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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2007  |  Volume : 18  |  Issue : 2  |  Page : 173-176
Evaluation of Insulin Like growth factor-1 (IGF-1) in children with different stages of chronic renal failure


Department of Pediatrics, Shiraz University of Medical Sciences, Shiraz, Iran

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   Abstract 

Growth retardation in children with chronic kidney disease (CKD) is multifactorial that include inadequate protein and calorie intake, persistent metabolic acidosis, calcitriol deficiency, renal osteodystrophy, drug toxicity, uremic toxins, and growth factor abnormalities such as insulin-like growth factor (IGF) and IGF binding proteins. In this study, we compare the IGF-1 levels in normal and growth retarded CKD children. Serum IGF-1 levels were determined in 22 children with end-stage renal disease, 26 children with CKD at different stages, 23 children with normal height and weight for age, and 23 children with constitutionally short stature. Mean serum levels of IGF-1 were 209 ± 141 ng/ml in the ESRD group (group 1), 159 ± 163 ng/ml in the CKD group (group 2), 420 ± 182 ng/ml in normal children (group 3), and 360 ± 183 ng/ml in children with constitutional short stature (group 4). The differences in the levels of IGF-1 in groups 1 and 2 were statistically significant when compared to groups 3 and 4 (p<0.0001 and p<0.02, respectively), while the levels of IGF-1 were not statistically different between groups 1 and 2. No correlation was found between IGF-1 levels and glomerular filtration rate, height or weight in groups 1 and 2. In conclusion, serum levels of IGF-1 in children with CKD are significantly lower than healthy children.

Keywords: Insulin Like Growth factor-1, Chronic Kidney disease, Children

How to cite this article:
Derakhshan A, Karamifar H, Razavi Nejad S M, Fallahzadeh M H, Hashemi G H. Evaluation of Insulin Like growth factor-1 (IGF-1) in children with different stages of chronic renal failure. Saudi J Kidney Dis Transpl 2007;18:173-6

How to cite this URL:
Derakhshan A, Karamifar H, Razavi Nejad S M, Fallahzadeh M H, Hashemi G H. Evaluation of Insulin Like growth factor-1 (IGF-1) in children with different stages of chronic renal failure. Saudi J Kidney Dis Transpl [serial online] 2007 [cited 2020 Jun 5];18:173-6. Available from: http://www.sjkdt.org/text.asp?2007/18/2/173/32305

   Introduction Top


Children with chronic kidney disease (CKD) are often growth retarded. Growth retardation in these children is multifactorial including: inadequate protein and calorie intake, persi­stent metabolic acidosis, calcitriol deficiency, renal osteodystrophy, drug toxicity, uremic toxins and aberrant concentrations of growth factors, such as: insulin-like growth factor (IGF) and IGF binding proteins (IGFBP).[1],[2]

Growth hormone stimulates production and release of IGF-1 as well as inducing direct effects on target tissues.[3],[4],[5],[6]

In some recent reports, IGF-1 levels in uremic children were close to normal but the levels of IGFBPs were elevated due to decreased renal clearance as well as probable increased synthesis.[7],[8]

There are at least six known IGFBPs and their plasma levels are inversely related to the level of the glomerular filtration rate (GFR). These binding proteins, especially IGFBP3, act as IGF-1 inhibitors.[5],[9],[10],[11],[12]

Previous studies revealed variable levels of IGF-1 in children with CKD.[10],[13]

In this study we compare the serum IGF-1 levels in children at different stages of CKD with those in normal children and children with constitutional growth retardation.


   Patients and Methods Top


This is a cross-sectional study, in which we compared the levels of serum IGF-1 in 4 groups of children as follows: Group 1: 22 children with CKD stage 5 on regular hemodialysis (HD).

Group 2: 26 children with CKD stages 3 and 4 (glomerular filtration rate (GFR): 15-60 ml/min/1.73m 2 ).

Group 3: 23 children with normal growth. Group 4: 23 children with constitutionally short stature.

The medical charts of the patients in group 1 were reviewed and physical examinations were performed. The recorded data included age, sex, weight and height percentiles, primary renal disease, duration of HD and GFR. Clinical data of the children in group 2 were recorded from their last referral to the pediatric nephrology clinic. The Shwartz formula (GFR ml/min/1.73m 2 = K×length (cm)/serum Cr) was used for determination of GFR.

The third group included age and sex­matched children referred for routine check-up to our outpatient clinics and the 4th group were children with constitutional growth retardation referred to the pediatric endocrinology clinic.

Fasting blood samples were obtained for serum IGF-1 and creatinine (Cr) levels from all the study groups. Before blood sampling, a written informed consent was obtained from the children's parents.

After blood samples were obtained, the serum was separated and frozen and stored at - 10 o C. Serum IGF-1 levels were determined in the endocrinology research laboratory of the Shiraz University Medical Sciences using IGF-1 IRMA kits (Immunotech, France and immuno IRMA method).


   Statistical analysis Top


We used the SPSS software package for the statistical analysis. Comparison of IGF­1 levels in different groups was performed using ANOVA and T-test; a P<0.05 was considered significant.


   Results Top


The primary renal diseases of groups 1 and 2 are summarized in [Table - 1]. The demographic features of study groups and their IGF-1 levels are depicted in [Table - 2].

The differences in IGF-1 levels between groups 1 and 2 and between groups 3 and 4 were not statistically significant. However, IGF-1 levels in groups 1 and 2 were signi­ficantly lower than those in children from the normal GFR group 3 ( P<0.0001), and group 4 (P<0.02 and P<0.004 respectively).

However, the IGF-1 levels were not statistically different among the children with GFRs>30 ml/min/1.73 m 2 and GFRs<30 ml/min/1.73 m 2 in group 2. Furthermore, the difference of the IGF-1 levels between the children with height and weight below and above the 5th percentile in the groups 1 and 2 was not significant.


   Discussion Top


IGF-1 levels have been reported as high, normal, near normal or low in children with CKD and ESRD. [7],[8],[10],[13],[14],[15] Considering the increased growth hormone levels in these children, even the normal IGF-1 levels can be regarded as disproportionately low.[10],[13]

In our study, we found significantly lower IGF-1 levels in our HD children as well as in children with CKD on conservative therapy, as compared to their age-matched normal controls, and children with normal GFR and short stature. The results of our study were similar to those reported by others.[10],[11],[16],[17]

Normal serum IGF-1 levels and mildly increased IGF-II levels should cause normal somatomedin activity, but this is not the case in children with CKD since they have low somatomedin activity. This may be due to increased levels of IGFBP due to decreased renal clearance. IGFBP levels have a negative correlation with the level of GFR.[5],[9],[10]

Similar to other studies, we did not find any correlation between IGF-1 levels and GFR and/or height above or below the 5th percentile in the CKD and HD groups.[11],[16],[18]

Growth hormone therapy has been more effective in children with CKD on conservative therapy than in children with ESRD on maintenance dialysis.[2],[14] Fouque et al [7] found no difference in the pharmoco­kinetics of IGF-1 in children on HD and normal children after subcutaneous injections of 50 µg/kg of IGF-1.

We conclude that we have demonstrated low IGF-1 levels in children at different stages of CKD in comparison to their age­matched controls. Growth hormone therapy may be beneficial if started in the early stages of chronic kidney disease.


   Acknowledgments Top


The authors would like to thank the vice chancellor for research at Shiraz University of Medical Sciences for his support.

 
   References Top

1.Nev AM, Ho PL, McDonald RA, Warady BA. Chronic dialysis in children and adolescents. The 2001 NAPRTCS annual report. Pediatr Nephrol 2002;17:656-63.  Back to cited text no. 1    
2.Pasqualini T, Ferraris JR. Chronic renal insufficiency and growth. Medicina (B Aires) 2003;63(6):731-6.  Back to cited text no. 2    
3.Hokken-Koelega AC, Hackeng WH, stijnen T, Wit JM, de Muinck Keizer-Schrama SM, Drop SL. Twenty-four hour plasma growth hormone (GH) profiles, urinary GH excretion, and plasma insulin-like growth factor-I and-II levels in prepubertal children with chronic renal insufficiency and severe growth retardation.J Clin Endocrinol Metab1990;71:688-95.  Back to cited text no. 3  [PUBMED]  
4.Hodson EM, Brown AS, Roy LP, Rosenberg AR. Insulin-like growth factor­1, growth hormone dependent insulin-like growth factor-binding protein and growth in children with chronic renal failure. Pediatr Nephrol 1992;6:433-8.  Back to cited text no. 4  [PUBMED]  
5.Blum WF, Ranke MB, Kietzmann K, Tonshoff B, Mehls O. Growth hormone resistance and inhibition of somatomedin activity by excess of insulin-like growth factor binding protein in uraemia. Pediatr Nephrol 1991;5:539-44.  Back to cited text no. 5  [PUBMED]  
6.Mehls O, Tonshoff B, Blum WF, Heinrich U, Seidel C. Growth hormone and insulin like growth factor 1 in chronic renal failure­pathophysiology and rationale for growth hormone treatment. Acta Paediatr Scand Suppl 1990;370:S28-34.  Back to cited text no. 6    
7.Fouque D, Peng SC, Kopple JD. Pharmacokinetics of recombinant human insulin-like growth factor-I in dialysis patients. Kidney int 1995;47:869-75.  Back to cited text no. 7  [PUBMED]  
8.Powell DR. Effects of renal failure on the growth hormone-insulin-like growth factor axis. J Pediatr1997;131: S13-6  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Lee PD, Hintz RL, Sperry JB, Baxter RC, Powell DR. IGF binding proteins in growth retarded children with chronic renal failure. Pediatr Res 1989;26:308-15.  Back to cited text no. 9  [PUBMED]  
10.Tonshoff B, Blum WF, Mehls O. Serum insulin-like growth factors and their binding protein in children with end stage renal disease. Pediatr Nephrol 1996;10:269-74.  Back to cited text no. 10  [PUBMED]  
11.Tonshoff B, Blum WF, Aingen AM, Mehls O. Serum insulin-like growth factors (IGF) and IGF binding protein1,2, and 3 in children with chronic renal failure: relationship to height and glomerular filtration rate. J Clin Endocrinol Metab 1995;80:2684-91.  Back to cited text no. 11    
12.Tonshoff B, Kiepe D, Ciarmatori S. Growth hormone/insulin-like growth factor system in children with chronic renal failure. Pediatr Nephrol 2005;20:279-89.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]
13.Houang M, Cabrol S, Perin L, Ducos B, Bensman A, Le Bouc Y. Insulin-like growth factor-I (IGF-I), insulin-like growth factor binding proteins (IGFBP) and insulin-like growth factor type I receptor in children with various status of chronic renal failure. Growth Horm IGF Res 2000;10:332-41.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]
14.Kari JA, Rees L.Growth hormone for children with chronic renal failure and on dialysis. Pediatr Nephrol 2005;20:618-21.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]
15.Cabrol S, Houang M, Le Bouc Y. Physiopathology of the somatotropin axis in chronic renal insufficiency. Arch Pediatr 1998;5 Suppl 4:348s-53s.  Back to cited text no. 15  [PUBMED]  
16.Powell DR, Liu F, Baker BK, et al. Effect of chronic renal failure and growth hormone therapy on the insulin like growth factors and their binding proteins. Pediatr Nephrol 2000;14:579-83.  Back to cited text no. 16  [PUBMED]  [FULLTEXT]
17.Powell DR. Effects of renal failure on the growth hormone-insulin like growth factor axis. J Pediatr 1997;131:S13-6.  Back to cited text no. 17  [PUBMED]  [FULLTEXT]
18.Powell DR, Liu F, Baker BK, et al. Modulation of growth factors by growth hormone in children with chronic renal failure. The Southwest Pediatric Nephrology Study Group. Kidney Int 1997;51:1970-9.  Back to cited text no. 18    

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Correspondence Address:
A Derakhshan
Associate professor of pediatrics, Shiraz University of Medical Sciences, 71937-Pediatric Office, Nemazee Hospital, Shiraz
Iran
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PMID: 17496390

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    Abstract
    Introduction
    Patients and Methods
    Statistical analysis
    Results
    Discussion
    Acknowledgments
    References
    Article Tables
 

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