Association of Plasma Des-acyl Ghrelin Levels with CKD

Abstract

SummaryBackground and objectives There are no effective therapies for malnutrition in CKD/ESRD patients. This study hypothesized that ghrelin, an endogenous orexigenic hormone, would correlate with renal function and might suggest therapeutic interventions for CKD/ESRD malnutrition.Design, setting, participants, & measurements Fifty-one CKD and 15 hemodialysis patients were enrolled. Acyl ghrelin (AG) and des-acyl ghrelin (DG) were determined using separate two-site-specific assays. Leptin, insulin, growth hormone, insulin-link growth factor-1, C-reactive protein, TNF-a, and IL-6 were also measured.Results Univariate correlation analyses showed that CKD stage was highly, positively correlated with the levels of preprandial and postprandial DG and positively correlated with TNF-a, IL-6, leptin, and age. Multivariate partial-correlation analyses showed that CKD was independently associated with the proportion of preprandial and postprandial DG, whereas TNF-a, IL-6, leptin, insulin, and age were not independently associated with either. Geometric mean (GM) preprandial and postprandial AG were comparable between CKD stages #2 and .2, whereas GM preprandial DG and postprandial DG were 1.95-fold and 2.17-fold greater, respectively, for CKD stage .2 versus stage #2. DG was the dominant form of ghrelin preprandially and postprandially for both CKD stages #2 and .2. Dialysis had no effect on AG, but reduced DG by 73% to levels even lower (GM 48.7 pg/ml) than those seen postprandially in CKD stage #2 patients (GM 77.0 pg/ml).Conclusions This study shows a strong and independent correlation of DG with CKD stage. Postprandial suppression of ghrelin is impaired with reduced renal function. Hemodialysis selectively removes DG but not AG.

Severity of Gastric Mucosal Atrophy Is the Major Determinant of Plasma Ghrelin Level in Hemodialysis Patients

“…We plan to clarify the effect of H. pylori eradication on ghrelin production in HD patients in the future; for this purpose, we will study H. pylori positive HD patients after eradication therapy. The des-acyl ghrelin level in patients with renal dysfunction is higher than that in subjects with normal renal function, as observed in this study [36] . In general, desacyl ghrelin has been considered an inactive form of ghrelin and to play non-biological roles, because of lack of binding capacity to conventional ghrelin receptor.…”

Association between resistin and fibroblast growth factor 23 in patients with type 2 diabetes mellitus

“…Leptin increases with decreased renal function and is related to obesity and insulin resistance. In addition, one study reported that leptin and resistin are related in CKD patients 37 . A recent study also showed that leptin is significantly associated with FGF23 among patients on hemodialysis 38 .…”

“…Ghrelin is a growth hormone-releasing peptide that regulates appetite, carbohydrate utilization, and insulin resistance. Ghrelin levels decrease with increasing renal function and are associated with mortality in CKD patients 37 . In the present study, the association between resistin and FGF23 remained significant even after adjusting for leptin and ghrelin.…”

Unacylated ghrelin and obestatin in pediatric CKD: are they important in protein energy wasting?

“…A possible explanation for these seemingly contradicting findings is that only UAG levels were elevated in the CKD patients. For example, Gupta et al [18] analyzed AG and UAG levels in 51 CKD and 15 hemodialysis (HD) patients using two separate site-specific assays for these hormones. The results demonstrated that UAG levels increased with declining estimated glomerular filtration rate (eGFR), whereas AG levels remained unchanged.…”