Coagulation, thrombophilia and patency of arteriovenous fistula in children undergoing haemodialysis compared with healthy volunteers: a prospective analysis.

UNLABELLED: This study aimed to assess whether markers of coagulation, fibrinolysis or thrombophilia are increased in children on haemodialysis compared with controls and whether measurement of any of these factors could help to identify patients at an increased risk of arteriovenous fistula (AVF) occlusion. Blood samples were taken from 55 children immediately before a session of haemodialysis and from 20 healthy volunteers. Thrombin-antithrombin (TAT), D-dimer, plasmin-antiplasmin (PAP) and anticardiolipin immunoglobulin G (ACA-Ig G) were measured by ELISA. Factor V Leiden mutation (G1691A) was determined by gene polymorphism [restriction fragment length polymorphism (RFLP)]. Determination of the patency of the AVF was prospectively followed up for a minimum of 4 years or until the AVF was nonfunctioning. Fifty-five patients were studied with a median follow-up of 659 days (range 30-1670 days). A significant increase was found in the levels of D-dimer, PAP and ACA-Ig G in haemodialysis patients with thrombosed and nonthrombosed native AVFs vs. CONTROLS: There was a significant difference between both chronic haemodialysis patients with thrombosed and nonthrombosed native AVF with regard to ACA-IgG levels. At 1 year follow-up, primary patency was 61.4% (27 patients). In multivariate analysis, D-dimer was inversely associated with secondary patency.Thrombophilia may predispose children with end stage renal disease to access failure. The promising finding is that in children on haemodialysis, D-dimer levels were increased and inversely correlated with secondary patency. Further evaluation is required into the possible role of D-dimer as a biomarker of AVF occlusion.

Endothelial nitric oxide synthase gene intron4 VNTR polymorphism in patients with chronic kidney disease.

Nitric oxide production is reduced in renal disease, partially due to decreased endothelial nitric oxide production. Evidence indicates that nitric oxide deficiency contributes to cardiovascular events and progression of kidney damage. A polymorphism in intron 4 of the endothelial constitutive nitric oxide synthase (ecNOS) gene is a candidate gene in cardiovascular and renal diseases. We investigated a potential involvement of this polymorphism in chronic renal failure. A case-control study involved 78 children with chronic kidney disease (CKD) and 30 healthy controls. All participants were genotyped for the ecNOS4 polymorphism by the polymerase chain reaction (PCR). Dialyzed (maintenance hemodialysis) and conservative treatment children had significantly higher frequency of the aa genotype and ecNOS4a allele (P<0.05) compared with controls. The combined genotype aa+ab vs. bb comparison validated that a allele is a high-risk allele for end-stage renal disease (ESRD) (P<0.05). Serum nitric oxide level was found to be lower in carriers of the ecNOS 4a allele than in noncarriers (100.29±27.32 vs. 152.73±60.39 µmol/l, P=0.04). Interestingly, 85.95% of the ecNOS 4a allele ESRD patients were found hypertensive in comparison to the 60.67% patients of non noncarriers (bb genotype) (P=0.04). Also, 35.90% of the ecNOS 4a allele ESRD patients were found to have cardiovascular disease in comparison to the 5.13% patients of noncarriers (bb genotype) (P=0.01). On multiple linear regression analysis, a allele was independently associated with hypertension (P=0.03). There was a significantly higher frequency of the ecNOS4a allele carriers among CKD children, both on MHD and conservative treatment than in controls. This suggests that the ecNOS gene polymorphism may be associated with an increased risk of chronic renal failure.