Imbalance of coagulation and fibrinolysis can predict vascular access failure in patients on hemodialysis after vascular access intervention.

OBJECTIVE: For patients with end-stage renal disease on hemodialysis, the durability of vascular access (VA) is still far from optimal, and access survival after intervention for access failure is an important aspect. Procoagulant status is a leading cause of access failure. Coagulation-fibrinolysis imbalance can occur in hemodialyzed patients, but the influence of the imbalance has not been fully elucidated. METHODS: We prospectively examined coagulation-fibrinolysis balance to assess the risk of access failure after the intervention of revascularization in a cohort of 462 hemodialysis patients. Thrombin-antithrombin complex (TAT) and plasmin-α2-plasmin inhibitor complex (PIC) are markers for coagulation and fibrinolysis. Median follow-up was 243 days. The end point was clinical access failure: revascularization or access revision. The survival curve for VA patency was assessed using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards regression models that allowed adjustment for baseline differences in age, sex, dialysis vintage, diabetes mellitus, and various factors (quantity of blood flow, prothrombin time-international normalized ratio, fibrin degradation products, C-reactive protein, interleukin-6, tumor necrosis factor-α, and pentraxin-3) were used. RESULTS: The 162 patients who reached an end point had smaller access flow volume and smaller percentage of arteriovenous fistula and higher TAT/PIC ratio. Kaplan-Meier analysis indicated that the patients with elevated TAT/PIC ratio showed poorer outcome (P < .001). On Cox regression modeling, elevated TAT/PIC was an independent risk factor for access failure (hazard ratio, 1.58; P = .03). CONCLUSIONS: Our results suggest that coagulation-fibrinolysis imbalance is a significant risk factor for access failure and may predict VA failure in hemodialyzed patients after access intervention.

High levels of tumor necrosis factor-α downregulate antimicrobial iron transport protein, Nramp1, in chronic hemodialysis patients: a key factor for infection risk.

BACKGROUND/AIMS: The susceptibility of patients on maintenance hemodialysis (MHD) to infections is a major cause of mortality and morbidity. Natural resistance-associated macrophage protein 1 (Nramp1) regulates intracellular pathogen proliferation, and its mRNA expression is highest in polymorphonuclear leukocytes (PMNLs). The purpose of this study was to determine the level of Nramp1 in PMNLs from MHD patients and the factors affecting its expression. METHODS: Twenty MHD patients and 24 healthy volunteers (controls) were recruited. Relative quantitative PCR was used to measure Nramp1 mRNA, and protein levels were semiquantified by means of real-time PCR and Western blot analysis or immunohistochemistry. The effect of tumor necrosis factor-α (TNF-α) or interleukin-6 (IL-6) on Nramp1 expression in PMNLs from controls was also examined. RESULTS: Nramp1 mRNA and protein levels were substantially lower in PMNLs from MHD than control subjects. Serum TNF-α levels were significantly higher in the MHD group and were inversely correlated with Nramp1 mRNA levels. The addition of TNF-α to PMNLs from control subjects decreased mRNA and protein levels of Nramp1. IL-6 did not alter Nramp1 mRNA or protein expression. CONCLUSION: We found that Nramp1 was downregulated in the PMNLs of MHD patients, which constitute the first defense barrier against bacterial challenges. High levels of TNF-α may be associated with the downregulation of Nramp1. Our findings indicate that the susceptibility to infection observed in MHD patients could be partly due to the impairment of the intracellular handling of iron and the donation of more iron to the bacteria.