Jeffrey J. Sands

Facility Hemodialysis Vascular Access Use and Mortality in Countries Participating in DOPPS: An Instrumental Variable Analysis

BACKGROUND Previously, the Dialysis Outcomes and Practice Patterns Study (DOPPS) has shown large international variations in vascular access practice. Greater mortality risks have been seen for hemodialysis (HD) patients dialyzing with a catheter or graft versus a native arteriovenous fistula (AVF). To further understand the relationship between vascular access practice and outcomes, we have applied practice-based analyses (using an instrumental variable approach) to decrease the treatment-by-indication bias of prior patient-level analyses. STUDY DESIGN A prospective observational study of HD practices. SETTING & PARTICIPANTS Data collected from 1996 to 2004 from 28,196 HD patients from more than 300 dialysis units participating in the DOPPS in 12 countries. PREDICTOR OR FACTOR Patient-level or case-mix-adjusted facility-level vascular access use. OUTCOMES/MEASUREMENTS: Mortality and hospitalization risks. RESULTS After adjusting for demographics, comorbid conditions, and laboratory values, greater mortality risk was seen for patients using a catheter (relative risk, 1.32; 95% confidence interval, 1.22 to 1.42; P < 0.001) or graft (relative risk, 1.15; 95% confidence interval, 1.06 to 1.25; P < 0.001) versus an AVF. Every 20% greater case-mix-adjusted catheter use within a facility was associated with 20% greater mortality risk (versus facility AVF use, P < 0.001); and every 20% greater facility graft use was associated with 9% greater mortality risk (P < 0.001). Greater facility catheter and graft use were both associated with greater all-cause and infection-related hospitalization. Catheter and graft use were greater in the United States than in Japan and many European countries. More than half the 36% to 43% greater case-mix-adjusted mortality risk for HD patients in the United States versus the 5 European countries from the DOPPS I and II was attributable to differences in vascular access practice, even after adjusting for other HD practices. Vascular access practice differences accounted for nearly 30% of the greater US mortality compared with Japan. LIMITATIONS Possible existence of unmeasured facility- and patient-level confounders that could impact the relationship of vascular access use with outcomes. CONCLUSIONS Facility-based analyses diminish treatment-by-indication bias and suggest that less catheter and graft use improves patient survival.

The effect of Doppler flow screening studies and elective revisions on dialysis access failure.

A retrospective study was undertaken to see if screening ultrasounds and elective surgical revision could decrease access failure. Two hundred fifty-three accesses [177 gortex grafts, 76 arteriovenous (AV) fistulas] were studied with duplex imaging. Patients were subdivided by access type, flow, percent stenosis, and whether they were surgically revised. Data was examined to determine access failure within 6 months. Ten of 76 fistulas clotted (13.1%), while 53 of 177 grafts clotted (29.9%) (p = 0.005). In Gortex grafts, stenosis (p < 0.05) and decreased flow (p = 0.005) correlated with clotting. In unrevised grafts with flow < or = 801 ml/min, 13 of 14 (92.8%) clotted, whereas of those with flow > or = 1603 ml/min only, 10 of 38 (26.3%) clotted (chi-square = 24.74; p < 0.0001). Only 1 of 18 (5.6%) revised grafts with flow < or = 1300 ml/min clotted, while 29 of 69 (42%) unrevised grafts clotted (p = 0.004). We were unable to demonstrate decreased clotting in fistulae with revisions. In conclusion, screening duplex scanning was able to select groups with a higher risk of access failure over the subsequent 6 months. Elective revision with correction of areas of stenosis in grafts with flows < or = 1300 ml/min significantly decreased the incidence of clotting.

Intradialytic hypotension: frequency, sources of variation and correlation with clinical outcome.

Intradialytic hypotension (IH) is a frequent complication of hemodialysis (HD) and is associated with increased patient mortality and cardiovascular events. We studied IH to determine its variability, correlates, and clinical impact in 13 outpatient HD facilities. Blood pressure was captured by machine download. IH was defined as >30 mmHg decrease in systolic blood pressure to <90 mmHg. Risk factors were assessed by logistic regression and hospitalization by Poisson regression. Time to death and first hospitalization were assessed using Kaplan–Meier analysis in patients completing >20 HD treatments. We studied IH in 44,801 treatments (Tx) in 1137 patients. IH was frequent (17.2% of treatments) and highly variable by patient (0–100% Tx) and dialysis facility (11.1–25.8% Tx). 25.1% of patients had no IH (0% Tx) and 16.2% had IH on >35% Tx. Increased IH frequency was associated with age, female gender, diabetes, Hispanic origin, longer end stage renal disease vintage, higher body mass index, higher ultrafiltration volume, the second and third weekly Tx, lower pre‐HD systolic blood pressure, higher difference between prescribed and achieved post‐HD weight, and higher dialysate temperature. Dialysis facility was an independent predictor of IH frequency. Patients with >35% IH treatments had poorer survival (P = 0.036), and more frequent and longer hospitalization (P = 0.04, P = 0.002, respectively) than patients without IH. In conclusion, IH frequency was highly variable, associated with individual facilities, patient and treatment characteristics, and correlated with mortality and hospitalization. Identifying practice patterns associated with IH coupled with routine reporting of IH will facilitate medical management and may result in the prevention of IH, decreased mortality, and decreased hospitalization.

Pharmacomechanical thrombolysis with urokinase for treatment of thrombosed hemodialysis access grafts. A comparison with surgical thrombectomy.

Seventy-one consecutively occluded polytetrafluoroethylene (PTFE) grafts treated with pharmacomechanical thrombolysis were compared with 75 surgical controls. The patients undergoing thrombomechanical lysis had a comparable rate of successful declotting (91% vs. 90.7%) and no significant difference in patency at 24 and 48 hr, 1 week, and 1 and 6 months. Patients undergoing thrombolysis required less overnight hospitalization (17 vs. 82%) (P < 0.001) and their hospital stays averaged 1.03 days versus 3.43 days in the surgical thrombectomy group (P < 0.0001). Complication rates were similar in both groups. Hospital charges and physician fees were significantly lower in the thrombolysis group, with total charges averaging

Antibodies to topical bovine thrombin correlate with access thrombosis

6,802 versus

Vascular access monitoring improves outcomes.

12,740 (P = 0.0018). These cost differences were maintained even when patients with extended stays were excluded. In conclusion, pharmacomechanical thrombolysis provides efficacy and complications comparable to surgical thrombectomy, with the benefits of a decreased rate of hospitalization, decreased total number of days of hospitalization, and significant cost savings. The authors determined that pharmacomechanical thrombolysis is the preferable first intervention for acutely occluded PTFE grafts.

Effects of Citrate Acid Concentrate (Citrasate ) on Heparin N Requirements and Hemodialysis Adequacy: A Multicenter, Prospective Noninferiority Trial

Bovine thrombin is often used topically to promote hemostasis during vascular surgery, including dialysis-access placement. Patients frequently develop antibodies to bovine thrombin preparations, and some may develop antiphospholipid antibodies. We evaluated 88 hemodialysis patients for the presence of antibodies to topical bovine thrombin to determine if elevated antibody levels correlated with vascular access thrombosis. Twenty-seven patients (30.7%) had elevated antibody levels to topical bovine thrombin. More patients with elevated antibody levels had prior vascular access thrombosis than patients with normal antibody levels (13 of 27 versus 5 of 61 patients; P < 0.001). This difference was almost entirely the result of greater levels of thrombosis in patients with polytetrafluoroethylene (PTFE) grafts and elevated antibody levels. In these patients, 11 of 13 patients (84.6%) with elevated antibody levels had a previous thrombosis compared with 2 of 15 patients (13. 3%) with normal antibody levels (P < 0.001). Patients with elevated antibody levels and PTFE grafts also had more prior thromboses (1.92 +/- 1.60 versus 0.133 +/- 0.35 thromboses; P < 0.01) and a greater thrombosis rate (66.89 +/- 63.71 versus 4.65 +/- 12.05 thromboses/100 patient-years; P < 0.01) than patients with normal antibody levels. There were no differences in the frequency of myocardial infarction, coronary artery bypass, access age, presence of diabetes mellitus, platelet counts, anticardiolipin antibody, albumin, lactate dehydrogenase, or C-reactive protein levels. In conclusion, patients with PTFE grafts and elevated antibody levels to topical bovine thrombin had significantly more vascular access thrombosis.

Hemodialysis Access Flow Measurement—Comparison of Ultrasound Dilution and Duplex Ultrasonography

Vascular access monitoring can identify patients at increased risk of future access thrombosis. When coupled with a program of elective stenosis correction, access thrombosis rates decline approximately 50–75%. This results in arteriovenous (AV) fistula thrombosis rates of 0.1–0.2/patient year (vs. 0.2–0.4 at baseline) and AV graft thrombosis rates <0.5/patient year (vs. 0.8–1.2 thromboses/patient year at baseline). Evaluating the long-term impact on access survival remains problematic. There are no large-scale randomized trials and existing studies exhibit marked differences in target populations, clinical protocols and outcome definitions. Differences in payment systems also significantly influence the efficacy of monitoring and intervention programs. Despite these challenges, the current data support the K/DOQI recommendations that all patients undergo a program of regular access monitoring preferably by access flow measurement coupled with prompt imaging and elective stenosis correction for low flow accesses.

Difference Between Delivered and Prescribed Blood Flow in Hemodialysis

Background: Citrasate®, citric acid dialysate (CD), contains 2.4 mEq of citric acid (citrate), instead of acetic acid (acetate) as in standard bicarbonate dialysate. Previous studies suggest CD may improve dialysis adequacy and decrease heparin requirements, presumably due to nonsystemic anticoagulant effects in the dialyzer. Methods: We prospectively evaluated 277 hemodialysis patients in eight outpatient facilities to determine if CD with reduced heparin N (HN) would maintain dialyzer clearance. Subjects progressed through four study periods [baseline (B): bicarbonate dialysate + 100% HN; period 1 (P1): CD + 100% HN; period 2 (P2): CD + 80% HN; period 3 (P3): CD + 66.7% HN]. The predefined primary endpoint was noninferiority (margin –8%) of the percent change in mean dialyzer conductivity clearance between baseline and P2. Results: Subjects were 57.4% male, 41.7% white, 54.3% black, and 44.4% diabetic; mean age was 59 ± 14.4 years; mean time on dialysis was 1,498 ± 1,165 days; 65.7% had arteriovenous fistula, 19.9% arteriovenous graft, 14.4% catheters, and 27.8% used antiplatelet agents. Mean dialyzer clearance increased 0.9% (P1), 1.0% (P2), and 0.9% (P3) with CD despite heparin reduction. SpKt/V remained stable (B: 1.54 ± 0.29; P1: 1.54 ± 0.28; P2: 1.55 ± 0.27; P3: 1.54 ± 0.26). There was no significant difference in dialyzer/dialysis line thrombosis, post-HD time to hemostasis, percent of subjects with adverse events (AEs), or study-related AEs. Conclusions: CD was safe, effective, and met all study endpoints. Dialyzer clearance increased approximately 1% with CD despite 20–33% heparin reduction. Over 92% of P3 subjects demonstrated noninferiority of dialyzer clearance with CD and 33% HN reduction. There was no significant difference in dialyzer clotting, bleeding, or adverse events.

Where Are All the AV Fistulas

Decreased hemodialysis access flow is associated with an increased risk of access thrombosis. Duplex ultrasonography can measure access flow and select a subset of patients at increased risk for access failure. With in-line techniques (ultrasound dilution), access flow can be measured during hemodialysis. This study attempted to determine if access flow measured by ultrasound dilution (QA-T) was comparable to that measured by duplex ultrasonography (QA-S). The authors performed 66 simultaneous measurements of hemodialysis access flow in 19 patients by ultrasound dilution and duplex ultrasound with time-domain correlation during 19 hemodialysis treatments. The mean access flow was 1,086 +/- 505 ml/min by ultrasound dilution and 1,026 +/- 513 ml/min with duplex ultrasonography (NS). Regression analysis revealed a linear relationship between the two techniques described by the equation QAT = 246.14 + 0.8104(QAS) (correlation coefficient of 0.83; p < 0.0001). Measurement of hemodialysis access flow by ultrasound dilution was essentially equivalent to that obtained by duplex ultrasound. Additional studies are needed to determine if regular in-line flow measurements can predict and prevent future access thrombosis and decreased the cost of access management.