Connective Tissue Growth Factor Is Related to All-cause Mortality in Hemodialysis Patients and Is Lowered by On-line Hemodiafiltration: Results from the Convective Transport Study.

Claire H Den Hoedt,Maaike K Van Gelder,Robbert Jan Kok,Marinus A Van Den Dorpel,Roel Goldschmeding,Michiel L Bots,Muriel P Grooteman,Karin G F Gerritsen,Peter J Blankestijn,Menso J Nubé

doi:10.3390/toxins11050268

Abstract

Connective tissue growth factor (CTGF) plays a key role in the pathogenesis of tissue fibrosis. The aminoterminal fragment of CTGF is a middle molecule that accumulates in chronic kidney disease. The aims of this study are to explore determinants of plasma CTGF in hemodialysis (HD) patients, investigate whether CTGF relates to all-cause mortality in HD patients, and investigate whether online-hemodiafiltration (HDF) lowers CTGF. Data from 404 patients participating in the CONvective TRAnsport STudy (CONTRAST) were analyzed. Patients were randomized to low-flux HD or HDF. Pre-dialysis CTGF was measured by sandwich ELISA at baseline, after six and 12 months. CTGF was inversely related in multivariable analysis to glomerular filtration rate (GFR) (p < 0.001) and positively to cardiovascular disease (CVD) (p = 0.006), dialysis vintage (p < 0.001), interleukin-6 (p < 0.001), beta-2-microglobulin (p = 0.045), polycystic kidney disease (p < 0.001), tubulointerstitial nephritis (p = 0.002), and renal vascular disease (p = 0.041). Patients in the highest quartile had a higher mortality risk compared to those in the lowest quartile (HR 1.7, 95% CI: 1.02–2.88, p = 0.043). HDF lowered CTGF with 4.8% between baseline and six months, whereas during HD, CTGF increased with 4.9% (p < 0.001). In conclusion, in HD patients, CTGF is related to GFR, CVD and underlying renal disease and increased the risk of all-cause mortality. HDF reduces CTGF.

Highlights

Connective tissue growth factor (CTGF/CCN2, Molecular weight (Mw) 38 kilo Dalton) is a profibrotic growth factor that plays a key role in the pathogenesis of tissue fibrosis [1]
We show that plasma CTGF is independently related to RKF, previous
cardiovascular disease (CVD), IL-6 and B2M in maintenance HD patients, which are all important predictors of mortality in this population [20,21,22,23]

Summary

Introduction

Connective tissue growth factor (CTGF/CCN2, Molecular weight (Mw) 38 kilo Dalton (kDa)) is a profibrotic growth factor that plays a key role in the pathogenesis of tissue fibrosis [1]. Plasma (N-)CTGF is exclusively eliminated by the kidneys, accumulates in chronic kidney disease, with highest levels in end stage kidney disease (ESKD) [6,7]. CTGF has been reported to be involved in various chronic diseases including systemic sclerosis, lung fibrosis, cardiac fibrosis, atherosclerosis, liver fibrosis, kidney fibrosis, diabetic nephropathy (DN), and peritoneal fibrosis in peritoneal dialysis patients [1,2]. CTGF is highly expressed in atherosclerotic plaques and has been implicated in atherogenesis [14,15,16]. In a study among 1227 patients with atherosclerotic disease, plasma CTGF was independently related to an increased risk of cardiovascular events and mortality [17]

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