This was a retrospective case-control study of patients who received maintenance hemodialysis (MHD) and underwent AVF creation. All patients had end stage renal disease (ESRD) and were treated with MHD at the CHA Bundang Medical Center hemodialysis center between 2006 and 2015. We selected patients who received percutaneous intervention or surgery to revise their fistula after successful use of AVF for at least three months to be enrolled in the late AVF failure group. In the percutaneous intervention, vessels were dilated using a balloon catheter [Armada™ 35 (Abbott Vascular, Santa Clara, CA, USA), MUSTANG™ (Boston Scientific Co., Marlborough, MA, USA)] with a diameter varying from 4–8 mm. The balloon was inflated for 30–60 seconds and repeated as necessary. Balloon inflation pressure was 14–24 atm as recommended by the manufacturer.

Vascular access failure events occurred in 195 patients during that time period. Among those patients, 68 had an AVG. Only 51 patients were ultimately included in the late AVF failure group (Fig. 1). Fifty-one controls were selected from our centers whose AVF had been patent without an episode of access failure for at least 24 months. Neither cases nor controls had a history of cancer, coagulation disorder, active infection, or AVG with synthetic material. AVF operations were performed within one month after the first MHD in both groups. All patients initiated AVF cannulation within 3 months after AVF formation. All patients were undergoing chronic bicarbonate hemodialysis for a mean time of 4.0 hours, three times a week. The blood flow rate ranged between 250 and 300 mL/min, whereas a dialysate flow rate of 500 mL/min was routinely used. Kt/V was evaluated monthly as a marker of dialysis efficiency. The study was approved by the Institutional Review Board of the CHA Bundang Medical Center, CHA Uni-versity. Because the study involved the analysis of data already collected and the data had individual identifying information removed, the ethics board waived the need for individual patient consent.

Patient demographic, clinical, and vascular access data, including age, gender, and etiology of ESRD (e.g., diabetes, hypertension, glomerulonephritis, polycystic kidney disease, or unknown), AVF site (forearm or upper arm), medications (antihypertensive drugs, antiplatelet agents, calcium containing agents, or vitamin D analogues), heparin dose, and other comorbidities (ischemic heart disease, cerebrovascular disease, or peripheral vascular disease), were obtained by medical record review. Cardiovascular diseases were defined when patients had any medical history of angina pectoris, positive treadmill test, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass surgery, or congestive heart failure. Cerebrovascular diseases were defined when patients had any medical history of stroke, transient ischemic attack, or intracranial hemorrhage. The combined cardiovascular disease group included patients who had cardiovascular and cerebrovascular disease. Laboratory findings were collected, including serum hemoglobin, serum calcium, blood urea nitrogen, phosphate, intact parathyroid hormone (iPTH), uric acid, total cholesterol, low density lipid cholesterol, c-reactive protein (CRP), 25-hydroxyvitamin D, and albumin, at the time of the first access cannulation. The mean weekly erythropoietin doses and the mean hemoglobin level were calculated using medical records through the period from the first AVF use to an event or at least two years after the first AVF cannulation for the control group. For dose conversion, 1 mcg of darbepoetin alpha was converted to 200 IU epoetin alpha.11 Blood flow rate data were collected for the three most recent hemodialysis treatments for controls or for the last three hemodialysis treatments before late AVF failure for cases. Loss of AVF patency due to thrombosis was defined as the need for percutaneous intervention, thrombectomy, or reconstruction surgery to revise the fistula.

Categorical variables were recorded as numbers and percentages. Continuous variables were presented as the mean±standard deviation. Student's t-test and the Mann-Whitney U test were used to compare continuous variables. Categorical variables were compared using the χ² test or Fisher's exact test. Binary logistic regression analysis was performed to investigate the effects of covariates on AVF patency. All p-values<0.050 were considered significant. Statistical analyses were performed using SPSS for Windows (version 21; SPSS Inc., Chicago, IL, USA).

Clinical and biochemical characteristics are shown in Table 1. The mean age of the study population was 54.2±13.5 years, and men comprised 61.7% of the population. The etiologies of ESRD were diabetic nephropathy (62.7%), hypertension (21.5%), glomerulonephritis (5.8%), autosomal dominant polycystic kidney disease (1.9%), and unknown (7.8%). Most patients had radiocephalic fistulas in the forearm (88.2%). The mean initial dose of heparin was 1039.2±376.8 IU/mL, and the maintenance dose was 300.9±179.6 IU/mL/hr. The mean ESA dose was 5972.0±2828.6 IU/mL/wk and 99.4±50.0 IU/mL/wk/kg (Table 1).

The mean duration of MHD was 59.7±32.2 months in the control group and 11.8±4.2 months in the late AVF failure group. The mean time from the first cannulation to late loss of AVF patency was 8.4±4.2 months.

Among the 51 eligible late AVF failure patients, most AVF stenoses were located in the proximal draining vein. The stenotic sites in 23 patients were in the proximal draining veins, and the sites in 20 patients were near both anastomosis sites and the proximal draining veins. Of these patients, one opted to abandon the original access site and underwent double lumen catheter insertion, and two underwent a thrombectomy. The remaining 48 patients underwent percutaneous angioplasty, of which all were successful.

Baseline demographics and comorbidities of patients who developed late loss of functional AVF patency were compared with patients without AVF failure in Table 1. Patients with late AVF failure were significantly older and more likely to have comorbid conditions, such as hypertension, diabetes mellitus, and cardiovascular disease. Additionally, patients with late AVF failure had significantly lower serum albumin and iPTH levels, compared to patients without late AVF failure. Blood flow rates during MHD treatment were significantly lower in the group with late AVF failure. Most importantly, the average weekly dose of ESA was significantly higher in the patients with late loss of functional AVF patency (4782.2±2360.5 IU/mL/wk vs. 7161.8±2775.2 IU/mL/wk, p<0.001 and 79.2±42.4 IU/mL/wk/kg vs. 119.6±49.2 IU/mL/wk/kg, p<0.001) (Table 1, Fig. 2). Serum hemoglobin levels, however, were not different between groups. We also compared mean hemoglobin levels between groups during the period from the first AVF use to an event or at least two years since the first AVF cannulation for the control group. The mean hemoglobin level was slightly higher in the AVF failure group, although the difference was not statistically significant (9.6±0.5 g/dL vs. 9.5±1.5 g/dL, p=0.728) (Fig. 3).

No differences in sex, access location, or medications were observed between those with and without late failure (Table 1 and 2).

Binary logistic regression analysis was performed to assess the effects of covariates on AVF patency (Table 3). We used the continuous value of ESA in IU/mL/wk/kg to evaluate the effect of ESA dose. The variables chosen for inclusion in the multivariable logistic regression analysis were those found to be significantly correlated with late loss of functional patency on univariate analysis. Variables that met this criterion were age; presence of diabetes, hypertension, or ischemic heart disease; blood flow rate; serum albumin; iPTH; and dose of ESA. The only independent predictor of late loss of AVF patency in multivariate analysis was a high average ESA dose (odds ratio=1.015, 95% confidence interval=1.002–1.028, p=0.022) (Table 3).