Increased serum levels of GDF-15 associated with mortality and subclinical atherosclerosis in patients on maintenance hemodialysis

Abstract

The relationship between serum GDF-15, mortality, and carotid artery thickening suggests that GDF-15 may be a novel marker of atherosclerosis, inflammation, and malnutrition in HD patients.

Association of Growth Differentiation Factor 15 with Mortality in a Prospective Hemodialysis Cohort

“…In non-ESRD populations, an incrementally higher prevalence of elevated GDF15 levels has been observed across the cardiovascular continuum, including those patients with stable coronary artery disease, congestive heart failure, and terminal heart failure [10]. Our data add to the growing body of literature showing that, similar to cardiovascular and cancer patients, the hemodialysis population displays higher GDF15 concentrations [28]. While a consistent association between higher GDF15 levels and kidney dysfunction has been observed [10], further studies are needed to establish the sources of GDF15 production in hemodialysis patients.…”

“…To date, there have been 2 studies that have examined the relationship between GDF15 levels and mortality in end-stage renal disease patients [27,28]. In one study of 381 prevalent US hemodialysis patients by Breit et al [27], incrementally higher GDF15 levels (i.e., every 10 ng/mL increase) were independently associated with higher mortality risk.…”

“…In the Swedish subcohort, higher GDF15 levels were also associated with worse self-reported nutrition as ascertained by Subjective Global Assessment questionnaires, as well as with lower BMIs (<25). In a subsequent study of 87 hemodialysis patients from Turkey without preexisting cardiovascular disease by Yilmaz et al [28], higher GDF15 levels (i.e., every 10 ng/mL increase) were independently associated with higher mortality risk as well as subclinical atherosclerosis as assessed by carotid intima media thickness.…”

“…While limited data suggest that circulating GDF15 levels are higher in kidney dysfunction [20], there have been few studies that have examined the prognostic significance of this marker in hemodialysis patients [27,28]. Thus, to better inform the field, we sought to examine the association between GDF15 levels and mortality risk in a large, racially/ethnically diverse cohort of hemodialysis patients from the prospective, multicenter Malnutrition, Diet, and Racial Disparities in Chronic Kidney Disease (MADRAD) study who underwent rigorous, protocolized measurements of clinical and laboratory characteristics.…”

Expanded Haemodialysis Therapy of Chronic Haemodialysis Patients Prevents Calcification and Apoptosis of Vascular Smooth Muscle Cells in vitro

“…Vascular inflammation, fostered by inflammatory and osteogenic cytokines as tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), promotes the development of vascular calcification [11]. The increased risk of mortality in these patients is associated with increased levels of the proinflammatory cytokine growth differentiation factor 15 (GDF-15) [12]. The insufficient removal of osteogenic cytokines using conventional haemodialysis membranes may therefore support the excessive calcification of end-stage renal disease patients.…”