Predictive ability

In a prospective trial with 412 HD patients, CVD incidence was recorded over the course of three years (Intern Med 2010;49:2057-2064). Stratifying groups by low and high acyl ghrelin levels, acylated ghrelin and total ghrelin demonstrated significant hazard ratios for CVD after multivariate analysis. Low acylated ghrelin increased risk while high total ghrelin increased risk.

The authors attributed these findings to the anti-inflammatory effects of acyl ghrelin and the potential protective effect this has on endothelial tissues. Of note, high levels of total ghrelin correlate with tumor necrosis factor-alpha and interleukin-6 which is most likely due to increases in obestatin and des-acyl ghrelin.

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In another study, total ghrelin was measured in 217 dialysis patients who were followed up for 20-38 months. Low ghrelin values were associated with increased risk for CVD-related mortality. When factoring ghrelin levels and PEW factors, the risk for all-cause and CVD related mortality more than doubled in the low ghrelin, PEW patients.

In a group of failed renal transplant patients, significantly elevated serum total ghrelin levels, elevated inflammatory factors, and low albumin were found in the failed transplant group (J Ren Nutr. 2012 Mar;22(2):258-67. doi: 10.1053/j.jrn.2011.07.005. Epub 2011 Nov 3).

Nutritional interventions

At this time, the application of ghrelin for nutritional assessment or interventions requires further research. On the other hand, ghrelin appears to be a more promising nutritional indicator than leptin. Of note, recent group studied the effect of intradialytic oral nutritional supplementation (IDON) and intradialytic parenteral nutritional supplementation (IDPN) on hormonal responses, including insulin, ghrelin, and glucagon-like peptide 1 in HD patients over four weeks (Am J Nephrol 2010;32:272-278).

Although dialysis sessions reduced total ghrelin levels in all study groups, the total ghrelin in the IDPN group was significantly lower than that of the control group, whereas the IDON group was not significantly different from either.

These results indicate that the nutritional contribution of IDPN does have an effect beyond that of dialysis-related clearance alone, and the mechanism is most likely through hormonal cascades, possibly related to insulin. The blunted effect in IDON may be related to the increased time required for digestion or hormonal regulators of ghrelin secretion in the stomach and small intestine not triggered by parenteral administration.

More research needs to be done on the predictive ability of ghrelin as a nutritional outcome in renal patients. At this time, it appears that ghrelin could offer not only a good outcome measure, but a pharmaceutical outlet for managing PEW and anorexia in renal disease patients.