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  • 1
    ISSN: 1432-1076
    Keywords: Chronic renal failure ; Recombinant human growth hormone treatment ; Insulin-like growth factors ; Insulin-like growth factor binding proteins ; Progression of renal disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Impaired growth and stunting remains a major therapeutic problem in children with chronic renal failure (CRF). Recombinant human growth hormone (rhGH) treatment may be beneficial, but concern has been raised about possible side-effects, i.e. deterioration of renal function and glucose intolerance. We have treated 10 prepubertal children with CRF (median age 7.5 [1.7–10.0] years) with 4 IU rhGH/m2 per day s.c. over a period of 1 year. Height velocity increased significantly (P〈0.03) from basal 4.6 (2.0–14.0) cm/year to 9.7 (6.8–17.6) cm/year. Height velocity SDS for chronological age and for bone age increased in all children from basal median −2.3 to +3.8 (P〈0.005). Median glomerular filtration rate (GFR) measured by single injection inulin clearance at onset was 18 (11–66) ml/min per 1.73 m2 and did not change significantly during the treatment year. The loss of GFR as estimated by creatinine clearance was similar during the treatment year (median loss 1.3 ml/min per 1.73 m2) compared to the year before treatment (median loss 3.7 ml/min per 1.73 m2). Serum glucose levels during an oral glucose tolerance test did not change, but fasting as well as stimulated insulin levels increased significantly with time during the study period. It is concluded that the rhGH regimen employed was remarkably effective in improving growth velocity in children with CRF without adversely affecting GFR. Glucose homeostasis remained stable, but at the expense of increased serum insulin levels.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-198X
    Keywords: Key words Chronic renal failure ; Insulin-like growth factors ; Insulin-like growth factor binding proteins ; Growth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Growth retardation in children with chronic renal failure (CRF) is partly due to an inhibition of insulin-like growth factor (IGF) activity by an excess of high-affinity IGF-binding proteins (IGFBPs). The aim of this study was to analyze the serum levels and forms of IGFBP-4 and IGFBP-5 in CRF patients using specific, recently developed radioimmunoassays (RIAs) and immunoblot analysis. We examined 89 children [age 11.5 (2.8–19.0) years] with CRF [glomerular filtration rate 26.6 (7.0–67.4) ml/min per 1.73 m2], nine of them with end-stage renal disease undergoing peritoneal dialysis. Serum-immunoreactive IGFBP-4 levels were fourfold increased in CRF (prepubertal 1080±268 ng/ml; pubertal 989±299 ng/ml) compared to healthy prepubertal controls (265±73 ng/ml). In contrast, serum IGFBP-5 levels were not significantly increased neither in prepubertal (361±120 ng/ml vs 282±75 ng/ml in controls) nor pubertal CRF children (478±165 ng/ml vs 491±80 ng/ml in controls). Immunoblot analysis showed the presence of intact as well as fragmented IGFBP-4 and IGFBP-5. Serum IGFBP-4, but not IGFBP-5, levels were inversely correlated with GFR (r=–0.39, P〈0.001). In prepuber- tal children, IGFBP-4 levels were inversely correlated with standardized height (r=–0.40; P〈0.005). In contrast, IGFBP-5 levels were positively correlated both with standardized height (r=0.32, P〈0.02) and baseline height velocity (r=0.45, P〈0.005). A 3-month therapy with rhGH stimulated serum IGFBP-5 levels by 43% (P〈0.01); there was no consistent effect on IGFBP-4 levels. There was a positive correlation between IGFBP-4 and IGFBP-2 (r=0.46, P〈0.001); IGFBP-5 was positively correlated with IGF-I (r=0.59, P〈0.001), IGF-II (r=0.42, P〈0.001) and IGFBP-3 (r=0.47, P〈0.001) and inversely correlated with IGFBP-1 (r=–0.41, P〈0.001). In summary, serum IGFBP-4 is fourfold elevated in children with CRF in relation to the degree of renal dysfunction and contributes to the marked increase in IGF-binding capacity in CRF serum. The inverse correlation of serum IGFBP-4 with standardized height is consistent with its role as another inhibitor of the biological action of the IGFs on growth plate cartilage. In contrast, serum IGFBP-5 is not elevated in CRF serum and circulates mainly as proteolysed fragments. The positive correlation of serum IGFBP-5 with growth and its increase during GH therapy indicate that IGFBP-5 is a stimulatory IGFBP in patients with CRF, either by enhancing IGF activity through better presentation of IGF to its receptor or by an IGF-independent effect through activation of a specific, recently described putative IGFBP-5-receptor.
    Type of Medium: Electronic Resource
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