Intimal CD31-Positive Relative Surfaces Are Associated with Systemic Inflammatory Markers and Maturation of Arteriovenous Fistula in Dialysis Patients

Abstract

Background: Arteriovenous fistula dysfunction is a widely disputed subject in the scientific literature on end-stage kidney disease (ESKD). The main cause of mortality and morbidity in these patients is the non-maturation or dysfunction of the arteriovenous fistula. Despite the many complications, the native arteriovenous fistula remains the gold standard in the treatment of these patients requiring renal replacement. This study aims to discuss the predictive role of some systemic inflammatory biomarkers (NLR, PLR, SII, IL-6), intimal hyperplasia, and neoangiogenesis (characterized by intimal-media CD31-positive relative surface) in arteriovenous fistula maturation failure. Methods: The present study was designed as an observational, analytical, and prospective study which included patients diagnosed with ESKD with indications of radio-cephalic arteriovenous fistula (RCAVF). Demographic data, comorbidities, preoperative laboratory data and histological/digital morphometry analysis results were processed. The patients included were divided into two groups based on their AVF maturation status at 8 weeks: “Maturation” (Group 1) and “Failed Maturation” (Group 2). Results: There was no difference in the demographic data. In terms of comorbidities, the second group had a greater incidence of heart failure (p = 0.03), diabetes (p = 0.04), peripheral artery disease (p = 0.002), and obesity (p = 0.01). Additionally, regarding the laboratory findings, these patients had higher levels of serum uric acid (p = 0.0005), phosphates (p < 0.0001), and creatinine (p = 0.02), as well as lower levels of total calcium (p = 0.0002), monocytes (p = 0.008), and lymphocytes (p < 0.0001). Moreover, all inflammatory markers (p = 0.001; p < 0.0001; p = 0.006, and p = 0.03) and Ca-P product (p < 0.0001) had higher baseline values in Group 2. Upon immunohistochemical analysis, regarding the density of neoformed vessels, there was a higher incidence of CD31-positive surfaces (p = 0.006) and CD31-positive relative surfaces (p = 0.001); the NLR (r = 0.323; p = 0.03), PLR (r = 0.381; p = 0.04), SII (r = 0.376; p = 0.03), and IL-6 (r = 0.611; p < 0.001) are all significantly correlated with vascular density, as evidenced by CD31. Conclusions: Heart failure, peripheral artery disease, obesity, and diabetes, as well as the systemic inflammatory markers (NLR, PLR, SII, IL-6), intimal hyperplasia, and CD31-positive relative surfaces are predictors of arteriovenous fistula maturation failures.

Elevated Leukocyte Glucose Index Is Associated with Long-Term Arteriovenous Fistula Failure in Dialysis Patients

“…Similarly, in our study, although we observed a lower prevalence of male patients among those who experienced AVF failure, there was no difference between male and female patients. These findings corroborate other recently published articles by Kaller et al [8,9] and Mures , an et al [10], where the authors observed no gender-related differences in AVF maturation rate [8,9] and mortality among ESKD patients [10].…”

“…Several studies have shown that inflammatory biomarkers based on blood cell counts of neutrophils, monocytes, platelets, and lymphocytes can predict AVF dysfunction [8][9][10] and long-term mortality in dialysis patients [10,16,17]. When the venous wall is exposed to arterial pressure, it undergoes a histological remodeling process that results in the proliferation, differentiation, and migration of smooth muscle cells (SMC), generating long-term intimal hyperplasia (IH) [38,39].…”

“…There are several factors that affect the maturation process and the permeability of the AVF, including the initiation of dialysis through a central venous catheter for dialysis as indicated in the results of Ravani et al [7]. Additionally, the systemic inflammatory status, as described in articles published by Kaller et al [8,9] and the preoperative diameter of the venous component are also contributing factors [8]. Moreover, patients with ESKD have several risk factors that increase the probability of primary AVF failure and death [8,[10][11][12].…”

Therapeutic strategies based on non-ionizing radiation to prevent venous neointimal hyperplasia: the relevance for stenosed arteriovenous fistula, and the role of vascular compliance

“…Due to the low pressure in the venous system, immediately after performing AVF and exposing the venous wall to arterial pressure, the remodeling process is initiated through wall distension, endothelial injury, local ischemia, and cell apoptosis ( 37 – 39 ). Overtime, these will lead to generation of inflammatory process at the venous wall and NIH ( 38 , 40 ). New methods, such as external stenting, have been developed and proposed to reduce NIH and local inflammation ( 41 ).…”

Differential expression of serum TM, PAF, and CD62P in patients with autologous arteriovenous fistula and the correlation with vascular access function

“… 5 In addition, studies have shown that inflammation at vascular access is also one of the main causes of arterial intimal hyperplasia and early thrombosis of local vessels. 6 It has been suggested that the initiating factors of intimal hyperplasia are vascular wall injury, immune/inflammatory response, and hemodynamic factors. 7 Recent studies 8 have shown that the intimal hyperplasia at the stenosis of the vascular access is obvious.…”