPI. By Kaplan-Meier analysis, the relationship between abnormal time-zero histology and the composite endpoint was only significant in the subgroup of deceased donor kidney transplants with KDPI scores >35. Abnormal time-zero histology, particularly vascular intimal fibrosis and arteriolar hyalinosis scores, was independently associated with lower 12-month estimated GFR. CONCLUSION: In conclusion, abnormal time-zero histology is relatively common and identifies a group of kidney recipients at increased risk for worse long-term outcomes. Further studies are needed to determine the optimal patient population in which to deploy time-zero biopsies as an additional surveillance tool.

Redefining the Influence of Ethnicity on Simultaneous Kidney and Pancreas Transplantation Outcomes: A 15-year Single-center Experience.

OBJECTIVE: To examine the largest single-center experience of simultaneous kidney/pancreas transplantation (SPK) transplantation among African-Americans (AAs). BACKGROUND: Current dogma suggests that AAs have worse survival following SPK than white recipients. We hypothesize that this national trend may not be ubiquitous. METHODS: From August 30, 1999, through October 1, 2014, 188 SPK transplants were performed at the University of Alabama at Birmingham (UAB) and 5523 were performed at other US centers. Using Kaplan-Meier survival estimates and Cox proportional hazards regression, we examined the influence of recipient ethnicity on survival. RESULTS: AAs comprised 36.2% of the UAB cohort compared with only 19.1% nationally (P < 0.01); yet, overall, 3-year graft survival was statistically higher among UAB than US cohort (kidney: 91.5% vs 87.9%, P = 0.11; pancreas: 87.4% vs 81.3%; P = 0.04, respectively) and persisted on adjusted analyses [kidney adjusted hazard ratio (aHR): 0.58, 95% confidence interval (95% CI) 0.35-0.97, P = 0.04; pancreas aHR: 0.54, 95% CI 0.34-0.85, P = 0.01]. Among the UAB cohort, graft survival did not differ between AA and white recipients; in contrast, the US cohort experienced significantly lower graft survival rates among AA than white recipients (kidney 5 years: 76.5% vs 82.3%, P < 0.01; pancreas 5 years: 72.2% vs 76.3%, P = 0.01; respectively). CONCLUSION: Among a single-center cohort of SPK transplants overrepresented by AAs, we demonstrated similar outcomes among AA and white recipients and better outcomes than the US experience. These data suggest that current dogma may be incorrect. Identifying best practices for SPK transplantation is imperative to mitigate racial disparities in outcomes observed at the national level.

Mitigating Racial and Sex Disparities in Access to Living Donor Kidney Transplantation: Impact of the Nation's Longest Single-center Kidney Chain.

OBJECTIVE: In this study, we sought to assess likelihood of living donor kidney transplantation (LDKT) within a single-center kidney transplant waitlist, by race and sex, after implementation of an incompatible program. SUMMARY BACKGROUND DATA: Disparities in access to LDKT exist among minority women and may be partially explained by antigen sensitization secondary to prior pregnancies, transplants, or blood transfusions, creating difficulty finding compatible matches. To address these and other obstacles, an incompatible LDKT program, incorporating desensitization and kidney paired donation, was created at our institution. METHODS: A retrospective cohort study was performed among our kidney transplant waitlist candidates (n = 8895). Multivariable Cox regression was utilized, comparing likelihood of LDKT before (era 1: 01/2007-01/2013) and after (era 2: 01/2013-11/2018) implementation of the incompatible program. Candidates were stratified by race [white vs minority (nonwhite)], sex, and breadth of sensitization. RESULTS: Program implementation resulted in the nation's longest single-center kidney chain, and likelihood of LDKT increased by 70% for whites [adjusted hazard ratio (aHR) 1.70; 95% confidence interval (CI), 1.46-1.99] and more than 100% for minorities (aHR 2.05; 95% CI, 1.60-2.62). Improvement in access to LDKT was greatest among sensitized minority women [calculated panel reactive antibody (cPRA) 11%-49%: aHR 4.79; 95% CI, 2.27-10.11; cPRA 50%-100%: aHR 4.09; 95% CI, 1.89-8.82]. CONCLUSIONS: Implementation of an incompatible program, and the resulting nation's longest single-center kidney chain, mitigated disparities in access to LDKT among minorities, specifically sensitized women. Extrapolation of this success on a national level may further serve these vulnerable populations.

Clinical Outcomes and Economic Impact of Starting Hemodialysis with a Catheter after Predialysis Arteriovenous Fistula Creation.

BACKGROUND: Patients with advanced chronic kidney disease frequently undergo arteriovenous fistula creation prior to reaching end-stage renal disease (ESRD), but some initiate hemodialysis with a central vein catheter, if their fistula is not yet usable. The clinical consequences of the delay in fistula use have not been quantified in such patients. We compared patients with pre-ESRD fistula surgery who initiated dialysis with a catheter versus a fistula in terms of the frequency of post-dialysis vascular access procedures and complications and their economic impact. METHODS: We identified 205 patients with predialysis fistula creation from 2006 to 2012 at a large dialysis center who started hemodialysis within the ensuing 2 years. Of these, 91 (44%) initiated dialysis with a catheter and 114 (56%) with a fistula. We compared these 2 groups in terms of their annual frequency of percutaneous vascular access procedures, surgical access procedures, total access procedures, hospitalizations due to catheter-related bacteremia, and overall cost of vascular access management. RESULTS: The 2 groups were similar in demographics, comorbidities, and fistula type. As compared to patients initiating dialysis with a fistula, those initiating with a catheter had a significantly greater annual frequency of percutaneous access procedures (1.29 [1.19-1.40] vs. 0.75 [0.68-0.82]), surgical access procedures (0.69 [0.61-0.76] vs. 0.59 [0.53-0.66]), total access procedures (1.98 [1.86-2.11] vs. 1.34 [1.26-1.44]), and hospitalizations due to catheter-related bacteremia (0.09 [0.07-0.12] vs. 0.02 [0.01-0.03]). Patients initiating dialysis with a catheter incurred a median overall annual cost of access management that was USD 2,669 higher (USD 6,372 [3,121-12,242) vs. USD 3,703 [1,867-6,953], p = 0.0001). CONCLUSION: Among patients with predialysis fistula creation, those initiating dialysis with a catheter versus a fistula had substantially more frequent percutaneous, surgical, and total vascular access procedures, as well as hospitalizations due to catheter-related bacteremia. The annual cost of access management was substantially higher in those initiating dialysis with a catheter.

Decreasing deceased donor transplant rates among children (≤6 years) under the new kidney allocation system.

The Kidney Allocation System (KAS) was implemented in December 2014 with unknown impact on the pediatric waitlist. To understand the effect of KAS on pediatric registrants, deceased donor kidney transplant (DDKT) rate was assessed using interrupted time series analysis and time-to-event analysis. Two allocation eras were defined with an intermediary washout period: Era 1 (01/01/2013-09/01/2014), Era 2 (09/01/2014-03/01/2015), and Era 3(03/01/2015-03/01/2017). When using Cox proportional hazards, there was no significant association between allocation era and DDKT likelihood as compared to Era 1 (Era 3: aHR: 1.07, 95% CI: 0.97-1.18, P = .17). However, this was not consistent across all subgroups. Specifically, while highly sensitized pediatric registrants were consistently less likely to be transplanted than their less sensitized counterparts, this disparity was attenuated in Era 3 (Era 1 aHR: 0.04, 95%CI: 0.01-0.14, P < .001; Era 3 aHR: 0.33, 95% CI: 0.21-0.53, P < .001) whereas the youngest registrants aged 0-6 experienced a 21% decrease in DDKT likelihood in Era 3 as compared to Era 1 (aHR: 0.79, 95% CI: 0.64-0.98, P = .03). Thus, while overall DDKT likelihood remained stable with the introduction of KAS, registrants ≤ 6 years of age were disadvantaged, warranting further study to ensure equitable access to transplantation.

Choice of a second vascular access in hemodialysis patients whose initial arteriovenous fistula failed to mature.

OBJECTIVE: We have previously shown that arteriovenous fistulas (AVFs) are more expensive to create and to maintain than arteriovenous grafts (AVGs) in patients undergoing their first access. Because those for whom this first access fails may be a more disadvantaged group, we hypothesized that the cost of a second access may be different from that in the primary access group. With this in mind, we compared access costs in patients receiving a secondary AVF or AVG after their initial AVF failed to mature. METHODS: This was a retrospective cohort study of 92 patients who received a second vascular access (44 AVFs and 48 AVGs) after their first AVF failed to mature. We quantified the yearly frequency of percutaneous or surgical access interventions and catheter-related bacteremias (CRBs) using a computerized vascular access database. The costs associated with access procedures were quantified using the outpatient prospective payment schedule, and those related to hospitalization for CRB were determined from the diagnosis-related groups fee schedule. RESULTS: Patients receiving an AVF had fewer percutaneous procedures than those receiving an AVG (2.09 [95% confidence interval, 1.86-2.34] vs 2.61 [2.35-2.88]; P = .004), tended to undergo surgical interventions more frequently (1.21 [1.04-1.40] vs 1.00 [0.84-1.17]; P = .08), and experienced a similar yearly frequency of CRB hospitalizations (0.40 [0.31-0.52 vs 0.28 [0.20-0.38]; P = .07). Patients with a secondary AVF vs an AVG had a similar median yearly cost of percutaneous access interventions ($3567 [interquartile range, $1219-$4680] vs $4989 [$1570-$9752]; P = .14) and surgical access procedures ($6403 [$3494-$13,127] vs $4728 [$2563-$12,254]; P = .38) but a higher annual cost for CRBs ($3405 [$0-$12,825] vs $0 [$0-$5477]; P = .04). The total yearly access-related cost was similar in both groups ($19,477 [$9162-$36,916] vs $18,285 [$6850-$31,768]; P = .56). CONCLUSIONS: Patients undergoing a secondary AVF required more surgical procedures and sustained more bacteremia complications than patients undergoing a secondary AVG implantation. There was no significant difference in the total cost of access care for hemodialysis patients receiving a secondary AVF vs AVG.

The Clinical and Economic Effect of Vascular Access Selection in Patients Initiating Hemodialysis with a Catheter.

Patients in the United States frequently initiate hemodialysis with a central venous catheter (CVC) and subsequently undergo placement of a new arteriovenous fistula (AVF) or arteriovenous graft (AVG). Little is known about the clinical and economic effects of initial vascular access choice. We identified 479 patients starting hemodialysis with a CVC at a large medical center (during 2004-2012) who subsequently had an AVF (n=295) or AVG (n=105) placed or no arteriovenous access (CVC group, n=71). Compared with patients receiving an AVG, those receiving an AVF had more frequent surgical access procedures per year (1.01 [95% confidence interval, 0.95 to 1.08] versus 0.62 [95% confidence interval, 0.55 to 0.70]; P<0.001) but a similar frequency of percutaneous access procedures per year. Patients receiving an AVF had a higher median annual cost (interquartile range) of surgical access procedures than those receiving an AVG ($4857 [$2523-$8835] versus $2819 [$1411-$4274]; P<0.001), whereas the annual cost of percutaneous access procedures was similar in both groups. The AVF group had a higher median overall annual access-related cost than the AVG group ($10,642 [$5406-$19,878] versus $6810 [$3718-$13,651]; P=0.001) after controlling for patient age, sex, race, and diabetes. The CVC group had the highest median annual overall access-related cost ($28,709 [$11,793-$66,917]; P<0.001), largely attributable to the high frequency of hospitalizations due to catheter-related bacteremia. In conclusion, among patients initiating hemodialysis with a CVC, the annual cost of access-related procedures and complications is higher in patients who initially receive an AVF versus an AVG.

Arteriovenous Fistula Development in the First 6 Weeks after Creation.

PURPOSE: To assess the anatomic development of native arteriovenous fistula (AVF) during the first 6 weeks after creation by using ultrasonographic (US) measurements in a multicenter hemodialysis fistula maturation study. MATERIALS AND METHODS: Each institutional review board approved the prospective study protocol, and written informed consent was obtained. Six hundred and two participants (180 women and 422 men, 459 with upper-arm AVF and 143 with forearm AVF) from seven clinical centers underwent preoperative artery and vein US mapping. AVF draining vein diameter and blood flow rate were assessed postoperatively after 1 day, 2 weeks, and 6 weeks. Relationships among US measurements were summarized after using multiple imputation for missing measurements. RESULTS: In 55% of forearm AVFs (68 of 124) and 83% of upper-arm AVFs (341 of 411) in surviving patients without thrombosis or AVF intervention prior to 6 weeks, at least 50% of their 6-week blood flow rate measurement was achieved at 1 day. Among surviving patients without thrombosis or AVF intervention prior to week 2, 70% with upper-arm AVFs (302 of 433) and 77% with forearm AVFs (99 of 128) maintained at least 85% of their week 2 flow rate at week 6. Mean AVF diameters of at least 0.40 cm were seen in 85% (389 of 459), 91% (419 of 459), and 87% (401 of 459) of upper-arm AVFs and in 40% (58 of 143), 73% (104 of 143), and 77% (110 of 143) of forearm AVFs at 1 day, 2 weeks, and 6 weeks, respectively. One-day and 2-week AVF flow rates and diameters were used to predict 6-week levels, with 2-week prediction of 6-week measures more accurate than those of 1 day (flow rates, R(2) = 0.47 and 0.61, respectively; diameters, R(2) = 0.49 and 0.82, respectively). CONCLUSION: AVF blood flow rate at 1 day is usually more than 50% of the 6-week blood flow rate. Two-week measurements are more predictive of 6-week diameter and blood flow than those of 1 day. US measurements at 2 weeks may be of value in the early identification of fistulas that are unlikely to develop optimally.

Outcomes of arteriovenous fistulas and grafts with or without intervention before successful use.

OBJECTIVE: Arteriovenous fistulas (AVFs) are considered superior to arteriovenous grafts (AVGs) because of longer secondary patency after successful cannulation for dialysis. We evaluated whether access interventions before successful cannulation affect the relative longevity of AVFs and AVGs after successful use. METHODS: This retrospective study of a prospective database identified patients who initiated dialysis with a catheter and subsequently had a permanent access (289 AVFs and 310 AVGs) placed between January 1, 2006, and December 31, 2011, and were successfully cannulated for dialysis at a large medical center. Patients were monitored until June 30, 2014, and we evaluated the clinical outcomes (secondary patency and frequency of interventions) of the vascular accesses. RESULTS: An intervention before successful cannulation was required more frequently with AVFs than with AVGs (50.5% vs 17.7%; odds ratio, 4.74; 95% confidence interval [CI], 3.26-6.86; P < .0001). Compared with AVFs that matured without interventions, those that required intervention had shorter secondary patency after successful cannulation (hazard ratio, 1.84; 95% CI, 1.30-2.60; P < .0001) and required more interventions per year after successful use (rate ratio [RR], 1.81; 95% CI, 1.49-2.20; P < .0001). Similarly, AVGs that required intervention before successful cannulation had shorter secondary patency than those without prior intervention (odds ratio, 1.98; 95% CI, 1.52-4.02; P < .0001) and required more interventions per year after successful use (RR, 1.49; 95% CI, 1.27-1.74; P < .0001). AVFs requiring intervention before maturation had inferior secondary patency compared with AVGs that were cannulated without prior intervention (hazard ratio, 1.45; 95% CI, 1.08-2.01; P = .01), but required fewer annual interventions after successful use (RR, 0.57; 95% CI, 0.49-0.66; P < .0001). CONCLUSIONS: The patency advantage of AVFs over AVGs is no longer evident in patients requiring an AVF intervention before successful cannulation, but the AVFs require fewer interventions after successful use.

Preoperative arterial microcalcification and clinical outcomes of arteriovenous fistulas for hemodialysis.

BACKGROUND: Arteriovenous fistulas (AVFs) often fail to mature, but the mechanism of AVF nonmaturation is poorly understood. Arterial microcalcification is common in patients with chronic kidney disease (CKD) and may limit vascular dilatation, thereby contributing to early postoperative juxta-anastomotic AVF stenosis and impaired AVF maturation. This study evaluated whether preexisting arterial microcalcification adversely affects AVF outcomes. STUDY DESIGN: Prospective study. SETTING & PARTICIPANTS: 127 patients with CKD undergoing AVF surgery at a large academic medical center. PREDICTORS: Preexisting arterial microcalcification (≥1% of media area) assessed independently by von Kossa stains of arterial specimens obtained during AVF surgery and by preoperative ultrasound. OUTCOMES: Juxta-anastomotic AVF stenosis (ascertained by ultrasound obtained 4-6 weeks postoperatively), AVF nonmaturation (inability to cannulate with 2 needles with dialysis blood flow ≥ 300mL/min for ≥6 sessions in 1 month within 6 months of AVF creation), and duration of primary unassisted AVF survival after successful use (time to first intervention). RESULTS: Arterial microcalcification was present by histologic evaluation in 40% of patients undergoing AVF surgery. The frequency of a postoperative juxta-anastomotic AVF stenosis was similar in patients with or without preexisting arterial microcalcification (32% vs 42%; OR, 0.65; 95% CI, 0.28-1.52; P=0.3). AVF nonmaturation was observed in 29%, 33%, 33%, and 33% of patients with <1%, 1% to 4.9%, 5% to 9.9%, and ≥10% arterial microcalcification, respectively (P=0.9). Sonographic arterial microcalcification was found in 39% of patients and was associated with histologic calcification (P=0.001), but did not predict AVF nonmaturation. Finally, among AVFs that matured, unassisted AVF maturation (time to first intervention) was similar for patients with and without preexisting arterial microcalcification (HR, 0.64; 95% CI, 0.35-1.21; P=0.2). LIMITATIONS: Single-center study. CONCLUSIONS: Arterial microcalcification is common in patients with advanced CKD, but does not explain postoperative AVF stenosis, AVF nonmaturation, or AVF failure after successful cannulation.

Risk Evaluation of Immediate Surgical Failure During Thigh Hemodialysis Graft Placement by Sonographic Screening.

OBJECTIVES: The purpose of this study was to determine whether preoperative sonographic evaluation of vascular diameters and calcification identifies patients at risk for immediate technical failure of thigh hemodialysis grafts. METHODS: A retrospective analysis of 143 chronic hemodialysis patients who underwent thigh graft placement was performed. All patients underwent preoperative sonography to assess arterial and venous waveforms and vascular diameters. The degree of arterial calcification was assessed retrospectively. Patient characteristics and graft outcomes were examined. Statistical analyses were performed, with P< .05 considered clinically significant. RESULTS: Sonography identified no or mild arterial calcification in 113 of 143 patients (79%) and moderate to severe calcification in 30 of 143 patients (21%). Primary surgical technical failure occurred in 23% of patients (7 of 30) with moderate to severe calcification, compared to 3.5% (4 of 113) of those with no or mild calcification (hazard ratio, 6.59; 95% confidence interval, 2.06-21.05; P = .002). Cumulative graft survival (time to permanent failure) was shorter in patients with moderate to severe arterial calcification (3-year graft survival, 37% versus 56%; hazard ratio, 2.32; 95% confidence interval, 1.48-6.69; P= .003) but was not significantly associated with venous (P= .82) or arterial (P = .43) diameters. CONCLUSIONS: Preoperative sonographic assessment of thigh vessel diameters and calcification can identify patients who may be at risk for immediate technical graft failure and decreased cumulative graft survival. The use of sonography as a screening examination may improve preoperative assessment and surgical planning of hemodialysis thigh grafts.

Correlation of pre-existing vascular pathology with arteriovenous graft outcomes in hemodialysis patients.

BACKGROUND: Arteriovenous grafts (AVGs) are prone to neointimal hyperplasia leading to AVG failure. We hypothesized that pre-existing pathologic abnormalities of the vessels used to create AVGs (including venous intimal hyperplasia, arterial intimal hyperplasia, arterial medial fibrosis, and arterial calcification) are associated with inferior AVG survival. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: Patients with chronic kidney disease undergoing placement of a new AVG at a large medical center who had vascular specimens obtained at the time of surgery (n = 76). PREDICTOR: Maximal intimal thickness of the arterial and venous intima, arterial medial fibrosis, and arterial medial calcification. OUTCOME & MEASUREMENTS: Unassisted primary AVG survival (time to first intervention) and frequency of AVG interventions. RESULTS: 55 patients (72%) underwent interventions and 148 graft interventions occurred during 89.9 years of follow-up (1.65 interventions per graft-year). Unassisted primary AVG survival was not associated significantly with arterial intimal thickness (HR, 0.72; 95% CI, 0.40-1.27; P = 0.3), venous intimal thickness (HR, 0.64; 95% CI, 0.37-1.10; P = 0.1), severe arterial medial fibrosis (HR, 0.58; 95% CI, 0.32-1.06; P = 0.6), or severe arterial calcification (HR, 0.68; 95% CI, 0.37-1.31; P = 0.3). The frequency of AVG interventions per year was associated inversely with arterial intimal thickness (relative risk [RR], 1.99; 95% CI, 1.16-3.42; P < 0.001 for thickness <10 vs. >25 µm), venous intimal thickness (RR, 2.11; 95% CI, 1.39-3.20; P < 0.001 for thickness <5 vs. >10 µm), arterial medial fibrosis (RR, 3.17; 95% CI, 1.96-5.13; P < 0.001 for fibrosis <70% vs. ≥70%), and arterial calcification (RR, 2.12; 95% CI, 1.31-3.43; P = 0.001 for <10% vs. ≥10% calcification). LIMITATIONS: Single-center study. Study may be underpowered to demonstrate differences in unassisted primary AVG survival. CONCLUSIONS: Pre-existing vascular pathologic abnormalities in patients with chronic kidney disease may not be associated significantly with unassisted primary AVG survival. However, vascular intimal hyperplasia, arterial medial fibrosis, and arterial calcification may be associated with a decreased frequency of AVG interventions.

Vascular Access-Related Distal Ischemia Requiring Intervention: Frequency, Risk Factors, and Consequences.

BACKGROUND: Distal ischemia is a rare complication in patients undergoing placement of an arteriovenous (AV) fistula or AV graft. There are limited studies on its frequency, risk factors, clinical consequences, or feasibility of subsequent access. METHODS: A prospective vascular access database from a large academic medical center was queried retrospectively to identify 1498 patients (mean age 56±15 years, 48% female patients, 73% Black patients) undergoing placement of at least one vascular access from 2011 to 2020. For patients who developed access-related distal ischemia requiring surgical intervention, we determined the frequency of distal ischemia, clinical risk factors, and subsequent outcomes. RESULTS: Severe access-related distal ischemia occurred in 28 patients (1.9%; 95% confidence interval, 1.3% to 2.7%). The frequency was 0.2% for forearm AV fistulas, 0.9% for upper arm AV fistulas, 2.4% for forearm AV grafts, 2.2% for upper arm AV grafts, and 2.8% for thigh AV grafts. Risk factors independently associated with distal ischemia included female sex (odds ratio [OR], 3.64 [95% confidence interval, 1.52 to 8.72]), peripheral vascular disease (OR, 6.28 [2.84 to 13.87]), and coronary artery disease (OR, 2.37 [1.08 to 5.23]). Surgical interventions included ligation, excision, plication (banding), and other surgical procedures. Five patients developed tissue necrosis. A subsequent AV graft was placed in 13 patients, of whom only one (8%) developed distal ischemia requiring intervention. CONCLUSIONS: Access-related distal ischemia requiring intervention was rare in this study and more common in women and patients with peripheral vascular disease or coronary artery disease. In some cases, a subsequent vascular access could be placed with a low likelihood of recurrent distal ischemia.

Predialysis Vascular Access Placement and Catheter Use at Hemodialysis Initiation.

BACKGROUND: Current guidelines encourage placement of an arteriovenous (AV) fistula in patients with advanced CKD to avoid initiation of hemodialysis with a central venous catheter. However, the relative merits of predialysis placement of an AV fistula or graft have been poorly studied. METHODS: This study included 380 patients (mean age 59±14 years, 73% Black patients, 51% male) from a large academic medical center who underwent predialysis placement of an AV fistula (286) or AV graft (94). The study quantified three end points: time from access placement to initiation of dialysis, likelihood of starting hemodialysis without a catheter, and number of vascular access procedures before dialysis initiation. RESULTS: The eGFR at access surgery was <10, 10-14, and ≥15 ml/min per 1.73 m 2 in 87 (23%), 179 (47%), and 114 (30%) patients, respectively. The median time from access surgery to hemodialysis initiation was 69, 156, and 429 days in patients with an eGFR of <10, 10-14, and ≥15 ml/min per 1.73 m 2 , respectively ( P < 0.001). Hemodialysis was initiated within 2 years of access surgery in 298 (78%) of the patients. Catheter-free hemodialysis initiation was higher in patients with an AV graft versus an AV fistula when the eGFR was <10 ml/min per 1.73 m 2 (88% versus 43%; odds ratio [OR], 9.10 [95% confidence interval, 2.74 to 26.4]) and when the eGFR was 10-14 ml/min per 1.73 m 2 (88% versus 54%; OR, 6.05 [2.35 to 15.0]) but similar when the eGFR was ≥15 ml/min per 1.73 m 2 (90% versus 75%; OR, 3.00 [0.48 to 34.9]). Patients undergoing an AV fistula were more likely to undergo an angioplasty (11% versus 0%, P < 0.001), surgical access revision (26% versus 8%, P < 0.001), a second access placement (16% versus 6%, P = 0.02), and a catheter insertion (32% versus 11%, P < 0.001). CONCLUSIONS: Among patients with CKD undergoing vascular access surgery when their eGFR was <15 ml/min per 1.73 m 2 , catheter use at dialysis initiation was much less likely when an AV graft, rather than an AV fistula, was placed.

Medial fibrosis, vascular calcification, intimal hyperplasia, and arteriovenous fistula maturation.

BACKGROUND: Arteriovenous fistulas (AVFs) for hemodialysis frequently fail to mature because of inadequate dilation or early stenosis. The pathogenesis of AVF nonmaturation may be related to pre-existing vascular pathologic states: medial fibrosis or microcalcification may limit arterial dilation, and intimal hyperplasia may cause stenosis. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: Patients with chronic kidney disease (N = 50) undergoing AVF placement. PREDICTORS: Medial fibrosis, microcalcification, and intimal hyperplasia in arteries and veins obtained during AVF creation. OUTCOME & MEASUREMENTS: AVF nonmaturation. RESULTS: AVF nonmaturation occurred in 38% of patients despite attempted salvage procedures. Preoperative arterial diameter was associated with upper-arm AVF maturation (P = 0.007). Medial fibrosis was similar in patients with nonmaturing and mature AVFs (60% ± 14% vs 66% ± 13%; P = 0.2). AVF nonmaturation was not associated with patient age or diabetes, although both variables were associated significantly with severe medial fibrosis. Conversely, AVF nonmaturation was higher in women than men despite similar medial fibrosis in both sexes. Arterial microcalcification (assessed semiquantitatively) tended to be associated with AVF nonmaturation (1.3 ± 0.8 vs 0.9 ± 0.8; P = 0.08). None of the arteries or veins obtained at AVF creation had intimal hyperplasia. However, repeated venous samples obtained in 6 patients during surgical revision of an immature AVF showed venous neointimal hyperplasia. LIMITATIONS: Single-center study. CONCLUSION: Medial fibrosis and microcalcification are frequent in arteries used to create AVFs, but do not explain AVF nonmaturation. Unlike previous studies, intimal hyperplasia was not present at baseline, but developed de novo in nonmaturing AVFs.

Eplet mismatch scores and de novo donor-specific antibody development in simultaneous pancreas-kidney transplantation.

Antibody-mediated rejection is the principal cause of allotransplant graft failure. Available studies differ on the impact of de novo donor specific antibody (dnDSA) in pancreas transplants but are limited by patient sample size and sera sample collection. High-resolution HLA incompatibility scoring algorithms are able to more accurately predict dnDSA development. We hypothesized that HLA incompatibility scores as determined by the HLA-Matchmaker, HLA-EMMA, and PIRCHE-II algorithms would serve as a predictor of de novo donor specific antibody (dnDSA) development and clarify the role dnDSA as detrimental to simultaneous pancreas-kidney graft survival. Our results show that female sex and race were significantly associated with dnDSA development and dnDSA development resulted in worse kidney and pancreas graft survival. The majority of individuals who developed dnDSA (88%), developed anti-HLA-DQ antibody in some combination with anti-HLA class I or -DR. A multivariate analysis of the incompatibility scores showed that both HLA-Matchmaker and PIRCHE-II scores predicted anti-DQ dnDSA development. An optimal cutoff threshold for incompatibility matching was obtained for these scores and demonstrated statistical significance when predicting freedom from anti-DQ DSA development. In conclusion, increased scores from high-resolution HLA matching predict dnDSA development, and dnDSA is associated with antibody-mediated rejection and worse pancreas and kidney graft outcomes.

Systolic dysfunction portends increased mortality among those waiting for renal transplant.

Individuals waiting for a renal transplant experience excessive cardiovascular mortality, which is not fully explained by the prevalence of ischemic heart disease in this population. Overt heart failure is known to increase the mortality of patients with ESRD, but the impact of lesser degrees of ventricular systolic dysfunction is unknown. For examination of the association between left ventricular ejection fraction(LVEF) and mortality of renal transplant candidates, the records of 2718 patients evaluated for transplantation at one institution were reviewed. During 6355 patient-years (median 27 mo) of follow-up, 681 deaths occurred. Patients with systolic dysfunction (LVEF

Are there still roles for exocrine bladder drainage and portal venous drainage for pancreatic allografts?

PURPOSE OF REVIEW: Controversy remains regarding the best methodology of handling exocrine pancreatic fluid and pancreatic venous effluent. Bladder drainage has given way to enteric drainage. However, is there an instance in which bladder drainage is preferable? Also, hyperinsulinemia, as a result of systemic venous drainage (SVD), is claimed to be proatherosclerotic, whereas portal venous drainage (PVD) is more physiologic and less atherosclerotic. RECENT FINDINGS: Bladder drainage remains a viable method of exocrine pancreas drainage, but evidence is sparse that measuring urinary amylase has a substantial benefit in the early detection of acute rejection in all types of pancreas transplants. Currently, there is no incontrovertible evidence that systemic hyperinsulinemia is proatherosclerotic, whereas recent metabolic studies on SVD and PVD showed that there was no benefit to PVD. SUMMARY: Given the advent of newer immunosuppressive agents and overall lower acute rejection rates, the perceived benefit of bladder drainage as a means to measure urinary amylase as an early marker of rejection has not been substantiated. However, there may be a selective role for bladder drainage in 'high risk' pancreases. Also, without a clear-cut metabolic benefit to PVD over SVD, it remains the surgeon's choice as to which method to use.