title: Protein-energy wasting modifies the association of ghrelin with inflammation, leptin, and mortality in hemodialysis patients.
abstract: Ghrelin abnormalities contribute to anorexia, inflammation, and cardiovascular risk in hemodialysis patients, leading to worse outcome. However, ghrelin levels are influenced by the nutritional status of the individual. We hypothesized that the consequences of ghrelin alterations in hemodialysis patients are context sensitive and dependent on the presence of protein-energy wasting (PEW). In this cross-sectional study of 217 prevalent hemodialysis patients followed for 31 months, we measured ghrelin, leptin, PEW (subjective global assessment), and C-reactive protein (an index of inflammation). Compared to patients in the middle and upper tertile of ghrelin levels, those in the lowest tertile were older, had higher leptin levels and body mass index, and presented an increased mortality risk that persisted after adjustment for age, gender, and dialysis vintage. This risk was lost after correction for comorbidities. Patients with PEW and low ghrelin values had abnormally high C-reactive protein and leptin by multivariate analysis of variance, and the highest mortality risk compared to non-PEW with high ghrelin from all-cause and cardiovascular-related mortality (adjusted hazard ratios of 3.34 and 3.54, respectively). Low ghrelin values in protein-energy wasted hemodialysis patients were linked to a markedly increased cardiovascular mortality risk. Thus, since these patients were more anorectic, our results provide a clinical scenario where ghrelin therapies may be particularly useful.
authors.affiliation: Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Carrero
authors.forename: Ayumu
authors.initials: A
authors.lastname: Nakashima
authors.forename: Abdul R
authors.initials: AR
authors.lastname: Qureshi
authors.forename: Bengt
authors.initials: B
authors.lastname: Lindholm
authors.forename: Olof
authors.initials: O
authors.lastname: Heimbürger
authors.forename: Peter
authors.initials: P
authors.lastname: Bárány
authors.forename: Peter
authors.initials: P
authors.lastname: Stenvinkel
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood / Q000276:immunology / Q000401:mortality*; D016009:Chi-Square Distribution; D003430:Cross-Sectional Studies; D005260:Female; D054439:Ghrelin / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology / Q000401:mortality*; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000097:blood / Q000276:immunology / Q000401:mortality* / Q000628:therapy*; D020738:Leptin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011502:Protein-Energy Malnutrition / Q000097:blood / Q000276:immunology / Q000401:mortality*; D006435:Renal Dialysis / Q000401:mortality*; D018570:Risk Assessment; D012307:Risk Factors; D013548:Sweden; D013997:Time Factors
chemical_list: D015415:Biomarkers; C515349:GHRL protein, human; D054439:Ghrelin; D020738:Leptin; D002097:C-Reactive Protein