Investigations Pre-existing Arterial Micro-Calcification Predicts Primary Unassisted Arteriovenous Fistula Failure in Incident Hemodialysis Patients Su Jin Choi,* Hye Eun Yoon,* Young Soo Kim,* Sun Ae Yoon,* Chul Woo Yang,* Yong-Soo Kim,* Sun Cheol Park,† and Young Ok Kim* *Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea, and † Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea

ABSTRACT Vascular access micro-calcification is a risk factor for cardiovascular morbidity and mortality in hemodialysis (HD) patients but its influence on vascular access patency is still undetermined. Our study aimed to determine the impact of arterial micro-calcification (AMiC) on the patency of vascular access in HD patients. One-hundred fourteen HD patients receiving arteriovenous fistula (AVF) operation were included in this study. During the operation, we obtained partial arterial specimen and performed pathological examination by von Kossa stain to identify AMiC. We compared primary unassisted AVF failure within 1 year between positive and negative AMiC

groups, and performed Cox regression analysis for evaluating risk factor of AVF failure. The incidence of AMiC was 37.7% and AVF failure occurred in 45 patients (39.5%). The AVF failure rate within 1 year was greater in the positive AMiC group than those in the negative AMiC group (53.5% vs. 31.0%, p = 0.02). Kaplan–Meier analysis showed that the positive AMiC group had a lower AVF patency rate than the negative AMiC group (p = 0.02). The presence of AMiC was an independent risk factor for AVF failure. In conclusion, preexisting AMiC of the vascular access is associated with primary unassisted AVF failure in incident HD patients.

A native arteriovenous fistula (AVF) is regarded as the best type of vascular access for patients undergoing hemodialysis (HD) because it has fewer complications and higher long-term patency compared with arteriovenous graft (AVG). An AVF has the disadvantage however, of a longer maturation time and higher primary failure rate compared with an AVG. The main factors affecting primary AVF failure are age, gender, the presence of diabetes mellitus (DM), and the diameter of the artery and vein at the surgical site (1–3). Since the introduction of the fistula first policy, vascular mapping prior to surgery has limited the blood vessel diameter used during surgery, thereby increasing the surgical frequency of AVF (4,5). Despite this, AVF failure remains a frequent occurrence. This observation led us to suspect that pathological abnormalities, such as atherosclerosis, may also

affect AVF failure. Pathological abnormalities can be easily detected in tissue samples obtained from the artery during AVF surgery. We have conducted arterial tissue biopsies during AVF surgery and found that intimal hyperplasia and intima-media thickness were related to early AVF failure (6,7). Arterial micro-calcification (AMiC) is one of the early pathological findings of atherosclerosis, easily diagnosed using von Kossa staining, and is typically located in the media of the radial and brachial arteries obtained from the AVF surgical site. We previously reported that AMiC of the AVF surgical site occurred frequently (40–50%) in incident HD patients, and was related to cardiovascular morbidity and mortality (8,9). AMiC is thought to affect early failure of AVF since it is associated with arterial stiffness, but only a few reports have been published to date. We therefore started this study with the hypothesis that preexisting AMiC of the surgical site was highly related to AVF failure in incident HD patients who received AVF surgery.

Address correspondence to: Young Ok Kim, MD, Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701, Korea, Tel.: +8231-820-3347, Fax: +82-31-847-2719, or e-mail: [email protected]. Conflicts of interest: None to declare. Seminars in Dialysis—Vol 28, No 6 (November–December) 2015 pp. 665–669 DOI: 10.1111/sdi.12365 © 2015 Wiley Periodicals, Inc.

Subjects and Methods Patients This study was approved by the Institutional Review Board of Uijeongbu St. Mary’s Hospital, 665

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Uijeongbu city, Korea, and was a retrospective single center study that included 149 HD patients who underwent arterial biopsy during the AVF creation between March 2001 and March 2010. Of the 149 patients, 30 patients were excluded based on the exclusion criteria (nonthrombotic events such as infection and external compression, AVF failure within 1 week of surgery, because it was deemed a surgical complication, and AVG placement). And five patients were lost to follow-up or died within 3 months of AVF surgery, such that AVF outcome could not be confirmed. Finally, 114 patients were included in this study. AVF Creation and Pathologic Evaluation of AMiC Doppler ultrasonography was not routinely performed before the operation and the surgeon decided access type, such as AVF or AVG, and access location based on physical examination. Doppler ultrasonography or venography was performed in cases of poor vein development, history of ipsilateral central vein catheterization, and arm edema. Arterial specimens were obtained during AVF creation according to the method previously described (7). Briefly, 5–10 mm longitudinal elliptical excisions were taken from the incision sites of the radial or brachial artery and each specimen was fixed with formalin and embedded in paraffin. Specimens were cut into 5-lm sections and stained with hematoxylin and eosin (H&E) and von Kossa. Specimens were evaluated by a professional pathologist blinded to the clinical data. AMiC was defined as the presence of calcium deposits that appeared brown or black on von Kossa staining. Patients were divided into two groups: positive AMiC group and negative AMiC group. We compared AVF failure rate, clinical, and laboratory tests between the two groups. Follow-up of AVF Patency Arteriovenous fistula patency was followed up by physical examination, static pressure, and venography for 1 year postoperatively. Primary unassisted AVF patency was calculated from AVF creation to the first intervention (angioplasty, thrombectomy, or surgical revision) to restore blood flow or occurrence to thrombosis (10). The censored events were death, kidney transplantation, transfer to peritoneal dialysis, loss to follow-up. AVF failure was defined as requiring endovascular intervention or surgical revision to maintain patency within 1 year of the vascular access creation. Evaluation of Demographic Data and Laboratory Tests Demographic data including age, gender, comorbid diseases (DM, hypertension, coronary arterial disease, cerebrovascular disease, peripheral arterial

disease), and the site of the AVF were collected before the operation. We evaluated laboratory tests including hemoglobin, albumin, calcium, phosphorus, intact parathyroid hormone (iPTH), total cholesterol, low-density lipoprotein cholesterol, and C-reactive protein levels. Glycosylated hemoglobin (HbA1C) levels were obtained from patients with DM. Statistical Analyses Categorical variables were analyzed using numbers and percentages. Continuous variables were described as mean  SD. Comparisons of categorical variables between the two groups were performed by the Chi-square test. An independent t-test was used to compare continuous variables. The risk factors of AMiC on vascular access were evaluated by logistic regression analysis. Kaplan– Meier survival curve and log-rank test were used to compare the vascular access patency rate between the positive AMiC and negative AMiC groups. A pvalue of

Pre-existing Arterial Micro-Calcification Predicts Primary Unassisted Arteriovenous Fistula Failure in Incident Hemodialysis Patients.

Vascular access micro-calcification is a risk factor for cardiovascular morbidity and mortality in hemodialysis (HD) patients but its influence on vas...
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