Serum levels of the adipokine zinc-alpha2-glycoprotein (ZAG) predict mortality in hemodialysis patients

Abstract

Wasting has been associated with increased cardiovascular and all-cause mortality in chronic kidney disease (CKD). We investigated whether serum zinc-alpha2-glycoprotein (ZAG), a potent cachectic and lipid-mobilizing factor that is increased in patients with CKD, predicts clinical outcomes in patients on chronic hemodialysis. We quantified serum ZAG at baseline in a prospective cohort of 252 patients undergoing maintenance hemodialysis. Serum ZAG concentrations were inversely associated with serum albumin, creatinine, and triglycerides and, conversely, positively associated with age. Although ZAG is strongly linked to protein energy wasting (PEW) in patients with cancer, higher ZAG concentrations were not associated with PEW in our cohort. During a mean study follow-up of 954 days, 49 patients died and 62 patients experienced a cardiovascular event. Kaplan-Meier analysis revealed a significant correlation between serum ZAG concentrations and all-cause mortality and cardiovascular events. In separate multivariable Cox regression models, serum ZAG concentrations remained significantly associated with all-cause mortality and cardiovascular events after adjustment for demographic factors (age, sex, and dialysis vintage), metabolic parameters (serum albumin, prealbumin, triglycerides, cholesterol, normalized protein catabolic rate, and body mass index), and cardiovascular risk factors (diabetes, dyslipidemia, history of cardiovascular disease, smoking, and diuretic use as a proxy of residual renal function). Thus, serum ZAG appears to be a strong and independent predictor of mortality and cardiovascular events in patients with end-stage renal disease. Further studies are necessary to confirm this association and to elucidate the underlying mechanisms.Kidney International (2018) 94, 983-992; https://doi.

Serum copeptin and zinc-α2-glycoprotein levels are novel biomarkers of tolvaptan treatment in decompensated cirrhotic patients with ascites.

“…Zinc-alpha-2-glycoperotein (ZAG) is a 41-kDa glycoprotein synthesized by epithelial cells and adipocytes and plays a role in lipid metabolism, cell cycling and cancer progression. Serum ZAG levels has been reported as a biomarker of renal injury and can predict mortality in hemodialysis patients 5 . However, these changes in serum ZAG levels have not been reported in LC patients with ascites.…”

Identification of Dysregulated Complement Activation Pathways Driven by N-Glycosylation Alterations in T2D Patients

“…As an adipokine, ZAG is mainly secreted by subcutaneous and visceral adipocytes and is involved in stimulating adipocytes to induce lipid degradation (Yang et al, 2013). It has been reported that ZAG is related to the markers of insulin resistance or obesity and may play a role in the pathogenesis of insulin resistance (IR) (Bouchara et al, 2018). ZAG index can be served as an indicator to identify IR (Qu et al, 2016).…”

Changes in AZGP1 Serum Levels and Correlation With Pulse Wave Velocity After Kidney Transplantation

“…Although kidney transplantation offers clear survival benefits compared to dialysis, CVD remains one of the leading causes of premature death after transplantation ( 22 ). As AZGP1 has been identified as a potential modifier of CVD ( 14 – 16 ), we first assessed serum AZGP1 changes after kidney transplantation over a period of 2 years. We found a continuous decline in AZGP1, which paralleled eGFR improvement.…”

“…Importantly, there is a discrepancy in reported effects of AZGP1 on CVD between patients with and without chronic kidney disease (CKD). While higher AZGP1 levels were associated with reduced incidence of coronary heart disease and atherosclerosis in non-CKD patients (14,15), higher AZGP1 levels were shown to correlate positively with CVD in ESRD patients (16). It is therefore interesting, that so far, AZGP1 has not been investigated in the context of kidney transplantation.…”