Increased Plasma Ghrelin Levels in Chronic Renal Failure are not Associated with Hemodynamic Parameters

Abstract

Background/Aims: Hardly anything is known about the effect of renal function on plasma ghrelin levels. Ghrelin is an orexigenic hormone with important hemodynamic effects. We examined differences in plasma ghrelin levels between chronic renal failure (CRF) patients and healthy subjects, and ghrelin’s relationship with indices of left ventricular (LV) function. Methods: Fasting total plasma ghrelin levels were measured in 122 CRF patients (57 on, 65 not on hemodialysis) and 57 control subjects. Indices of LV function were evaluated using echocardiography. Results: Total plasma ghrelin levels were higher in patients with CRF compared to controls, but were not different between patients on and those not on hemodialysis. In a multivariate linear regression model, presence of kidney dysfunction explained 41 % of the variability of ghrelin values. The etiology of renal failure (diabetic nephropathy or not) had no influence on ghrelin levels in the renal patients. Ghrelin levels were not associated with indices of LV systolic function or blood pressure in these patients. Conclusion: Fasting plasma ghrelin concentrations are higher in CRF patients regardless of their need for hemodialysis compared to controls. The etiology of renal failure does not have any effect on plasma ghrelin levels. In addition, ghrelin levels are not associated with hemodynamic parameters in patients with CRF.

Key words

Peptides - Renal function - Hemodialysis - Blood pressure - Cardiac function

References

• 1 Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a novel growth hormone releasing acylated peptide from stomach.  Nature. 1999;  402 656-660
• 2 Gnanapavan S, Kola B, Bustin S A, Morris D G, McGee P, Fairclough P, Bhattacharya S, Carpenter R, Grossman A B, Korbonits M. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans.  J Clin Endocrinol Metab. 2002;  87 2988
• 3 Broglio F, Arvat E, Benso A, Gottero C, Muccioli G, Papotti M, van der Lely A J, Deghenghi R, Ghigo E. Ghrelin, a natural GH secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans.  J Clin Endocrinol Metab. 2001;  86 5083-5086
• 4 Shintani M, Ogawa Y, Ebihara K, Aizawa-Abe M, Miyanaga F, Takaya K, Hayashi T, Inoue G, Hosoda K, Kojima M, Kangawa K, Nakao K. Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway.  Diabetes. 2001;  50 227-232
• 5 Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, Matsukura S. A role for ghrelin in the central regulation of feeding.  Nature. 2001;  409 194-198
• 6 Dhillo W S, Bloom S R. Gastrointestinal hormones and regulation of food intake.  Horm Metab Res. 2004;  36 846-851
• 7 Cummings D E, Purnell J Q, Frayo R S, Schmidova K, Wisse B E, Weigle D S. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans.  Diabetes. 2001;  50 1714-1719
• 8 Shiiya T, Nakazato M, Mizuta M, Date Y, Mondal M S, Tanaka M, Nozoe S, Hosoda H, Kangawa K, Matsukura S. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion.  J Clin Endocrinol Metab. 2002;  87 240-244
• 9 Nagaya N, Uematsu M, Kojima M, Date Y, Nakazato M, Okumura H, Hosoda H, Shimizu W, Yamagishi M, Oya H, Koh H, Yutani C, Kangawa K. Elevated circulating level of ghrelin in cachexia associated with chronic heart failure: relationships between ghrelin and anabolic/catabolic factors.  Circulation. 2001;  104 2034-2038
• 10 Cummings D E, Weigle D S, Frayo R S, Breen P A, Ma M K, Dellinger E P, Purnell J Q. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery.  N Engl J Med. 2002;  346 1623-1630
• 11 Volante M, Allia E, Gugliotta P, Funaro A, Broglio F, Deghenghi R, Muccioli G, Ghigo E, Papotti M. Expression of ghrelin and of the GH secretagogue receptor by pancreatic islet cells and related endocrine tumors.  J Clin Endocrinol Metab. 2002;  87 1300-1308
• 12 Date Y, Nakazato M, Hashiguchi S, Dezaki K, Mondal M S, Hosoda H, Kojima M, Kangawa K, Arima T, Matsuo H, Yada T, Matsukura S. Ghrelin is present in pancreatic alpha-cells of humans and rats and stimulates insulin secretion.  Diabetes. 2002;  51 124-129
• 13 Mori K, Yoshimoto A, Takaya K, Hosoda K, Ariyasu H, Yahata K, Mukoyama M, Sugawara A, Hosoda H, Kojima M, Kangawa K, Nakao K. Kidney produces a novel acylated peptide, ghrelin.  FEBS Lett. 2000;  486 213-216
• 14 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;  13 2748-2752
• 15 Rodriguez Ayala E, Pecoits-Filho R, Heimburger O, Lindholm B, Nordfors L, Stenvinkel P. Associations between plasma ghrelin levels and body composition in end-stage renal disease: a longitudinal study.  Nephrol Dial Transplant. 2004;  19 421-426
• 16 Scharer K, Schmidt K G, Soergel M. Cardiac function and structure in patients with chronic renal failure.  Pediatr Nephrol. 1999;  13 951-965
• 17 Raine A EG, Schwarz U, Ritz E. Hypertension and cardiac problems. in: Oxford Textbook of Clinical Nephrology, 2nd edn. Oxford; Oxford University Press 1998: 1885-1918
• 18 Nagaya N, Kojima M, Uematsu M, Yamagishi M, Hosoda H, Oya H, Hayashi Y, Kangawa K. Hemodynamic and hormonal effects of human ghrelin in healthy volunteers.  Am J Physiol Regulatory Integrative Comp Physiol. 2001;  280 R1483-R1487
• 19 Nagaya N, Miyatake K, Uematsu M, Oya H, Shimizu W, Hosoda H, Kojima M, Nakanishi N, Mori H, Kangawa K. Hemodynamic, renal, and hormonal effects of ghrelin infusion in patients with chronic heart failure.  J Clin Endocrinol Metab. 2001;  86 5854-5859
• 20 National Kidney Foundation . K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification.  Am J Kidney Dis. 2002;  39 (2 Suppl 1) S1-S266
• 21 World Medical Association Declaration of Helsinki . Recommendations guiding physicians in biomedical research involving human subjects.  JAMA. 1997;  277 925-926
• 22 The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure: the JNC 7 Report . .  JAMA. 2003;  289 2560-2571
• 23 Nishimura R A, Miller F A Jr, Callahan M J, Benassi R C, Seward J B, Tajik A J. Doppler echocardiography: theory, instrumentation, technique, and application.  Mayo Clinic Proc. 1985;  60 321-343
• 24 Tei C, Ling L H, Hodge D O, Bailey K R, Oh J K, Rodeheffer R J, Tajik A J, Seward J B. New index of combined systolic and diastolic myocardial performance: a simple and reproducible measure of cardiac function - a study in normals and dilated cardiomyopathy.  J Cardiol. 1995;  26 357-366
• 25 Devereux R B, Reichek N. Echocardiographic determination of left ventricular mass in man: anatomic validation of the method.  Circulation. 1977;  55 613-618
• 26 Friedewald W T, Levy R I, Fredrickson D S. Estimation of the concentration of low density lipoprotein cholesterol in plasma, without use of the preparative ultracentifuge.  Clin Chem. 1972;  18 499-502
• 27 Matthews D R, Hosker J P, Rudenski A S, Naylor B A, Treacher D F, Turner R C. Homeostasis model assessment: insulin resistance and b-cell function from fasting plasma glucose and insulin concentrations in man.  Diabetologia. 1985;  28 412-419
• 28 Cockroft D, Gault M H. Prediction of creatinine clearance from serum creatinine.  Nephron. 1976;  16 31-41
• 29 Toshinai K, Mondal M S, Nakazato M, Date Y, Murakami N, Kojima M, Kangawa K, Matsukura S. Upregulation of ghrelin expression in the stomach upon fasting, insulin-induced hypoglycemia, and leptin administration.  Biochem Biophys Res Commun. 2001;  28 1220-1225
• 30 Gualillo O, Caminos J E, Nogueiras R, Seoane L M, Arvat E, Ghigo E, Casanueva F F, Dieguez C. Effect of food restriction on ghrelin in normal-cycling female rats and in pregnancy.  Obes Res. 2002;  10 682-687
• 31 Poykko S M, Kellokoski E, Horkko S, Kauma H, Kesaniemi Y A, Ukkola O. Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes.  Diabetes. 2003;  52 2546-2553
• 32 Mozid A M, Tringali G, Forsling M L, Hendricks M S, Ajodha S, Edwards R, Navarra P, Grossman A B, Korbonits M. Ghrelin is released from rat hypothalamic explants and stimulates corticotrophin-releasing hormone and arginine-vasopressin.  Horm Metab Res. 2003;  35 455-459
• 33 Nagueh S F. Noninvasive evaluation of hemodynamics by Doppler echocardiography.  Curr Opin Cardiol. 1999;  14 217-224