The impact of recombinant human growth hormone (rhGH) treatment on growth, bone mineral metabolism, and bone mineral density (BMD) was evaluated in six children (3 girls, 3 boys) with familial hypophosphatemic rickets (XLH). Five were prepubertal (aged 6-8.8 years), one 15.3-year-old boy had combined XLH and GH deficiency, but had not been treated with rhGH previously. rhGH was administered daily for 1 year, at a dose of 1 IU/kg per week, combined with 1,25-dihydroxyvitamin D3 and oral phosphate therapy. Z scores for growth velocity and height improved significantly (-2.9 vs. 2.5, P < 0.01, and -2.2 vs. -1.5, P < 0.01, respectively). However, the ratio of Z score for height to that of subischial leg length decreased significantly (0.65 vs. 0.43, P < 0.01), indicating disproportionate growth in favor of the trunk. The height-corrected BMD Z increased slightly (-0.99 vs. -0.94, P < 0.05). A slight increase in serum phosphate occurred (0.78 vs. 0.88 mmol/l, P < 0.02). Tubular reabsorption of phosphate/glomerular filtration rate increased from 0.45 mmol/l to 0.55 mmol at 6 months (P < 0.02), but returned to the initial level at 12 months. These results indicate that children with XLH can benefit from the positive effect of rhGH on growth, however treatment could aggravate the already existing tendency to disproportionate growth. GH production should be evaluated in poorly growing patients with XLH, because it can mask GH deficiency. rhGH can be safely combined with conventional treatment in XLH. Further studies are needed to determine the effect of treatment on final height and maximal BMD.

Hemodialysis (HD) causes rapid volume shifts and circulatory changes. In chronic renal failure (CRF) Na+/K+ATP-ase is depressed, whereas endogenous digoxin-like factor (EDLF) is elevated. Our aim was to characterize HD-induced cardiovascular adaptation and its possible links to Na+/K+ATP-ase and EDLF. Eleven children with CRF on HD (aged 14.7 +/- 3.7 years) and 11 healthy children were investigated for basic circulatory parameters. Thoracic impedance (Zo) and circulatory parameters were monitored by impedance cardiography (ICG) during HD. Erythrocyte Na+/K+ATP-ase and EDLF were measured before and after HD. Up to the loss of 6% of total body weight, Zo rose linearly with fluid removal, above this no further increase occurred. Heart rate and mean arterial pressure (MAP) were inversely related (r = -0.97); MAP rose in the first and decreased in the second part of HD. Systemic vascular resistance paralleled MAP, whereas stroke volume rapidly decreased, but stabilized in the second part of HD. The ratio of preejection period/ventricular ejection time (PEP/VET) correlated positively with HD duration (r = 0.92), suggesting diminished cardiac filling. Cardiac index (CI) remained stable. EDLF was high in uremia accompanied by depressed Na+/K+ATP-ase (P < 0.05 and P < 0.01, respectively). Following HD Na+/K+ATP-ase normalized. Correlation between Na+/K+ATP-ase activity and MAP was linear (r = 0.85). In conclusion, ICG during HD provides detailed information concerning circulatory adaptation resulting in stable CI, suggesting that the dialysis-induced hypovolemia is compensated by the centralization of the blood volume. Changes of Na+/K+ATP-ase indicate that dialyzable blood pressure-regulating substance(s) inhibit(s) the pump. However, lack of further correlation between Na+/K+ATP-ase, EDLF, and cardiovascular parameters indicates the complexity of the regulatory processes.

The mechanisms of sodium retention in edema-forming minimal change nephrotic syndrome (MCNS) have not been completely evaluated. The aim of this study was to characterize the transmembrane sodium transport in nephrotic syndrome by measuring the erythrocyte sodium-lithium countertransport (SLC) in vitro. Eighteen children with MCNS were studied in the edema-forming state, and subsequently at the beginning of remission. Nephrotic children with edema retained sodium (10+/-12 micromol/day) and had a higher SLC [426+/-118 vs. 281+/-60 micromol/l red blood cells (RBC) per hour, P=0.003). The intracellular sodium concentration of nephrotics was 6.1+/-2.1 mmol/l RBC, which did not differ from that of controls (6.42+/-2.24, n=13). In remission sodium balance became negative (-30+/-21 mmol/day), and the SLC decreased but still differed significantly from control values (P=0.009). The intracellular sodium content decreased to 4.4+/-0.9 mmol/l RBC (P=0.002). There was a negative correlation between erythrocyte SLC and plasma albumin concentration (r=0.48, P=0.003), and urinary sodium excretion rate (r=0.66, P=0.001). In conclusion, erythrocyte SLC is high in the edema-forming state of childhood nephrotic syndrome and decreases with the onset of remission. A role for the SLC in the altered sodium homeostasis of nephrotic syndrome is suggested.