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Renal handling of phosphate can predict height velocity during growth hormone therapy for short children
S Nishiyama1, M Ikuta, T Nakamura
1Department of Pediatrics, Kumamoto University Medical School, Japan.
Insights
Growth hormone (GH) therapy significantly improved renal phosphate reabsorption in children with classical GH deficiency. The delta Tmp/GFR/delta IGF-I ratio effectively predicts treatment outcomes in short children receiving GH therapy.
Area of Science:
- Pediatric Endocrinology
- Renal Physiology
Background:
- Children with short stature often exhibit deficiencies in growth hormone (GH).
- Renal tubular phosphate reabsorption is a key factor in phosphate homeostasis and bone metabolism.
- The impact of GH on renal phosphate handling in different types of GH deficiency is not fully elucidated.
Purpose of the Study:
- To investigate the effect of GH administration on renal tubular phosphate reabsorption in short children with varying degrees of GH deficiency.
- To evaluate the relationship between GH, insulin-like growth factor-I (IGF-I), and renal phosphate reabsorption.
- To determine if a specific ratio can predict the therapeutic response to GH treatment.
Main Methods:
- Study included 28 short Japanese children (5-11 years) categorized into classical GH deficiency (n=12), partial GH deficiency (n=7), and non-GH deficiency (n=9).
- GH was administered (0.1 U/kg/day for 4 days) and parameters including serum phosphorus, alkaline phosphatase, IGF-I, osteocalcin, and maximum tubular reabsorption rate for phosphorus to glomerular filtration rate (Tmp/GFR) were measured.
- Long-term GH treatment (0.5 U/kg/week for 1 year) was assessed for height velocity, and the ratio of increment in Tmp/GFR to increment in IGF-I (delta Tmp/GFR/delta IGF-I) was correlated with height velocity changes.
Main Results:
- Children with classical GH deficiency had significantly lower baseline serum phosphorus, Tmp/GFR, and IGF-I compared to other groups.
- Acute GH administration led to significantly greater increments in serum phosphorus and Tmp/GFR in the classical GH deficiency group compared to the partial deficiency and non-deficiency groups.
- The delta Tmp/GFR/delta IGF-I ratio was highest in classical GH deficiency, intermediate in partial deficiency, and lowest in non-deficiency, showing a strong positive correlation with 1-year height velocity increase.
Conclusions:
- GH administration effectively enhances renal tubular phosphate reabsorption in children with classical GH deficiency.
- The delta Tmp/GFR/delta IGF-I ratio serves as a valuable predictive marker for assessing the efficacy of long-term GH therapy in short children.
- This study highlights the crucial role of GH in phosphate metabolism and provides a tool for optimizing GH treatment strategies.
Abstract:
Renal tubular reabsorption of phosphate in response to GH administration was studied in 28 short Japanese children, aged 5-11 yr (height SD score, less than -2.0 SD). Three groups included a classical GH deficiency (group 1; n = 12), a partial GH deficiency (group 2; n = 7), and children with non-GH deficiency (group 3; n = 9), depending on the peak response of serum GH in four provocative tests. Serum phosphorus, alkaline phosphatase, insulin-like growth factor-I (IGF-I), osteocalcin, and ratio of the maximum tubular reabsorption rate for phosphorus to the glomerular filtration rate (Tmp/GFR) were all significantly lower in group 1 compared with findings in groups 2 and 3 (P less than 0.05, P less than 0.01, and P less than 0.001). After the administration of GH (0.1 U/kg.day) for 4 consecutive days, increments in serum phosphorus and Tmp/GFR were significantly higher in group 1 than in group 2 (P less than 0.01 and P less than 0.01) or group 3 (P less than 0.01 and P less than 0.01), whereas the increment in IGF-I was similar in all 3 groups, and the levels of serum alkaline phosphatase and osteocalcin remained unchanged in all 3 groups. The calculated ratio of the increment in Tmp/GFR to the increment in IGF-I (delta Tmp/GFR/delta IGF-I) was highest in group 1, intermediate in group 2, and lowest in group 3 (P less than 0.001). One year after the GH treatment (0.5 U/kg.week), height velocity was 7.9 +/- 2.2 cm/yr in group 1 and 5.9 +/- 1.2 cm/yr in group 2; no child in group 3 was treated. When the above calculated parameters, delta Tmp/GFR/delta IGF-I and increment in height velocity (difference between pre- and posttherapy values), were taken into account, there was a significant positive correlation (n = 19; r = 0.78; P less than 0.001). This parameter can be used for purposes of predicting the outcome after 1 yr of GH therapy.