GHRELIN AMELIORATES WASTING, CARDIOVASCULAR COMPLICATIONS, INFLAMMATION AND MORTALITY IN CHRONIC KIDNEY DISEASE

Abstract

Wasting, cardiovascular complications and inflammation are known risk factors associated with high mortality in patients with chronic kidney disease (CKD). Ghrelin is an appetite-regulating hormone with additional effects in the modulation of systemic inflammation and the cardiovascular system. CKD patients with low serum ghrelin have high mortality risk and may benefit the most from ghrelin therapy. Aim to investigate the effects of ghrelin on cachexia, muscle wasting, cardiovascular complications, inflammation and mortality in CKD. C56BL/6J mice underwent 2-stage 5/6 nephrectomy (CKD) or sham operation (S). Ghrelin (150 nmole/kg/day) or saline was given to CKD or S mice. Over 90-days, mortality rates of 9 month old ghrelin-treated CKD mice (15%) and S mice (0%) were significantly better than those of CKD mice (57.5%). The cumulative food intake of the CKD + ghrelin mice was significantly increased than CKD mice (p<0.01). CKD + ghrelin mice gained more weight than CKD mice (p<0.01). CKD + ghrelin mice gained lean body mass and fat mass while CKD mice lost lean and fat mass (p<0.01). 24 hr metabolic rate was increased and efficiency of food consumption was decreased in CKD mice as compared to S mice (p<0.001). Ghrelin normalized these abnormalities in CKD mice (p<0.01). Ghrelin significantly improved systolic hypertension in CKD mice (p<0.01). Left ventricular hypertrophy (LVH) was ameliorated in CKD+ghrelin mice as compared to CKD mice (p<0.01). TNF-α and IL-6 mRNA levels were significantly increased in gastrocnemius and cardiac muscles of CKD mice and ghrelin significantly decreased the expression of these inflammatory cytokines in CKD mice (p<0.01). Our studies indicate that ghrelin ameliorates wasting, systemic hypertension and LVH with associated improvement in inflammation and mortality in CKD.