title: Interaction between acyl-ghrelin and BMI predicts clinical outcomes in hemodialysis patients.
abstract: Ghrelin, a gastric orexigenic peptide, and body mass index (BMI) are known as inversely associated to each other and are both linked to cardiovascular (CV) risk and mortality in maintenance hemodialysis (MHD) patients. However, it is unclear whether the interaction between ghrelin and BMI is associated with a risk of all-cause and CV death in this population.
  
  
  
  A prospective observational study was performed on 261 MHD outpatients (39% women, mean age 68.6 ± 13.6 years) recruited from October 2010 through April 2012, and were followed until November 2014 (median follow-up-28 months, interquartile range-19-34 months). We measured acyl-ghrelin (AG) levels, appetite, nutritional and inflammatory markers, prospective all-cause and cardiovascular (CV) mortality.
  
  
  
  During follow-up, 109 patients died, 51 due to CV causes. A significant interaction effect of high BMI and high AG (defined as levels higher than median) on all-cause mortality was found. Crude Cox HR for the product termed BMI x AG was 0.52, with a 95% confidence interval (CI): 0.29 to 0.95 (P = 0.03). Evaluating the interaction on an additive scale revealed that the combined predictive value of BMI and AG is larger than the sum of their individual predictive values (synergy index was 1.1). Across the four BMI-AG categories, the group with high BMI and high AG exhibited better all-cause and cardiovascular mortality irrespective of appetite and nutritional status (multivariable adjusted hazard ratios were 0.31, 95% CI 0.16 to 0.62, P = 0.001, and 0.35, 95% CI 0.13 to 0.91, P = 0.03, respectively). Data analyses made by dividing patients according to fat mass-AG, but not to lean body mass-AG categories, provided similar results.
  
  
  
  Higher AG levels enhance the favourable association between high BMI and survival in MHD patients irrespective of appetite, nutritional status and inflammation.
authors.affiliation: Nephrology Division, Assaf Harofeh Medical Center, Zerifin. Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. iliab@asaf.health.gov.il.
authors.forename: Ilia
authors.initials: I
authors.lastname: Beberashvili
authors.affiliation: Department of pathology, Assaf Harofeh Medical Center, Zerifin. Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Inna
authors.initials: I
authors.lastname: Sinuani
authors.affiliation: Nutrition Department, Assaf Harofeh Medical Center, Zerifin. Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ada
authors.initials: A
authors.lastname: Azar
authors.affiliation: Nephrology Division, Assaf Harofeh Medical Center, Zerifin. Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Gregory
authors.initials: G
authors.lastname: Shapiro
authors.affiliation: Nephrology Division, Assaf Harofeh Medical Center, Zerifin. Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Leonid
authors.initials: L
authors.lastname: Feldman
authors.affiliation: Nephrology Division, Assaf Harofeh Medical Center, Zerifin. Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Keren
authors.initials: K
authors.lastname: Doenyas-Barak
authors.affiliation: Urology Department, Assaf Harofeh Medical Center, Zerifin. Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Kobi
authors.initials: K
authors.lastname: Stav
authors.affiliation: Nephrology Division, Assaf Harofeh Medical Center, Zerifin. Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Shai
authors.initials: S
authors.lastname: Efrati
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001066:Appetite; D001823:Body Composition; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000401:mortality*; D002423:Cause of Death; D015897:Comorbidity; D004435:Eating; D005260:Female; D054439:Ghrelin / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000378:metabolism / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009026:Mortality; D015999:Multivariate Analysis; D009765:Obesity / Q000453:epidemiology / Q000378:metabolism*; D050177:Overweight / Q000453:epidemiology / Q000378:metabolism; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D006435:Renal Dialysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054439:Ghrelin; C508600:IL6 protein, human; D015850:Interleukin-6; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein
keywords: Acyl-ghrelin; Appetite; BMI; Fat mass; Ghrelin; Hemodialysis; Inflammation; Survival