| 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|| |
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).,
Growth hormone stimulates production and release of IGF-1 as well as inducing direct effects on target tissues.,,,
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.,
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.,,,,
Previous studies revealed variable levels of IGF-1 in children with CKD.,
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|| |
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|| |
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|| |
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|| |
IGF-1 levels have been reported as high, normal, near normal or low in children with CKD and ESRD. ,,,,, Considering the increased growth hormone levels in these children, even the normal IGF-1 levels can be regarded as disproportionately low.,
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.,,,
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.,,
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.,,
Growth hormone therapy has been more effective in children with CKD on conservative therapy than in children with ESRD on maintenance dialysis., Fouque et al  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|| |
The authors would like to thank the vice chancellor for research at Shiraz University of Medical Sciences for his support.
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Associate professor of pediatrics, Shiraz University of Medical Sciences, 71937-Pediatric Office, Nemazee Hospital, Shiraz
[Table - 1], [Table - 2]