To the best of our knowledge there is only scarce data in the literature regarding the fate of ZAG in the body. The actual turnover rate of ZAG in plasma is to date unknown. Many works documented the increase in plasma concentration of cytokines and hormones such as adiponectin and leptin in ESRD subjects. Indeed, leptin is cleared from the bloodstream by the kidney through glomerular filtration followed by metabolic degradation in the renal tubules. Normal renal function removes 12% of circulating leptin while in patients with CKD, there is virtually no renal uptake of leptin. If ZAG breakdown GW-572016 occurs as it has been described for leptin in renal tubules, a decrease in GFR and/ or tubular reabsorption could explain the rise of plasma ZAG concentration observed in CKD patients. An alternative hypothesis is that ZAG secretion could be specifically increased in uremic subjects. Supporting this idea, we recently demonstrated that uremic plasma stimulates ZAG production by adipocytes in vitro and that 5/6 nephrectomized rodents exhibited a significantly increased ZAG protein content in WAT associated with a significant decrease in WAT deposition. We further showed that subcutaneous white adipose tissue biopsies from patients with end-stage renal disease exhibited a higher content of ZAG than age-matched controls, raising the hypothesis that deregulation of ZAG secretion could also contribute to the increased plasma ZAG concentration reported ESRD patients. Although Ryden et al reported that there was no significant contribution of WAT to the circulating levels of ZAG, we can hypothesize that an up-regulation of ZAG production by some tissues could contribute to the increased plasma ZAG concentration. We noticed that plasma ZAG concentration increased during HD independently of hemoconcentration suggesting that additional ZAG is secreted in the organism during HD process. Inflammation, shear stress, oxidative stress, catecholamine secretion or lack of biocompatibility, associated with HD could enhance ZAG secretion. In good agreement, we found a significant increase in plasma ZAG concentration in post-HD patient compared to PD patients. This result suggests that the increase in circulating ZAG that occurs during HD process is related to factors that are lacking in PD. Glucocorticoids are described to increase ZAG secretion. And cortisol level has been shown to be increased by hemodialysis session suggesting that glucocorticoids could enhance ZAG secretion and contribute to the perdialytic increase in plasma ZAG concentration.