A comparative analysis of treatment responses across three etiologies of short stature

While recombinant human growth hormone (rhGH) therapy improves growth velocity in pediatric patients with chronic kidney disease (CKD), a comparative analysis across different etiologies of short stature may further elucidate variations in the insulin-like growth factor (IGF) axis response.

This prospective observational cohort study included 86 children with short stature (height SDS < -2): 15 with stage 3-5 CKD, 20 born small for gestational age (SGA), and 51 with idiopathic growth hormone deficiency (IGHD). All patients received rhGH therapy (0.05 mg/kg/day) for 12 months with standardized monitoring every 3 months. The primary outcomes were height velocity and height SDS.

All three groups exhibited significant improvements in height velocity after 12 months of rhGH therapy (CKD: 3.73 to 8.74 cm/year, p<0.001; SGA: 4.07 to 7.78 cm/year, p<0.001; IGHD: 3.55 to 8.06 cm/year, p<0.001). Group comparisons revealed no significant differences in height SDS gains (ANCOVA, p=0.700). CKD patients showed no significant change in insulin-like growth factor 1 (IGF-1) SDS (median change +1.83, p=0.173) despite significant improvements in growth, whereas the SGA (median change +2.24, p=0.002) and IGHD (median change +2.31, p<0.001) groups demonstrated significant increases in IGF-1 SDS. The between-group comparison of IGF-1 SDS change was not statistically significant (p=0.240). Changes in insulin-like growth factor binding protein 3 (IGFBP-3) SDS were statistically significant in the CKD group (median change +2.73, p=0.017), but not in the SGA group (median change +0.50, p=0.054) or the IGHD group (median change +0.45, p=0.180). The between-group comparison of IGFBP-3 SDS change was not statistically significant (p=0.362).

This study reaffirms that recombinant human growth hormone (rhGH) therapy is an effective treatment for growth failure in pediatric patients with chronic kidney disease (CKD) and those born small for gestational age (SGA). The decoupling of total circulating insulin-like growth factor-1 (IGF-1) from growth outcomes in patients with CKD highlights the role of growth hormone (GH) resistance-driven primarily by reduced bioavailability of free IGF-1 rather than absolute total IGF-1 levels-and underscores that total circulating IGF-1 alone is an insufficient surrogate for treatment efficacy in this population. Growth parameters-height velocity and height SDS-should remain the primary endpoints for monitoring rhGH response in children with CKD.