Renal function in Laron syndrome patients treated by insulin-like growth factor-I

Eight children with Laron syndrome (5 males, 3 females) aged 3–14.5 years received daily subcutaneous injections of 150 g/kg recombinant insulin-like growth factor-I (IGF-I) for 5 months. The children were examined weekly for the 1st month and then once monthly. At each visit, overnight fasting blood was drawn for serum IGF-I and blood chemistry measurements and a 24-h urine collection was performed for the determination of calcium, phosphorus, creatinine and nitrogen. The main effects related to kidney function were: an initial weight gain with a mild transitory reduction in the urinary volume, an increase in serum electrolyte concentrations and a decrease in urinary electrolyte excretion. The lower than normal mean (± SEM) basal creatinine clearance (76.7±15.8 ml/min per 1.73 m²) increased towards the normal range during treatment to 124.9±13 ml/min per 1.73 m², with a mean increment of 73.4±28% (P<0.02) from basal values after 2 months of treatment, without changes in the serum creatinine. Initially an increase in blood urea nitrogen was observed together with a reduction in urinary nitrogen excretion. During the IGF-I therapy the urinary calcium excretion increased from 0.7±0.2 nmol/day to 1.5±0.3 nmol/day and the tubular reabsorption of phosphate increased from 1.24±0.06 to more than 1.38±0.04 nmol/l (P<0.002), resulting in a significant increase in serum phosphate levels from 1.51±0.06 to more than 1.63±0.04 nmol/l (P<0.005). The present study shows for the first time that long-term IGF-I deficiency in man results in a subnormal glomerular filtration rate and that chronic substitution therapy with IGF-I has marked renotropic effects identical to those ascribed to growth hormone.