Ghrelin and Obestatin in CKD Children

Chronic Kidney Diseases Clinical Trial

Official title:

Unacylated Ghrelin and Obestatin as Promising Biomarkers of Protein Energy Wasting in Children With Chronic Kidney Disease: a Cross-sectional Case-control Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03171116
• Other study ID #: 396/2011 bis
• Status: Completed
• Phase: N/A
• First received: May 25, 2017
• Last updated: May 28, 2017
• Start date: January 1, 2013
• Est. completion date: June 30, 2015

Study information

• Verified date: May 2017
• Source: Azienda Ospedaliero Universitaria Maggiore della Carita
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Protein energy wasting (PEW) is a complex syndrome associated with different underlying illnesses and characterized by loss of muscle, with or without loss of fat. It is a highly prevalent condition among patients with chronic kidney disease (CKD), associated with increased morbidity and mortality.

The pathophysiology of PEW in CKD is multifactorial and not yet completely understood. The potential role in uremic PEW of two of hormones involved in orexigenic/anorexigenic balance, ghrelin and obestatin, both derived from the ghrelin gene (GHRL), has been investigated in adults and, less extensively, in children. Aim of our study was to measure AG, UAG and obestatin concentrations in children with CKD and to assess their potential contribution to the development of pediatric uremic PEW.

Description:

This is a cross-sectional case-control study. Between January 2013 and June 2015 children and adolescents aged 5-20 years, referred to the Pediatric Nephrology, Dialysis and Transplant Unit of Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico - Milan, Italy were enrolled. Subjects with CKD stages II-V under conservative treatment (CKD-CT), or undergoing hemodialysis treatment (CKD-HD), or being renal transplant recipients (RTx) were included in the study. Data about age, primary renal disease and concomitant medications were collected for each subject.

CKD stages were defined using the K/DOQI criteria of the US National Kidney Foundation.

Control subjects were outpatients of the Pediatric Surgery Unit of the Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico - Milan, Italy, aged 1-20 years, who underwent a blood sample collection before a surgical intervention for the treatment of minor diseases that did not impair renal or endocrine function (i.e. phimosis, hydrocele, inguinal hernia).

Biochemical and hormonal parameters Blood samples were collected between 7:00 and 8:00 a.m. after an overnight fast, and before dialysis in CKD-HD patients. Routine biochemical parameters [creatinine, urea] were measured in all subjects. Glomerular filtration rate was estimated (eGFR) by the Schwartz formula, with k = 0.413, as appropriate for standardized creatinine.

In all subjects, plasma AG and UAG concentrations were measured by the Human Acylated / Unacylated Ghrelin ELISA kit (BioVendor, Laboratorni Medicina a.s., Brno, Czech Republic) according to manufacture procedures, and AG/UAG ratio was calculated. Serum obestatin concentrations were determined using the Human Obestatin ELISA kit (BioVendor, Laboratorni Medicina a.s., Brno, Czech Republic).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 154
• Est. completion date: June 30, 2015
• Est. primary completion date: June 30, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 20 Years

Eligibility

Inclusion Criteria:

• the CKD-HD patients should have been on hemodialysis treatment for at least 3 months

• the RTx patients should have received renal transplantation at least 6 months before

Exclusion Criteria:

• treatment with growth hormone

• the presence of neurologic disability or syndromic diseases affecting per se food intake

• for controls: they should have no history of chronic diseases and should not receive any medication. They should be on unrestricted diet.

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Other:
• none intervention
it is not an interventional study; it is an observational study

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliero Universitaria Maggiore della Carita

References & Publications (10)

Arbeiter AK, Büscher R, Petersenn S, Hauffa BP, Mann K, Hoyer PF. Ghrelin and other appetite-regulating hormones in paediatric patients with chronic renal failure during dialysis and following kidney transplantation. Nephrol Dial Transplant. 2009 Feb;24(2):643-6. doi: 10.1093/ndt/gfn529. Epub 2008 Sep 22. — View Citation

Barazzoni R, Zanetti M, Stulle M, Mucci MP, Pirulli A, Dore F, Panzetta G, Vasile A, Biolo G, Guarnieri G. Higher total ghrelin levels are associated with higher insulin-mediated glucose disposal in non-diabetic maintenance hemodialysis patients. Clin Nutr. 2008 Feb;27(1):142-9. Epub 2007 Sep 12. — View Citation

Büscher AK, Büscher R, Hauffa BP, Hoyer PF. Alterations in appetite-regulating hormones influence protein-energy wasting in pediatric patients with chronic kidney disease. Pediatr Nephrol. 2010 Nov;25(11):2295-301. doi: 10.1007/s00467-010-1588-9. Epub 2010 Jul 6. — View Citation

Iglesias P, Díez JJ, Fernández-Reyes MJ, Codoceo R, Alvarez-Fidalgo P, Bajo MA, Aguilera A, Selgas R. Serum ghrelin concentrations in patients with chronic renal failure undergoing dialysis. Clin Endocrinol (Oxf). 2006 Jan;64(1):68-73. — View Citation

Jarkovská Z, Hodková M, Sazamová M, Rosická M, Dusilová-Sulková S, Marek J, Justová V, Lacinová Z, Haluzík M, Haas T, Krsek M. Plasma levels of active and total ghrelin in renal failure: a relationship with GH/IGF-I axis. Growth Horm IGF Res. 2005 Dec;15(6):369-76. Epub 2005 Sep 28. — View Citation

Mafra D, Guebre-Egziabher F, Cleaud C, Arkouche W, Mialon A, Drai J, Fouque D. Obestatin and ghrelin interplay in hemodialysis patients. Nutrition. 2010 Nov-Dec;26(11-12):1100-4. doi: 10.1016/j.nut.2009.09.003. Epub 2009 Dec 16. — View Citation

Mak RH, Ikizler AT, Kovesdy CP, Raj DS, Stenvinkel P, Kalantar-Zadeh K. Wasting in chronic kidney disease. J Cachexia Sarcopenia Muscle. 2011 Mar;2(1):9-25. Epub 2011 Mar 16. — View Citation

Nüsken KD, Gröschl M, Rauh M, Stöhr W, Rascher W, Dötsch J. Effect of renal failure and dialysis on circulating ghrelin concentration in children. Nephrol Dial Transplant. 2004 Aug;19(8):2156-7. — View Citation

Pérez-Fontán M, Cordido F, Rodríguez-Carmona A, Peteiro J, García-Naveiro R, García-Buela J. Plasma ghrelin levels in patients undergoing haemodialysis and peritoneal dialysis. Nephrol Dial Transplant. 2004 Aug;19(8):2095-100. Epub 2004 Jun 8. — View Citation

Yoshimoto A, Mori K, Sugawara A, Mukoyama M, Yahata K, Suganami T, Takaya K, Hosoda H, Kojima M, Kangawa K, Nakao K. Plasma ghrelin and desacyl ghrelin concentrations in renal failure. J Am Soc Nephrol. 2002 Nov;13(11):2748-52. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AG concentrations by ELISA kit on plasma samples	Acyl-ghrelin measurement	January 2013-June 2015
Primary	UAG concentrations by ELISA kit on plasma samples	Unacyl-ghrelin measurement	January 2013-June 2015
Primary	Obestatin concentrations by ELISA kit on serum samples	Obestatin measurement	January 2013-June 2015