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

Toxins (Basel). 2019 May 13;11(5):268. 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.

Keywords: CCN intercellular signalling proteins; Connective tissue growth factor; cardiovascular disease; convection; end stage kidney disease; haemodiafiltration; haemodialysis; mortality.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / mortality*
  • Cardiovascular Diseases / physiopathology
  • Cause of Death
  • Connective Tissue Growth Factor / blood*
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Kidney Diseases / blood
  • Kidney Diseases / mortality*
  • Kidney Diseases / physiopathology
  • Male
  • Middle Aged
  • Renal Dialysis*

Substances

  • CCN2 protein, human
  • Connective Tissue Growth Factor