Circulating Fibroblast Growth Factor-23 Level and Paraoxonase-1 Lactonase Activity in Chronic Hemodialysis Patients: Their Impact on the Incidence of Native AV Fistula Thrombosis

Abstract

Purpose: Thrombosis of native arteriovenous (AV) fistula is an important cause of complications in hemodialysis (HD) patients. The purpose of this study was to investigate the usefulness of measuring circulating fibroblast growth factor-23 (FGF-23) level and paraoxonase-1 (PON1) lactonase activity as potential predictors of native AV fistula thrombosis in chronic HD patients.Methods: This study included 83 HD patients (48 with thrombosed and 35 with non-thrombosed native AV fistulas) and 38 healthy volunteers. Serum FGF-23 level was measured using the ELISA technique, while serum PON1 lactonase activity was measured spectrophotometrically using gamma-thiobutyrolactone as a substrate.Results: FGF-23 was significantly increased while PON1 lactonase was markedly decreased in both thrombosed and non-thrombosed HD patients compared with controls (P < 0.001). FGF-23 was elevated whereas PON1 lactonase was decreased in HD patients with thrombosed native AV fistulas compared with HD patients with non-thrombosed native AV fistulas (P = 0.001 and 0.002, respectively). A significant negative correlation was found between FGF-23 and PON1 lactonase in HD patients with thrombosed native AV fistulas (r = −0.342, P = 0.017).Conclusions: This study shows a potential value of FGF-23 and PON1 lactonase as predictors of native AV fistula thrombosis in HD patients.

The importance of paraoxonase 1 activity in chronic kidney disease

“…The results demonstrated that PON1 lactonase activity was significantly decreased, whereas FGF-23 was significantly elevated in HD patients with thrombosed AV fistula compared with those with non-thrombosed AV fistula. The significant negative correlation between PON1 lactonase and FGF-23, which represents a central regulator of vascular dysfunction in CKD [ 98 ], may support the suggestion that FGF-23 and PON1 lactonase values may contribute to the prediction of native AV fistula thrombosis in HD patients [ 97 ]. In a longitudinal study with CKD patients followed- up for 3 years, it was shown that the PON1 Q192R gene variant is implicated in left ventricular (LV) hypertrophy and in LV dysfunction [ 59 ], which are surrogate indicators of CVD.…”

“…The possible associations of PON1 lactonase activity and circulating fibroblast growth factor 23 (FGF-23) levels with the incidence of native arteriovenous (AV) fistula thrombosis were examined in chronic HD patients, as AV thrombosis accounts for a great percentage of vascular access loss, developing in venous segment of native AV fistula or AV graft [ 97 ]. The results demonstrated that PON1 lactonase activity was significantly decreased, whereas FGF-23 was significantly elevated in HD patients with thrombosed AV fistula compared with those with non-thrombosed AV fistula.…”