[Serum osteocalcin in children with chronic renal insufficiency]. / Osteokalcin u serumu kod dece s hronicnom insuficijencijom bubrega.

UNLABELLED: The research of the bone metabolism has undergone a long evolution which began with the use of radioisotopes in calcium kinetic studies and went through the determination of several humoral parameters like alkaline phosphatase (ALP), hydroxyproline and intact immunoreactive parathyroid hormone (iPTH) and finally to the assay of a new serum and urinary parameters of bone metabolism, like osteocalcine (OC) and procollagen and collagen metabolites. The X-ray study of the skeleton, densitometric techniques, computerized tomography, scintigraphy and NMR are used for visualization of bone changes, but bone biopsy and histomorphometry provide the most precise evaluation [1]. Disorders of bone and mineral metabolism in children with chronic renal failure (CRF) are an almost regular occurrence; so early discovery and treatment of these changes are very important [2]. The aim of this study was to measure the serum OC level in children with CRF and terminal renal failure (TRF), treated with chronic haemodialysis, and to evaluate the significance of OC compared to other humoral parameters of renal osteodistrophy, such as ALP and iPTH. MATERIALS AND METHODS: We studied the fasting levels of OC in three different groups of children: group A consisted of 18 patients with TRF; group B consisted of 12 patients at different stages of CRF, and group C consisted of 32 healthy children, all of the approximately same age. Clinical characteristics of the examinded children are presented in Table 1. Of 30 patients, 26 were treated with calcium carbonate and 21 with vitamin D analogues. None were treated with aluminium hydroxide. Additional parameters included serum calcium, phosphate, ALP and body height, while serum concentrations of iPTH and ionized serum calcium were measured only in group A. Serum OC was measured by radioimmunoassay using OSTK PR RIA (CIS), while ELISA-PTH (CIS) radioimmunoassay was used to determine iPTH plasma levels. Statistical analyses were performed using Kolmogorov-Smirnov test to confirm normal distribution, the Pearson and Spearman rank sum test for correlation between variables of interest, while analysis of variance was used to compare the findings. RESULTS: Serum OC levels were significantly different in all groups (p < 0.01); they were three times higher in group A than in group C. Similar increase was noticed in plasma iPTH, assuming that "normal" uremic iPTH was raised up to threefold above normal range (between 10 and 60 pg/ml) [2]. However, the total serum ALP activity was not sensitive as OC and iPTH, since ALP increases were less as compared to them. OC was age related only in group A (p < 0.01), with a positive correlation between OC and duration of haemodialysis (p < 0.05), as well as between OC and serum phosphate (p < 0.05), but there was no correlation between OC and growth retardation (expressed by SDS), bone age and current therapy for renal osteodistrophy. A direct correlation between OC and ALP was found only in healthy children (p < 0.01), while in groups A and B it was remarkable, although not statistically significant (p = 0.08) (Graphs 1, 2, 3). In group A, ALP and iPTH were directly correlated (p < 0.001), but the correlation of OC with iPTH was less significant (p = 0.06). In patients with CRF no correlation was found between glomerular filtration rate and OC. DISCUSSION: OC is a bone-derived noncollagenous protein of low molecular weight (about 5800 D), containing residues of the vitamin K dependent amino acid gamma-carboxyglutamic acid and is synthesized by osteoblasts and odontoblasts. Calcitriol is a potent stimulator of OC synthesis, acting at the transcriptional level and increasing mRNA severalfold. OC is found mainly in bone, but nanomolar concentrations circulate in the blood. Its serum levels are an expression of the bone formation process and are age related (higher in the neonatal and adolescent period). ABSTRACT TRUNCATED.

Endothelin-1 in acute renal failure.

To study the pathological significance of circulating endothelin (ET) in ARF, we measured plasma ET in seven children (mean age 8.8 +/- 4.4 years) with ARF in the most severe phase and 3.7 +/- 3.5 months later in the recovery period. Twenty-seven healthy children were included in the study as controls. Plasma ET level was measured by highly sensitive and specific radioimmunoassay for ET-1 and ET-2 (ET-1/2, Biomedica, Vienna). Plasma ET was significantly higher in the most severe phase of ARF (4.75 +/- 4.08 fM/ml) than in the recovery period (0.78 +/- 0.24 fM/ml; p < 0.01), but comparing to plasma ET in the healthy children, the difference was only of borderline statistical significance (Pf, 0.0573). Since plasma concentrations of creatinine did not correlate with plasma ET in patients, either in acute or in the recovery phase of disease, we concluded that decreased GFR is not the main factor determining an increased ET in ARF. We suggest that elevated plasma ET in ARF may be secondary to vascular endothelial dysfunction and speculate that enhancement synthesis of endothelial relaxing factor (EDRF) inhibits ET synthesis during the recovery period. We did not find any relationship between plasma ET and blood pressure (BP) in patients with ARF, so we conclude that circulating ET is not the main factor determining BP in ARF.

[Significance of endothelin in arterial hypertension in children]. / Znacaj endotelina u arterijskoj hipertenziji kod dece.

UNLABELLED: Concentration of plasma endothelin and the activity of Na(+)-K(+)-ATP-ase were determined in 3 different groups of children: the 1st group comprised 13 children with essential hypertension, aged 12.9+/-4.8; the 2nd group concerned 16 children with renal hypertension, but with preserved global renal function, aged 13.7+/-2.8, and the 3rd group consisted of 27 healthy children, aged 11.6+/-6.3 years. Plasma endothelin concentrations were measured by radioimmunological method, using a set manufactured by "Biomedica". The activity of Na(+)-K(+)-ATPase was determined in erythrocyte haemolysate by measuring the quantity of released inorganic phosphate in samples with and without ouabaine. Concentration of plasma endothelin was not significantly different between the children with arterial hypertension and healthy children, and there was no significant correlation between endothelin concentration and blood pressure in either of the 3 groups of children. The activity of Na(+)-K(+)-ATP-ase was significantly decreased only in the 1st group of children. There was no evidence of correlation between the Na(+)-K(+)-ATPase activity and blood pressure or plasma endothelin either in healthy, or in hypertensive children. CONCLUSION: Endothelin in blood circulation has no significance in regulating blood pressure in healthy children. It also has no direct role on the development of essential and renal hypertension in children. The activity of Na(+)-K(+)-ATP-ase is decreased in children with essential hypertension, but it seems that it has no direct impact on hypertension. Endothelin in circulation and Na(+)-K(+)-ATP-ase activity are not interdependant.