Osteoprotegerin and RANKL Serum Levels and Their Relationship with Serum Ghrelin in Children with Chronic Renal Failure and on Dialysis

Abstract

Background: Osteoprotegerin (OPG) and receptor activator of the nuclear factor ĸB ligand (RANKL) constitute a complex system of mediators involved in the regulation of bone resorption process. Ghrelin, a growth hormone secretagogue, has been shown to modulate proliferation and differentiation of osteoblasts. The present study was carried out to evaluate the serum concentrations of OPG and sRANKL in children with chronic renal impairment (CRI) and on dialysis, and to establish a possible relationship between their serum levels and that of ghrelin. Methods: 33 patients including 10 patients with CRI, 12 peritoneal dialysis (PD) and 11 hemodialysis (HD) patients and 22 healthy controls were enrolled into the study. OPG, sRANKL and ghrelin levels were studied with radioimmunoassay. Results: Serum OPG levels in CRI, PD and HD groups were significantly higher than the healthy controls (p = 0.002, p < 0.001, p < 0.001, respectively) whereas sRANKL levels were significantly lower than the healthy controls (p = 0.03, p = 0.01, p = 0.001, respectively). Ghrelin levels were significantly higher in CRI, PD and HD groups compared to healthy controls (p = 0.001, p < 0.001, p < 0.001, respectively). We observed a negative correlation between the sRANKL and OPG levels (r = –0.27, p = 0.04) as well as between sRANKL and ghrelin levels (r = –0.31, p = 0.02). OPG levels showed a positive correlation with ghrelin levels (r = 0.63, p < 0.001). Conclusion: We found a lower RANKL bioactivity index in children with CRI and on dialysis. The mechanism and the role of elevated OPG and low sRANKL in uremia are unclear, but they might partly represent a compensatory mechanism to the negative balance of bone remodeling in renal bone disease in children. Additionally, we demonstrated for the first time that ghrelin and the RANKL/OPG system have a close relationship in CRF. Therefore, ghrelin may be of importance in mediating the effects of the RANKL/OPG system in renal bone disease.

Plasma levels of acylated and total ghrelin in pediatric patients with chronic kidney disease

“…These findings are in keeping with other studies [23][24][25]. In the total group of uremic patients, total ghrelin levels revealed an inverse correlation with GFR, and multiple regression analysis confirmed GFR as a negative predictor of total ghrelin.…”

“…Elevated levels of total ghrelin have been demonstrated in children with CKD in three studies [23][24][25], and a negative correlation between total ghrelin and glomerular filtration rate has been shown in CKD children [23]. To the best of our knowledge, acyl ghrelin has been measured in only one pediatric study, which reported unaltered levels [26].…”

Simultaneous quantification of acylated and desacylated ghrelin in biological fluids

“…Furthermore, the concentrations found here were substantially higher than the average ghrelin level (about 324-490 pg mL −1 ) found in the plasma of fasting humans, while they were similar to acylated ghrelin levels (about 33-70 pg mL −1 ) in human plasma (Kojima and Kangawa, 2005;Kitamura et al, 2003). It is known that the normal range of ghrelin varies with methodology used (Ozkaya et al, 2007;Kierson et al, 2006). Although it was not among the objectives of the study here, we also found that urine acylated and desacylated ghrelin were 3-and 60-fold higher, respectively, than human plasma ghrelin levels (Kojima and Kangawa, 2005;Groschl et al, 2004).…”

Association of Plasma Des-acyl Ghrelin Levels with CKD

“…Increased levels of TG with decreasing GFR have been reported by others (15)(16)(17)(18)(19)21,26) as well as variable removal by dialysis (16,18,21). Some studies reported a decrease in both AG and DG (16,18) by hemodialysis that would not be expected for AG, which is highly bound to large plasma molecules such as lipoprotein (27,28).…”