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Age modifies the association between serum obestatin, appetite and nutritional status in maintenance hemodialysis patients

European Journal of Clinical Nutrition volume 72, pages 1007–1018 (2018)Cite this article

Subjects

Abstract

Background/objectives

Increased age is strongly associated with anorexia and protein-energy wasting (PEW) in maintenance hemodialysis (MHD) population. We hypothesized that the association of obestatin, a recently discovered anorexigenic gut hormone, with appetite and nutritional status differs by age groups.

Subjects/methods

We performed a cross-sectional study on 261MHD patients. Obestatin, acyl-ghrelin, markers of inflammation (CRP, IL-6, TNF-α) and nutrition (self-reported appetite, dietary intake, biochemical nutritional parameters, and body composition) were measured.

Results

Obestatin was associated with appetite in multivariate analyses even after controlling for such confounders as lean body mass (LBM), IL-6 and acyl-ghrelin in patients younger than 71 years. For each ng/ml increase in obestatin levels, the odds for diminished appetite was 0.75 (95% CI: 0.59–0.96). However, these associations were not observed in patients 71 years and older. Multivariable logistic regression models (including appetite) also showed increasing odds for PEW (defined by ESPEN consensus-based criteria for the diagnosis of malnutrition) across increasing serum obestatin levels (OR: 1.51, 95% CI: 1.05–2.18) in patients 71 years and older. However, after lean body mass (LBM) was added to this model, the association between obestatin and malnutrition was abolished (OR: 1.26, 95% CI: 0.83–1.91).

Conclusions

The association between serum obestatin, appetite and PEW differs depending on age in MHD patients. A positive link with appetite exists in patients younger than 71 years, whereas this relationship disappears by the age of 71. In older MHD patients, obestatin is associated with PEW through mechanisms related to LBM, but not to appetite.

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References

  1. Bossola M, Tazza L, Giungi S, Luciani G. Anorexia in hemodialysis patients: an update. Kidney Int. 2006;70:417–22.

    Article  CAS  Google Scholar 

  2. Zhang JV, Ren PG, Avsian-Kretchmer O, Luo CW, Rauch R, Klein C, et al. Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin’s effects on food intake. Science. 2005;310:996–9.

    Article  CAS  Google Scholar 

  3. Borges N, Moraes C, Barros AF, Carraro-Eduardo JC, Fouque D, Mafra D. Acyl-ghrelin and obestatin plasma levels in different stages of chronic kidney disease. J Ren Nutr. 2014;24:100–4.

    Article  CAS  Google Scholar 

  4. Xing YX, Yang L, Kuang HY, Gao XY, Liu HL. Function of obestatin in the digestive system. Nutrition. 2017;34:21–8.

    Article  CAS  Google Scholar 

  5. Depoortere I, Thijs T, Moechars D, De Smet B, Ver Donck L, Peeters TL. Effect of peripheral obestatin on food intake and gastric emptying in ghrelin-knockout mice. Br J Pharmacol. 2008;153:1550–7.

    Article  CAS  Google Scholar 

  6. Zizzari P, Longchamps R, Epelbaum J, Bluet-Pajot MT. Obestatin partially affects ghrelin stimulation of food intake and growth hormone secretion in rodents. Endocrinology. 2007;148:1648–53.

    Article  CAS  Google Scholar 

  7. Beasley JM, Ange BA, Anderson CA, Miller ER 3rd, Erlinger TP, Holbrook JT, et al. Associations between macronutrient intake and self-reported appetite and fasting levels of appetite hormones: results from the Optimal Macronutrient Intake Trial to Prevent Heart Disease. Am J Epidemiol. 2009;169:893–900.

    Article  Google Scholar 

  8. Mafra D, Guebre-Egziabher F, Cleaud C, Arkouche W, Mialon A, Drai J, et al. Obestatin and ghrelin interplay in hemodialysis patients. Nutrition. 2010;26:1100–4.

    Article  CAS  Google Scholar 

  9. Lacquaniti A, Bolignano D, Donato V, Chirico V, Romeo A, Loddo S, et al. Obestatin: a new element for mineral metabolism and inflammation in patients on hemodialysis. Kidney Blood Press Res. 2011;34:104–10.

    Article  CAS  Google Scholar 

  10. Beberashvili I, Sinuani I, Azar A, Kadoshi H, Shapiro G, Feldman L, et al. Low serum concentration of obestatin as a predictor of mortality in maintenance hemodialysis patients. Biomed Res Int. 2013;2013:796586.

    Article  Google Scholar 

  11. Lippl F, Erdmann J, Lichter N, Tholl S, Wagenpfeil S, Adam O, et al. Relation of plasma obestatin levels to bmi, gender, age and insulin. Horm Metab Res. 2008;40:806–12.

    Article  CAS  Google Scholar 

  12. Beasley JM, Ange BA, Anderson CA, Miller Iii ER, Holbrook JT, Appel LJ. Characteristics associated with fasting appetite hormones (obestatin, ghrelin, and leptin). Obes (Silver Spring). 2009;17:349–54.

    Article  CAS  Google Scholar 

  13. Wolfson M. Nutrition in elderly dialysis patients. Semin Dial. 2002;15:113–5.

    Article  Google Scholar 

  14. Johansson L. Nutrition in older adults on peritoneal dialysis. Perit Dial Int. 2015;35:655–8.

    Article  CAS  Google Scholar 

  15. Burrowes JD, Cockram DB, Dwyer JT, Larive B, Paranandi L, Bergen C, et al. Cross-sectional relationship between dietary protein and energy intake, nutritional status, functional status, and comorbidity in older versus younger hemodialysis patients. J Ren Nutr. 2002;12:87–95.

    Article  Google Scholar 

  16. Ohkawa S, Odamaki M, Ikegaya N, Hibi I, Miyaji K, Kumagai H. Association of age with muscle mass, fat mass and fat distribution in non-diabetic haemodialysis patients. Nephrol Dial Transplant. 2005;20:945–51.

    Article  Google Scholar 

  17. Beberashvili I, Sinuani I, Azar A, Shapiro G, Feldman L, Stav K, et al. Serum uric acid as a clinically useful nutritional marker and predictor of outcome in maintenance hemodialysis patients. Nutrition. 2015;31:138–47.

    Article  CAS  Google Scholar 

  18. Fouque D, Vennegoor M, ter Wee P, Wanner C, Basci A, Canaud B. et al. EBPG guideline on nutrition. Nephrol Dial Transplant. 2007;22:ii45–87.

    Article  Google Scholar 

  19. Depner TA, Daugirdas JT. Equations for normalized protein catabolic rate based on two-point modeling of hemodialysis urea kinetics. J Am Soc Nephrol. 1996;7:780–5.

    CAS  PubMed  Google Scholar 

  20. Rambod M, Bross R, Zitterkoph J, Benner D, Pithia J, Colman S, et al. Association of Malnutrition-Inflammation Score with quality of life and mortality in hemodialysis patients: a 5-year prospective cohort study. Am J Kidney Dis. 2009;53:298–309.

    Article  Google Scholar 

  21. Beberashvili I, Azar A, Sinuani I, Kadoshi H, Shapiro G, Feldman L, et al. Comparison analysis of nutritional scores for serial monitoring of nutritional status in hemodialysis patients. Clin J Am Soc Nephrol. 2013;8:443–51.

    Article  CAS  Google Scholar 

  22. Yamada K, Furuya R, Takita T, Maruyama Y, Yamaguchi Y, Ohkawa S, et al. Simplified nutritional screening tools for patients on maintenance hemodialysis. Am J Clin Nutr. 2008;87:106–13.

    Article  CAS  Google Scholar 

  23. Cederholm T, Bosaeus I, Barazzoni R, Bauer J, Van Gossum A, Klek S, et al. Diagnostic criteria for malnutrition - An ESPEN consensus statement. Clin Nutr. 2015;34:335–40.

    Article  CAS  Google Scholar 

  24. Liu J, Huang Z, Gilbertson DT, Foley RN, Collins AJ. An improved comorbidity index for outcome analyses among dialysis patients. Kidney Int. 2010;77:141–51.

    Article  Google Scholar 

  25. Kyle UG, Bosaeus I, De Lorenzo AD, Deurenberg P, Elia M, Manuel Gómez J, et al. ESPEN. Bioelectrical impedance analysis-part II: utilization in clinical practice. Clin Nutr. 2004;23:1430–53.

    Article  Google Scholar 

  26. Kyle UG, Genton L, Karsegard L, Slosman DO, Pichard C. Single prediction equation for bioelectrical impedance analysis in adults aged 20--94 years. Nutrition. 2001;17:248–53.

    Article  CAS  Google Scholar 

  27. Hassouna R, Zizzari P, Tolle V. The ghrelin/obestatin balance in the physiological and pathological control of growth hormone secretion, body composition and food intake. J Neuroendocrinol. 2010;22:793–804.

    CAS  PubMed  Google Scholar 

  28. Bossola M, Muscaritoli M, Valenza V, Panocchia N, Tazza L, Cascino A, et al. Anorexia and serum leptin levels in hemodialysis patients. Nephron Clin Pract. 2004;97:c76–82.

    Article  CAS  Google Scholar 

  29. Wright M, Woodrow G, O’Brien S, King N, Dye L, Blundell J, et al. Disturbed appetite patterns and nutrient intake in peritoneal dialysis patients. Perit Dial Int. 2003;23:550–6.

    PubMed  Google Scholar 

  30. Chang CC, Chen HL, Hung CH, Hwang KL, Lin CY. Single meal food intake characteristics reliably predict nutrition status and body composition in patients undergoing continuous peritoneal dialysis. Nephrol (Carlton). 2007;12:337–41.

    Article  Google Scholar 

  31. Germain N, Galusca B, Grouselle D, Frere D, Billard S, Epelbaum J, et al. Ghrelin and obestatin circadian levels differentiate bingeing-purging from restrictive anorexia nervosa. J Clin Endocrinol Metab. 2010;95:3057–62.

    Article  CAS  Google Scholar 

  32. Caliskan Y, Yelken B, Gorgulu N, Ozkok A, Yazici H, Telci A, et al. Comparison of markers of appetite and inflammation between hemodialysis patients with and without failed renal transplants. J Ren Nutr. 2012;22:258–67.

    Article  CAS  Google Scholar 

  33. Ashby DR, Ford HE, Wynne KJ, Wren AM, Murphy KG, Busbridge M, et al. Sustained appetite improvement in malnourished dialysis patients by daily ghrelin treatment. Kidney Int. 2009;76:199–206.

    Article  CAS  Google Scholar 

  34. Hung AM, Ikizler TA. Factors determining insulin resistance in chronic hemodialysis patients. Contrib Nephrol. 2011;171:127–34.

    Article  CAS  Google Scholar 

  35. Germain N, Galusca B, Grouselle D, Frere D, Tolle V, Zizzari P, et al. Ghrelin/obestatin ratio in two populations with low body weight: constitutional thinness and anorexia nervosa. Psychoneuroendocrinology. 2009;34:413–9.

    Article  CAS  Google Scholar 

  36. Guo ZF, Zheng X, Qin YW, Hu JQ, Chen SP, Zhang Z. Circulating preprandial ghrelin to obestatin ratio is increased in human obesity. J Clin Endocrinol Metab. 2007;92:1875–80.

    Article  CAS  Google Scholar 

  37. Mafra D, Guebre-Egziabher F, Fouque D. Endocrine role of stomach in appetite regulation in chronic kidney disease: about ghrelin and obestatin. J Ren Nutr. 2010;20:68–73.

    Article  CAS  Google Scholar 

  38. Wright MJ, Woodrow G, O’Brien S, King NA, Dye L, Blundell JE, et al. A novel technique to demonstrate disturbed appetite profiles in haemodialysis patients. Nephrol Dial Transplant. 2001;16:1424–9.

    Article  CAS  Google Scholar 

  39. Fassett RG1, Robertson IK, Geraghty DP, Ball MJ, Coombes JS. Dietary intake of patients with chronic kidney disease entering the LORD trial: adjusting for underreporting. J Ren Nutr. 2007;17:235–42.

    Article  Google Scholar 

  40. Biasioli S, Foroni R, Petrosino L, Cavallini L, Zambello A, Cavalcanti G, et al. Effect of aging on the body composition of dialyzed subjects. Comparison with normal subjects. ASAIO J. 1993;39:M596–601.

    CAS  PubMed  Google Scholar 

  41. Nolph KD, Moore HL, Prowant B, Meyer M, Twardowski ZJ, Khanna R, et al. Age and indices of adequacy and nutrition in CAPD patients. Adv Perit Dial. 1993;9:87–91.

    CAS  PubMed  Google Scholar 

  42. Harper EJ. Changing perspectives on aging and energy requirements: aging and energy intakes in humans, dogs and cats. J Nutr. 1998;128:2623S–6S.

    Article  CAS  Google Scholar 

  43. Roberts SB, Fuss P, Heyman MB, Young VR. Influence of age on energy requirements. Am J Clin Nutr. 1995;62:1053S–8S.

    Article  CAS  Google Scholar 

  44. Eftekhari MH, Ranjbar-Zahedani M, Basiratnia M, Rezaianzadeh A, Faghih S. Comparison of appetite-regulating hormones and body composition in pediatric patients in predialysis stage of chronic kidney disease and healthy control group. Iran J Med Sci. 2015;40:27–33.

    PubMed  PubMed Central  Google Scholar 

  45. Zamrazilová H, Hainer V, Sedlácková D, Papezová H, Kunesová M, et al. Plasma obestatin levels in normal weight, obese and anorectic women. Physiol Res. 2008;57:S49–55.

    PubMed  Google Scholar 

  46. Mora M, Granada ML, Palomera E, Serra-Prat M, Puig-Domingo M, Mataró Ageing Study Group.. Obestatin is associated to muscle strength, functional capacity and cognitive status in old women. Age (Dordr). 2013;35:2515–23.

    Article  CAS  Google Scholar 

  47. Wang YW, Lin TY, Peng CH, Huang JL, Hung SC. Factors Associated with Decreased Lean Tissue Index in Patients with Chronic Kidney Disease. Nutrients. 2017;9:5.

    Google Scholar 

  48. Pupim LB, Heimbürger O, Qureshi AR, Ikizler TA, Stenvinkel P. Accelerated lean body mass loss in incident chronic dialysis patients with diabetes mellitus. Kidney Int. 2005;68:2368–74.

    Article  Google Scholar 

  49. Kim JK, Choi SR, Choi MJ, Kim SG, Lee YK, et al. Prevalence of and factors associated with sarcopenia in elderly patients with end-stage renal disease. Clin Nutr. 2014;33:64–8.

    Article  Google Scholar 

  50. Feng DD, Yang SK, Loudes C, Simon A, Al-Sarraf T, Culler M, et al. Ghrelin and obestatin modulate growth hormone-releasing hormone release and synaptic inputs onto growth hormone-releasing hormone neurons. Eur J Neurosci. 2011;34:732–44.

    Article  Google Scholar 

  51. Fuoco D, Kilgour RD, Vigano A. A hypothesis for a possible synergy between ghrelin and exercise in patients with cachexia: Biochemical and physiological bases. Med Hypotheses. 2015;85:927–33.

    Article  CAS  Google Scholar 

  52. Anderwald-Stadler M, Krebs M, Promintzer M, Mandl M, Bischof MG, Nowotny P, et al. Plasma obestatin is lower at fasting and not suppressed by insulin in insulin-resistant humans. Am J Physiol Endocrinol Metab. 2007;293:E1393–8.

    Article  CAS  Google Scholar 

  53. Hung AM, Ikizler TA. Factors determining insulin resistance in chronic hemodialysis patients. Contrib Nephrol. 2011;171:127–34.

    Article  CAS  Google Scholar 

  54. Huda MS, Durham BH, Wong SP, Deepak D, Kerrigan D, McCulloch P, et al. Plasma obestatin levels are lower in obese and post-gastrectomy subjects, but do not change in response to a meal. Int J Obes (Lond). 2008;32:129–35.

    Article  CAS  Google Scholar 

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Acknowledgements

The authors appreciate the language editing of Dr. Mechael Kanovsky, which has greatly improved the manuscript.

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Authors and Affiliations

  1. Nephrology Division, Assaf Harofeh Medical Center, Zerifin, Affiliated to Sackler Faculty of Medicine Tel Aviv University, Tel Aviv, Israel

    Anna Katkov, Gregory Shapiro, Shai Efrati & Ilia Beberashvili

  2. Pathology Department, Assaf Harofeh Medical Center, Zerifin, Affiliated to Sackler Faculty of Medicine Tel Aviv University, Tel Aviv, Israel

    Inna Sinuani

  3. Nutrition Department, Assaf Harofeh Medical Center, Zerifin, Affiliated to Sackler Faculty of Medicine Tel Aviv University, Tel Aviv, Israel

    Ada Azar

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Correspondence to Ilia Beberashvili.

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Katkov, A., Sinuani, I., Azar, A. et al. Age modifies the association between serum obestatin, appetite and nutritional status in maintenance hemodialysis patients. Eur J Clin Nutr 72, 1007–1018 (2018). https://doi.org/10.1038/s41430-018-0087-0

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