Regulation of vascular remodeling by immune microenvironment after the establishment of autologous arteriovenous fistula in ESRD patients.

Autogenous arteriovenous fistula (AVF) is the preferred dialysis access for receiving hemodialysis treatment in end-stage renal disease patients. After AVF is established, vascular remodeling occurs in order to adapt to hemodynamic changes. Uremia toxins, surgical injury, blood flow changes and other factors can induce inflammatory response, immune microenvironment changes, and play an important role in the maintenance of AVF vascular remodeling. This process involves the infiltration of pro-inflammatory and anti-inflammatory immune cells and the secretion of cytokines. Pro-inflammatory and anti-inflammatory immune cells include neutrophil (NEUT), dendritic cell (DC), T lymphocyte, macrophage (Mφ), etc. This article reviews the latest research progress and focuses on the role of immune microenvironment changes in vascular remodeling of AVF, in order to provide a new theoretical basis for the prevention and treatment of AVF failure.

Hemodialysis duration, human platelet antigen HPA-3 and IgA isotype of anti-ß2glycoprotein I antibodies are associated with native arteriovenous fistula failure in Tunisian hemodialysis patients.

INTRODUCTION: Arteriovenous fistula (AVF) failure is a major cause of morbidity and mortality in hemodialysis patients. We assessed the role of a large panel of acquired and inherited thrombophilic markers in cases of AVF thrombosis among 101 Tunisians on chronic hemodialysis, all with native AVF. MATERIALS AND METHODS: In this case-control study, we considered the levels of fibrinogen, factor II, factor VII, factor VIII, factor IX, factor X, factor XI, factor XII, von Willebrand factor, natural coagulation inhibitors, D-Dimer, homocysteine, IgG, IgM and IgA anticardiolipin and anti-ß2glycoprotein I (anti-ß2GPI), and anti-H/PF4 antibodies; the presence of Lupus Anticoagulant; and genetic markers (Factor V Leiden, prothrombin 20210G>A, MTHFR 677C>T and 1298A>C). RESULTS: Multivariate analysis indicated that dialysis for >69 months (OR=10.12; 95% CI, 2.53 to 40.52; p=0.001), HPA-3aa genotype (OR=3.58; 95% CI, 1.36 to 9.4; p=0.01) and anti-ß2GPI IgA isotype (OR=3.4; 95% CI, 1.21 to 9.55; p=0.02) were independent risk factors for AVF thrombosis in Tunisian hemodialysis patients. Kaplan-Meier analysis showed that AVF survival was significantly lower for patients with anti-ß2GPI IgA than for patients without this isotype (log-rank test, p=0.014). CONCLUSIONS: IgA anti-ß2GPI may be of clinical relevance among Tunisians. Further studies on the polymorphism of ß2GPI and HPA systems would be helpful for identifying patient groups at high risk of AVF failure.

TNF-alpha inhibition attenuates adverse myocardial remodeling in a rat model of volume overload.

Tumor necrosis factor (TNF)-alpha is a proinflammatory cytokine that has been implicated in the pathogenesis of heart failure. In contrast, we have recently shown that myocardial levels of TNF-alpha are acutely elevated in the aortocaval (AV) fistula model of heart failure. Based on these observations, we hypothesized that progression of adverse myocardial remodeling secondary to volume overload would be prevented by inhibition of TNF-alpha with etanercept. Furthermore, a principal objective of this study was to elucidate the effect of TNF-alpha inhibition during different phases of the myocardial remodeling process. Eight-week-old male Sprague-Dawley rats were randomly divided into the following three groups: sham-operated controls, untreated AV fistulas, and etanercept-treated AV fistulas. Each group was further subdivided to study three different time points consisting of 3 days, 3 wk, and 8 wk postfistula. Etanercept was administered subcutaneously at 1 mg/kg body wt. Etanercept prevented collagen degradation at 3 days and significantly attenuated the decrease in collagen at 8 wk postfistula. Although TNF-alpha antagonism did not prevent the initial ventricular dilatation at 3 wk postfistula, etanercept was effective at significantly attenuating the subsequent ventricular hypertrophy, dilatation, and increased compliance at 8 wk postfistula. These positive adaptations achieved with etanercept administration translated into significant functional improvements. At a cellular level, etanercept also markedly attenuated increases in cardiomyocyte length, width, and area at 8 wk postfistula. These observations demonstrate that TNF-alpha has a pivotal role in adverse myocardial remodeling and that treatment with etanercept can attenuate the progression to heart failure.

Prevalence of heparin-induced antibodies in patients with chronic renal failure undergoing hemodialysis.

Heparin-induced thrombocytopenia (HIT) type II is a serious complication of heparin therapy. It presents initially as thrombocytopenia, and is associated with thrombosis in 20-50% of the cases. HIT is related to the presence of heparin-induced antibodies (HIA), which show specificity for the PF4-heparin (PF4-H) complex. The FcgammaRIIa receptor has been suggested to participate in the pathogenic mechanism of HIA. Since patients undergoing chronic hemodialysis (HD) are exposed repeatedly to heparin, we studied the prevalence of HIA and their eventual relationship with thrombocytopenia and/or thrombosis, and the possible participation of the FcgammaRIIa polymorphism. We studied 207 patients with chronic renal failure (CRF) undergoing HD. As a control we included 130 blood donors and 28 patients with CRF without HD. The HIA patients were studied with the use of a PF4-H ELISA. Additionally, in some positive cases for the previous test, a 14C- serotonin release assay (14C-SRA) was performed. The polymorphism FcgammaRIIa H/R131 was studied by polymerase chain reaction (PCR) with allele-specific primers. Thirty-seven patients (17.9%) undergoing HD presented with HIA. The majority of these antibodies were IgG, IgM, and IgA. The HIA investigated presented specificity against the PF4-H complex, but not against PF4 alone (P<0.001). Twelve out of 22 (54.5%) PF4-H antibodies were positive when tested with the 14C-SRA. The distribution of the FcgammaRIIa polymorphism in patients and healthy controls was 42.6% and 41.6% for H/H131, 41% and 48.9% for the H/R131 isoform, and 16.4% and 9.5% for the R/R131 isoform, respectively. No statistically significant difference in the FcgammaRIIa isoform distribution was found. Twenty-nine out of 156 patients (18.5%) presented thrombocytopenia, and 21/207 (12.4%) had thrombosis of the native vein arterio-venous fistula (AVF). We did not find any statistically significant between HIA and thrombocytopenia or thrombosis. An important proportion of patients with CRF undergoing HD developed HIA, but these cases were not associated with thrombocytopenia or thrombosis of AVF. The frequency of the FcgammaRIIa polymorphism did not statistically differ between HIT type II and normal controls.

Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis with intrarenal aneurysms and renal arteriovenous fistulaes.

A 78-year-old Japanese man was admitted with a complaint of slight fever and weight loss. At admission, he tested positive for myeloperoxidase (MPO)-ANCA and had renal failure. An abdominal angiography revealed atrophy of the right kidney, two or more arteriovenous fistulae (AVF) in the right renal interlobular arteries, and multiple aneurysms in both kidneys. A renal biopsy specimen showed diffuse crescentic glomerulonephritis accompanied by tubulo-interstitial changes. This case suggests the possibility of some relationship between ANCA-associated vasculitides and the formation of aneurysms and AVFs.