Ghrelin is a hormone secreted by the stomach and small intestine. Three forms exist: acyl ghrelin exerting orexigenic effects, and des-acyl ghrelin and obestatin exerting anorexigenic effects (Pediatr Nephrol 2013;28:611-616).

Ghrelin is metabolized by the kidney; thus serum levels are elevated in chronic kidney disease (CKD) populations, up to three times in end-stage renal disease (ESRD) patients. More specifically, acyl-ghrelin levels are the same as controls, but the ratio of acyl ghrelin and total ghrelin is decreased. This hormonal profile promotes an anorexigenic response. Acyl/total ghrelin levels positively correlate with albumin and negatively correlate with CKD stage and growth hormone.

Rodent studies have found that ghrelin administration decreases muscle protein degradation and reduces inflammatory cytokines. Furthermore, rodent ghrelin infusions have improved oral food intake and lean body mass (Endocrinology 2008;149:827-835). The ghrelin infusion was also found to improve transcription factors associated with lipid metabolism, that, as a result, decreased muscle triglyceride concentrations (Kidney Int 2010;77:23-28).

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Additionally, ghrelin has been found to have positive impacts on cardiovascular related outcomes in rodent models. Conversely, inflammation has been shown to decrease ghrelin levels, and thus the reduction of ghrelin in response to inflammatory markers may make it a target for cardiovascular disease (CVD) risk assessment.

Various rodent studies have found improvements in many CVD-related factors after ghrelin administration, including cardiac cachexia (Basic Res Cardiol 2003;98:401-405).

Observational data

In hemodialysis (HD) cohorts, studies have shown associations between low acyl ghrelin levels and protein-energy wasting (PEW) and between increased levels of des-acyl ghrelin and anorexia. In a study of 50 HD patients who were compared with healthy controls, the two groups had similar acyl ghrelin levels, whereas des-acyl ghrelin was elevated (Nutrition 2010;26:1100-1104). Interestingly, as BMI increased in these patients, acyl ghrelin increased, but obestatin decreased.

These results indicate that although the levels of the orexigenic ghrelin form remain similar between healthy patients and HD patients, the increased levels of anorexigenic ghrelin may be related to decreased appetite that caused or resulted from reduced BMI.

Several studies have confirmed this trend of elevated total ghrelin levels but normal to low acyl ghrelin concentrations (Pediatr Nephrol 2010;25:2477-2482) (J Ren Nutr. 2010 May;20(3):151-7. doi: 10.1053/j.jrn.2009.08.007. Epub 2009 Nov 12) (Pediatr Nephrol 2010;25:2295-2301). Des-acyl ghrelin levels are shown to negatively correlate with protein intake while acyl-ghrelin levels negatively correlate with CRP. Primary predictors of total ghrelin levels are age and GFR. Acute administration of subcutaneous injections of acyl ghrelin increase serum ghrelin, decreased blood pressure for two hours, increase appetite, and increase energy intake (Kidney Int 2009;76:199-206).