Effect of dialysis dose on nutritional status of children on chronic hemodialysis.

It had been suggested that larger hemodialysis (HD) doses in children could result in better appetite, higher protein intake, better nutritional status and better growth. We investigated how different HD doses affect protein intake and nutritional status of children on chronic HD. Indices of nutritional status used were normalized protein catabolic rate (nPCR) calculated by formal 3-sample urea kinetic modeling and serum albumin level. Data of 38 HD sessions in 15 stable patients (6 males, 9 females) aged 14.5 +/- 3.28 years (mean +/- SD) were analyzed. HD sessions were divided into three groups based on delivered Kt/V: group 1 (n = 5), inadequate (Kt/V < 1.3, mean 1.05 +/- 0.14); group 2 (n = 12), adequate (Kt/V = 1.3-1.6, mean 1.50 +/- 0.07) and group 3 (n = 21), high (Kt/V >1.6, mean 1.94 +/- 0.22). Mean nPCR and Kt/V per patient during the studied week were estimated for 11 patients in whom 3 HD sessions were available within the 38 sessions analyzed. Serum albumin level was adequate in all patients (43.77 +/- 2.28 g/l). Mean overall Kt/V and nPCR were 1.68 +/- 0.36 and 1.26 +/- 0.23, respectively, r = 0.430. Average nPCR differed between groups depending on Kt/V. It was lowest in group 1 (1.01 +/- 0.12 g/kg/day) where the highest correlation between nPCR and Kt/V was found (r = 0.648). nPCR was higher and similar in groups 2 (1.27 +/- 0.23 g/kg/day) and 3 (1.31 +/- 0.22 g/kg/day), with low correlation coefficients between nPCR and Kt/V in both groups (r = 0.275 and r = 0.197, respectively). A weak positive correlation (r = 0.249) between nPCR and Kt/V was found when average weekly values per patient (n = 11) were analyzed. Results of groups 1 and 2 confirm, what is already well established in adults, that adequate dialysis needs to be achieved in order to insure good protein intake. However, our data clearly show that nPCR did not increase with a further increase in delivered HD dose, i.e. Kt/V >1.6. Our results show that the nutritional status of children on chronic HD does not seem to benefit from very high HD doses (Kt/V >1.6).

[The Lesch-Nyhan syndrome]. / Les-Nijanov (Lesch-Nyhan) sindrom.

Deficiency of hypoxanthine phosphoribosyltransferase (HPRT) has a broad spectrum of clinical manifestations, from the complete enzyme defect, the Lesch-Nyhan syndrome with severe neurological deficiency to the partial defect associated only with uric acid overproduction and its consequences. We present a 5-year old boy with Lesch-Nyhan syndrome. He came to our hospital because of abdominal pain, vomiting and gross haematuria. At the age of 8 months he was categorized as a "cerebral palsy" patient due to involuntary movements and high degree of spastically and tonic spasms. He remained incapable of sitting or standing alone. The patient's brother and two uncles were also categorized as "cerebral palsy" cases and died at the age of 8-14 years. Clinical examination revealed hyperuricaemia and hyperuricosuria, radiolucent renal and urinary bladder stones. HPRT enzyme activity was totally absent, while adenine phosphoribosyl transferase activity was increased compared to control. The patient was treated with allopurinol, urinary alkalization, low-purine diet and adequate hydration while he was in hospital. However, his parents refused further treatment and follow-up. The most important issue is whether the healthy sisters of the patients are heterozygotes for HPRT deficiency. This DNA analysis is now in progress.

[Bartter's syndrome: new classification, old therapy]. / Barterov sindrom: nova podela, stara terapija.

We report on two cases of Bartter's syndrome, together with the review of current literature on the aetiology, development and treatment of Bartter's syndrome. Bartter's syndrome belongs to a group of hypokalaemic renal channelopathies, which are caused by a molecular hereditary disorder of ion channels in renal tubules. These channels are located in the lipid layer of cell membranes where they exist as water channels through which ion transport is performed. Based on the type of genetic disorder and clinical presentation, Bartter's syndrome is classified as neonatal, classical and Gitelman's syndrome. Neonatal form is found in newborns and is characterized by foetal polyuria, premature birth, postnatal episodes of severe dehydration, growth retardation, hypercalciuria and early nephrocalcinosis. It is the result of mutation of a gene responsible for renal tubular Na-K-2Cl cotransport or another gene which controls the ATP-dependant potassium channel (ROMK). Classic form is found in young children with polyuria, hypokalaemia and growth retardation. This type is caused by a defect of a gene for chloride channel (CIC-Kb) in the distal tubule. Gitelman's syndrome is found in late childhood or adolescence. It is caused by mutation in the gene for Na-Cl co-transport in the distal tubule. Children with Gitelman's syndrome occasionally have muscle weakness or tetany, hypokalaemia and hypomagnesaemia. Even though there have been advances in understanding the aetiology and pathogenesis of Bartter's syndrome in the recent years, the possibilities and strategies for its management remained almost the same. Treatment is based on prostaglandin inhibitors, potassium sparing diuretics and substitution therapy.

Prediction of equilibrated urea in children on chronic hemodialysis.

Urea rebound (UR) after hemodialysis (HD) requires the use of equilibrated urea (Ceq) instead of immediate end-dialysis urea (Ct) for correct quantification of HD, which is impractical. A new formula for predicting Ceq in children is suggested in our study. Thirty eight standard pediatric HD sessions (single pool Kt/V = 1.70 +/- 0.35, K = 4.65 +/- 1.14 ml/min/kg, UF coeff. = 3.2-6.2 ml/h/mm Hg, t = 3.80 +/- 0.46 h) in 15 children (M: 6, F: 9), ages 14.5 +/- 3.28 years were analyzed. Blood samples were taken: before, 70 min from the start, at the end, and 60 min after the end of HD sessions. After correlating UR (20.32 +/- 7.74%) to various HD parameters, we found that it was mainly determined by HD efficiency parameters. Therefore we correlated Ceq to HD efficiency parameters (Ct, urea reduction ratio, Kt/V, and K/V) and found a very high correlation between Ct and Ceq (r = 0.973). Linear regression analysis was used to further investigate this relationship, and a new formula to predict Ceq from Ct was obtained (Ceq = 1.085 Ct + 0.729, R2 = 0.946, SE = 0.49, absolute residuals = 0.38 +/- 0.29 mmol/L). In a validation study (10 HD sessions with new set of urea blood samples) the results obtained by the new formula were compared with measured values of Ceq and those obtained by the Smye formulae. Values predicted by the new formula (9.91 +/- 2.92 mmol/L) were not significantly different from the measured values (10.33 +/- 3.44 mmol/L). Absolute error of the new formula was 0.78 +/- 0.73 mmol/L, median 0.65; ie., 6.93 +/- 5.3%, median 7.7%. Ceq predicted by the Smye formulae (10.95 +/- 4.18 mmol/L) also did not significantly differ from the measured values, but absolute error of predicted values was markedly higher (1.21 +/- 0.90 mmol/L, median 0.89; 11.73 +/- 7.72%, median 10.11%; p < 0.05). When predicted Ceq was used for calculating equilibrated Kt/V (eKt/V), the new formula resulted in lower absolute error (0.09 +/- 0.07, median 0.08) than the Smye method (0.14 +/- 0.08, median 0.12). We conclude that our simple formula is sufficiently accurate in predicting Ceq in standard pediatric HD and that it is more accurate than the existing Smye formulae, while requiring only pre- and post-HD urea samples. We suggest the use of the new formula for predicting Ceq, which can then be used instead of Ct for a more accurate estimation of double pool Kt/V, URR, V, and PCR.

Effects of postdialysis urea rebound on the quantification of pediatric hemodialysis.

Urea rebound (UR) causes single pool urea kinetic modeling (UKM), which is based on end-dialysis urea instead of its equilibrated value (Ceq), to erroneously quantify hemodialysis (HD) treatment. We estimated the impact of postdialysis UR on the results of formal variable volume single pool (VVSP) UKM [Kt/V, urea distribution volume (V), urea generation rate (G), normalized protein catabolic rate (nPCR), and urea reduction ratio (URR)] in children on chronic HD. Thirty-eight standard pediatric HD sessions in 15 stable patients (9 female, 6 male) aged 14.5 +/- (SD) 3.28 years were investigated. The HD sessions lasted 3.75 +/- 0.43 h. The single pool urea clearance was 4.84 +/- 1.25 ml/min/kg. All HD sessions were evaluated by VVSP and URR (%) with postdialysis urea taken at the end of HD and with Ceq taken 60 min after the end of HD, incorporating double pool effects and representing true double pool values. The anthropometric V was calculated by Cheek and Mellits formulae for children. VVSP significantly overestimated Kt/V by 0.26 +/- 0.18 U (1.68 +/- 0.36 vs. 1.42 +/- 0.30, p < 0.0001), i.e., 19. 05 +/- 13.07%, G/V (0.20 +/- 0.04 vs. 0.18 +/- 0.04, p < 0.0001), nPCR (1.26 +/- 0.23 vs. 1.18 +/- 0.22 g/kg/day, p < 0.0001), and URR (73.92 +/- 6.49 vs. 69.22 +/- 7.06, p < 0.0001). VVSP significantly underestimated kinetic V in comparison to anthropometric V (18.74 +/- 4.04 vs. 20.76 +/- 4.43 liters or expressed as V/body weight: 58 +/- 8 vs. 65 +/- 9%, p < 0.05), while double pool kinetic V was more accurate (21.45 +/- 4.34 liters, V/body weight: 64 +/- 6%, p > 0.05). We conclude that UR has a significant effect on all results of UKM even after standard pediatric HD, and the degree of this efffect is documented. We suggest an increase of the minimum required prescribed single pool Kt/V in children and reduction of any delivered single pool Kt/V by approxiamtely 0.26 Kt/V U. Overestimation of nPCR by approximately 0.08 g/kg/day and underestimation of V by 8.5% should be kept in mind.

Hyponatremic hypertensive syndrome.

We report on a 4-year-old girl with hyponatremic-hypertensive syndrome (HHS), a rare entity in childhood. The girl was referred to us from a local hospital with a history of recurrent fever, vomiting, and seizures. On admission she was markedly dehydrated. Initial investigations revealed severe hyponatremia (serum Na 120 mmol/l), hypochloremia (serum Cl 68 mmol/l), and mild hypokalemia (serum K 3.3 mmol/l), while serum calcium and magnesium were normal. Serum urea was 5 mmol/l and serum creatinine was 62 mumol/l. Despite hyponatremic dehydration, her urine output was high (2050 ml/24 h), as was her urinary sodium (168 mmol/24 h). She had massive transient proteinuria (maximal 1642 mg/24 h) while being severely hypertensive (blood pressure 210/160 mmHg). Further investigations revealed right kidney scarring, hyper-reflexive bladder dysfunction, massive brain infarcts, and myocardial left ventricular hypertrophy. Renal arteries were normal on arteriography. Blood pressure control resulted in normalization of serum and urinary electrolytes and decrease of proteinuria. Hyponatremia and transient massive proteinuria in this patient seem to be caused by high-pressure-forced diuresis due to malignant renoparenchymal hypertension.

[20 years' experience in the treatment of children with terminal renal insufficiency in Yugoslavia]. / Dvadesetogodisnje iskustvo u lecenju dece s terminalnom insuficijencijom bubrega u Jugoslaviji.

The first specialized haemodialysis (HD) paediatric centre in former Yugoslavia was established at the University Children's Hospital in Belgrade in January 1980. A total of 194 children (F: 98, M: 96), aged less than 19 years (10.12 +/- 4.23), were treated for renal replacement therapy (RRT) over 20 years. Average annual incidence rate was 1.59 per million of child population (pmcp) aged less than 19 years for the period 1980-1990 (former Yugoslavia) and 2.85 pmcp aged less than 19 years for the period 1990-2000 (present Yugoslavia). Reflux nephropathy was the most frequent underlying disease and accounted for 37.06% of total cases, while other primary renal diseases were: glomerulonephritis (GN) 17.26%, cystic/hereditary familial nephropathy 12.69%, congenital disease 11.68%, interstitial nephritis 5.58%, non-recovered tubular necrosis 3.55%, secondary GN 1.52% and 10.66% remained with doubtful diagnosis. HD was the first RRT in 84.02%, peritoneal dialysis (PD) in 14.43% and pre-emptive transplantation in 1.55% of all patients. A total of 53 patients (27.3% of total terminal renal failure (TRF) patients) received 56 kidney transplants (58.93% live related, 37.50% cadaveric, 3.57% live-non related). Actual survival in RRT was 64.53% 5 in years; 51.68% in 10 and 48.23% in 15 years. Patient survival in HD was significantly better over the last ten-year period than in the first ten-year period (35.88% vs. 75.75%; p < 0.005) as well as the survival of transplanted patients in the same two periods (67.62% vs. 95.45%). Graft survival was 79.85% in 5 and 70.50% in 10 years. Cardiovascular complications were the most common cause of death of patients on RRT (56.10 posto) followed by infection (24.39). On December 31, 1999, 54 patients on RRT were alive less than 19 years: 75.92% in HD; 22.22% with functioning graft and 1.85% on automatic PD. This is the first national-wide long-term study of incidence and aetiology of paediatric TRF and outcome of paediatric RRT in Yugoslavia.

Comparison of two methods for predicting equilibrated Kt/V (eKt/V) using true eKt/V value.

Two methods have been suggested by Daugirdas and Schneditz (the rate equation), and Smye for predicting true equilibrated Kt/V (eKt/V) without the need for obtaining a blood sample 60 min after hemodialysis (HD). We compared the accuracy of these two methods when applied to pediatric HD. Thirty-eight standard pediatric HD sessions in 15 patients, (6 male, 9 female), aged 14.5+/-3.3 years, were analyzed. Kt/V was calculated by formal variable-volume single-pool urea kinetic model with post-HD urea taken at the end of HD (single-pool Kt/V), and with equilibrated urea (Ceq) taken 60 min after the end of HD (eKt/V). eKt/V was predicted by the rate equation from single-pool Kt/V and by the Smye method from predicted Ceq. Mean values obtained by both the rate equation (1.44+/-0.32, P>0.05) and by the Smye method (1.47+/-0.36, P>0.05) were similar to eKt/V (1.42+/-0.30), but correlation between results from the rate equation and eKt/V (r=0.863) was higher than between those from the Smye method and eKt/V (r=0.654). Average absolute error of the rate equation in predicting eKt/V was 0.118+/-0.114 (median 0.095) Kt/V units and 8.53%+/-8.36% (median 6.29%), while for the Smye method it was significantly higher [0.221+/-0.180 (median 0.190) Kt/V units, P=0.001; 16.49%+/-15.98% (median 11.88%) P=0.004]. High correlation between eKt/V and results from the rate equation indicates that urea rebound (expressed as delta Kt/V) is a function of the rate of dialysis (K/V). To test this, we analyzed the relationship of K/V and other parameters (session duration, body mass index, ultrafiltration rate, blood flow, and urea distribution volume) with delta Kt/V. The only significant (P<0.01) and highest correlation (r=0.442) was found for K/V. We conclude that in children on chronic HD, the rate equation is a better predictor of eKt/V than the Smye method, and that HD efficiency is the strongest determinant of postdialysis urea rebound in children.

[The captopril test--an aid in the detection of scarring nephropathy as a cause of arterial hypertension in children]. / Kaptoprilski test--pomoc u otkrevanju oziljene nefropatije kao uzroka arterijske hipertenzije kod dece.

Renal scarring with and without vesicoureteral reflux (VUR) has been now recognized as an important cause of paediatric hypertension for many years [1-5]. However, its pathogenesis has still remained uncleared. The widespread concept implicated the activation of renin-angiotensin system finding a powerfull support in higher peripheral plasma renin activity (PRA) in children with reflux nephropathy than in controls [6, 7] and in beneficial antihypertensive effects of ACE inhibitors. The latter, in form of captopril, has also been used in captopril test and in renal scintigraphy and isotope renography following the administration of captopril to provide evidence for renin dependent hypertension [8, 9]. Published studies of captopril test have centred on the identification of renovascular as opposed to essential hypertension [10-18, 20-22]. The aim of our study was to assess the usefulness of captopril test in differentiation between hypertensive children with renal scarring from those with essential hypertension. We studied blood pressure (BP) and PRA responses to a single dose of captopril in two groups of hypertensive children. Group A consisted of 29 patients, 14 boys and 15 girls, who had renal scaring as demonstrated by renal 99mTc dimercaptosuccinid acid scan (99m Tc DMSA) and/or intravenous pyelography. Group B included 19 patients, 19 boys and 10 girls who had arterial hypertension, while clinical examination excluded renal and other definable causes of BP elevation, and they were therefore considered to have essential hypertension. At the time of the study all patients had normal glomerular filtration rate and were not salt depleted. They did not receive any antihypertensive medication for at least two weeks. The test was performed in the morning in fasting sitting patients. At the start of the test a small vein in the hand or forearm was cannulated to permit blood sampling. BP was measured 10, 20, and 30 minutes before captopril administration to get baseline BP (mean of these three measurements) and to allow the children to become accustomed to the test procedure. A single oral dose of captopril 0.64 +/- 0.04 mg/kg body weight was given to patients from group A and almost the same dose of captopril, 0.63 +/- 0.05 mg/kg body weight, to patients from group B. The patients remained sitting and BP was measured every 15 minutes during an hour. Blood for PRA was drown in the sitting position (17 patients from group A and 16 patients from group B) before and one hour after the dose of captopril. Samples of blood for basal PRA were collected from 16 patients from group A and in 14 patients from in B in lying position after waking up in the morning. PRA was measured by radioimmunoassay using a commercially available kit, SB-REN 2, from CIS Bio International. According to the criteria of Muller et al. [10] the captopril test was positive if the post-captopril PRA (ng/ml/h) was greater than or equal to 12 with an increase of greater than or equal to 10 and relative increase of greater than or equal to 15% (400% if initial PRA was < 3). The results of our study are presented in Tables 1 and 2 and in Graphs 1 and 2. The age of patients, doses of captopril, initial BP and PRA before the use of captopril did not much differ between studied groups. Fall of BP and PRA increase were highly significant (p < 0.001) both in group A and group B. However, the hypotensive reaction of diastolic BP and MAP were more pronounced in group A (14.45 +/- 1.67% and 15.81 +/- 1.62%) than in group B (6.95 +/- 2.21% and 8.96 +/- 1.75%; p < 0.01), but there were no significant differences in PRA and systolic BP changes and positive results of captopril test between the studied groups. Hypotensive responses of diastolic BP and MAP greater than 10% of initial values were found to be more frequent in group A (79.32% and 79.31%) than in group B (26.61% and 31.57 degrees %; p < 0.001 and p < 0.01). Diastolic BP and MAP were directly related to the dose of cap

[Renal tubular function in children with hypercalciuria]. / Funkcije tubula bubrega kod dece s hiperkalciurijom.

INTRODUCTION: Renal stone disease is commonly due to hypercalciuria [1, 2], which may be assessed either from a 24-hour urinary collection or from the fasting first morning urine. Hypercalciuria during childhood has been defined by a 24-hour calcium excretion greater than 3.5 mg/kg per day and/or calcium to creatinine ratio greater than 0.20 [3]. The alteration in the calcium transporting systems plays a pathogenetic role in promoting hypercalciuria [4, 5]. Since calcium reabsorption along the nephron is intimately related to that of other electrolytes and substances, it can be hypothesized that patients with hypercalciuria may have other renal tubular defects. The aim of the study was to investigate proximal tubular function (tubular reabsorption of sodium, potassium, phosphate and glucose) and distal tubular function (urinary concentrating capacity and acidifying capacity) in children with hypercalciuria. PATIENTS AND METHODS: Two groups of children were studied: hypercalciuric group included 23 children with hypercalciuria (10 males, aged 11.9 +/- 4.1 years), of whom 6 with nephrolithiasis, and control group included 42 healthy children (20 males, aged 11.2 +/- 3.8 years). All subjects had normal serum values for calcium, sodium, potassium, phosphate and glucose, as well as normal renal function. The urinary excretion of calcium, sodium, potassium, phosphate, glucose and creatinine was measured in a 24-hour urine specimen by standard laboratory methods. Urine osmolality and urinary specific gravity were measured following 12-hour water-deprivation test. A short ammonium chloride loading test was performed in 3 patients with urinary pH above 5.5. The fractional excretion of sodium, tubular phosphate reabsorption and renal threshold phosphate concentration were calculated according to standard formula. Statistical analysis was performed using the t-test and analysis of variance (ANOVA). Kruskal-Wallis method was used to compare urinary phosphate excretion between two groups. RESULTS: Table 1 summarizes urinary excretion of electrolytes in children with hypercalciuria compared with healthy controls. We found that urinary sodium excretion was significantly increased in patients with hypercalciuria when compared with controls (p < 0.05). Urinary phosphate excretion was significantly higher in patients with hypercalciuria in comparison to controls, and this was accompanied by a significant lowering of the tubular phosphate reabsorptive threshold (p < 0.05). Urinary potassium excretion tended to be lower, although not significantly, in the hypercalciuric children than in normal subjects. Table 2 shows the mean values +/- standard deviation of urinary specific gravity, urinary osmolality and urinary pH. Urinary specific gravity mean value was significantly lower in patients with hypercalciuria in comparison to controls (p < 0.05). Urinary pH was found below 5.5 in all patients. Glycosuria was detected in 3 patients (13.3%). As shown in Graph. 1, a significant correlation between the urinary excretion of calcium and sodium was demonstrated in both groups of children (r = 0.29; p < 0.01). DISCUSSION: The present study shows that children with hypercalciuria have significantly higher urinary sodium and urinary phosphate excretion in comparison to controls, while urinary potassium excretion is normal in both groups of children. According to some recent reports [6-9], these findings may indicated defects of the renal tubular transport of sodium and phosphate which may be interpreted as a cause or a consequence of the alteration of the calcium transporting system. Defects in both proximal and distal renal tubular functions have been demonstrated in patients with nephrolithiasis, particularly those with hypercalciuria. Proximal renal tubular defects include defects in sodium, fluid, phosphate and glucose reabsorption, which were evident also in our patients. (ABSTRACT TRUNCATED)

[Sodium excretion in children with lithogenic disorders]. / Izlucivanje natrijuma kod dece s litogenim poremecajima.

INTRODUCTION: The causes of nephrolithisis are multifactorial and have not yet been enough investigated [1]. Hypercalciuria is the most common cause of metabolic nephrolithiasis [2-4]. Close relationship between urinary calcium and urinary sodium has been a subject of reported observations in the past, showing that high urinary sodium is associated with high urinary calcium [5-7]. Hyperoxaluria, hyperuricosuria and cystinuria are also metabolic disorders that can lead to nephrolithiasis. Recent studies have indicated that urinary elimination of cystine is influenced by urinary sodium excretion. Based on these observations it has been hypothesised that patients with high urinary sodium excretion are at high risk of urinary stone disease. The purpose of the study was to investigate sodium excretion in a 24-hour urine and first morning urine collected from children with lithogenic metabolic abnormalities (hypercalciuria, hyperoxaluria, hyperuricosuria, cystinuria), both with nephrolithiasis and without it, in order to determine its significance in urinary calculi formation. PATIENTS AND METHODS: Urinary sodium excretion was investigated in 2 groups of children: patients with lithogenic metabolic abnormalities, but without urinary stone disease (L group) and patients with nephrolithiasis (C group). Both groups were divided into 2 subgroups: patients with hypercalciuria and without it. There were 22 patients in group L (mean age 11.97 +/- 4.13 years), of whom 17 formed a hypercalciuric subgroup and 5 formed a non-hypercalciuric subgroup (3 patients with hyperuricosuria and 2 patients with hyperoxaluria). Group C consisted of 21 patients with nephrolithiasis (mean age 12.67 +/- 3.44 years), of whom 6 formed a hypercalciuric subgroup and 15 formed a non-hypercalciuric group (2 patients with cystinuria and 13 patients without lithogenic metabolic abnormalities). Control group consisted of 42 healthy age-matched children. All subjects had a normal renal function. A detailed history and clinical examination were done, and ultrasonography was performed in all patients. A 24-hour urine, first morning urine and serum specimen were analysed for sodium, potassium, calcium, uric acid, urea and creatinine. Fractional excretion of sodium, as well as urinary sodium to creatinin ratio and urinary sodium to potassium ratio, were calculated from the findings. Sodium and potassium levels were determined by flame photometry, calcium was measured by atomic absorption technique (Beckman Atomic Spectrophotometer, Synchron CX-5 model, USA), uric acid by carbonate method and creatinine by Jaffe technique. Cystine and dibasic amino acids were quantified by ion chromatography. Urinary oxalate excretion was determined by enzyme spectrophotometry. Hypercalciuria was defined by 24-hour calcium excretion greater than 3.5 mg/kg per day and/or calcium to creatinine ratio greater than 0.20 [8]. Uric acid excretion was expressed as uric acid excretion factored for glomerular filtration, according to Stapleton's and Nash's formula [9]. Normal values were lower than 0.57 mg/dl of glomerular filtration rate in 24-hour samples. Mean values were statistically analyzed by Pearson's linear correlation and analysis of variance (ANOVA). RESULTS: Urinary sodium concentration values including urinary sodium to potassium ratios, are shown in Table 1. We found that urinary sodium excretion was significantly increased in patients of both L and C groups when compared with controls (p < 0.05). Further analysis of the subgroups showed that urinary sodium excretion was significantly higher only in patients with hypercalciuria of both L and C groups in comparison to controls (p < 0.05) (Table 2). A significant positive correlation was found between 24-hour urinary sodium to creatinine ratio and urinary calcium to creatinine ratio (r = 0.31; p < 0.001) (Graph 1), as well as between urinary sodium to potassium ratio in 24-hour and first morning urine (r = 0.69; p < 0.001) (Graph 2). (A

[Continuous ambulatory measurement of blood pressure in children--personal experience]. / Kontinuisano ambulatorno merenje krvnog pritiska kod dece--nasa iskustva.

UNLABELLED: Ambulatory blood pressure monitoring (ABPM) during normal daily activities and during night, when the patient is asleep, is a new method of measuring blood pressure (BP) in children, used for better diagnosis and treatment of hypertension. Compared to casual BP measurements, it documents normal daily BP variations, BP during sleep, the influence of emotional and physical stress on BP and is a better predictor of hypertension associated with end-organ damage. However, the experience in ABPM in children is still limited. In our country ABPM has been used since recently, and first results are referred to children with end-stage renal failure. SUBJECTS AND METHODS: ABPM was performed in two groups of children: group A consisted of 61 children, aged 14.3 +/- 2.9 (mean +/- SD) yrs in whom intermittent outpatient BP measurements (for at least 3 months) suggested the diagnosis of hypertension (according to the data of Second Task Force); group B consisted of 52 patients (pts), aged 12.8 +/- 4.6 yr with renal disease. Four pts from group A (6.6%) and 20 pts from group B (38.5%) received antihypertensive therapy (captopril, nifedipine, furosemide and propranolol ). All children from group A and half of the children from group B had normal renal function. Eighteen pts from group B were on chronic haemodialysis (34.6%). Blood pressure was recorded during a 24-hour period except in haemodialyzed pts (48 h) (Table 1). Results of BP measurements are presented as the mean values of BP during a 24-hour period, during normal daily activities and during sleep. We used the age- and gender-appropriate 95th percentile from the Task Force Study as the daytime upper-limit of normal and 10% lower for the upper-limit at night. According to BP load (the percentage of BPs exceeding the upper limits of normal for age), children were assumed to have mild-to-moderate hypertension (BP load between 20% and 40%) or severe hypertension (BP load more than 40%). The success of antihypertensive therapy was evaluated after 1-3 months in 11 pts (twice in 10 pts and three times in one pt). RESULTS: In group A 39.4% of pts were normotensive and 36.1% were without antihypertensive therapy, 58.4% of normotensive and 40.5% of hypertensive pts had blunted circadian BP rhythm (nocturnal BP reduction of less than 10% of diurnal values) (Graph. 1). In group B 38.5% of pts were normotensive and 27% were without antihypertensive therapy. In the group of normotensive pts alteration of circadian BP rhythm was found in 40% of pts with normal renal function, 80% of pts with chronic renal failure and in 100% of pts with terminal renal failure, while in the hypertensive group, altered circadian BP rhythm had 68%, 100% and 92% of pts, respectively (Graph 2). Mild-to-moderate hypertension had 54% of hypertensive pts from group A and 37.5% of hypertensive pts from group B. Severe hypertension was more frequent in group B (62.5%) comparing to group A (46%). The effectiveness of antihypertensive therapy was assessed in 11 pts. In 69.2% of pts BP became normal or was significantly decreased, in 23.1% of pts BP was not changed and 7.7% of pts had higher values of BP. DISCUSSION: ABPM is very useful for diagnosing white coat hypertension. Like other authors, we have pointed out that more than one third of pts who were hypertensive according to usual BP measurements had normal 24-hour BP and we classified them as white coat hypertensives. More than a half of the pts had blunted circadian BP rhythm, and as it is not certain whether they will become hypertensive in adulthood they should be periodically controlled. There are several proofs that results of ABPM have a better correlation with hypertensive end-organ damage; therefore ABPM is used for assessing the severity of hypertension. In our former work, we showed excellent correlation of BP with left ventricular mass index in children with end-stage renal failure. (ABSTRACT TRUNCATED)

[Continuous ambulatory blood pressure measurement--a new method for the detection of arterial hypertension in children]. / Kontinuisano ambulatorno merenje krvnog pritiska--nov metod u otkrivanju arterijske hipertenzije kod dece.

Blood pressure measurements obtained in a physicians office may not reflect the patients blood pressure during the whole day. Ambulatory blood pressure monitoring provides information about blood pressure during normal daily activities and night sleep. Further, the results of ambulatory blood pressure monitoring are in excellent correlation with end-organ damages. The paper discusses the chronobiology of blood pressure, the clinical use of ambulatory blood pressure monitoring, including the identified patterns of blood pressure, the correlation with end-organ damage and its use in clinical trials of antihypertensive medications.

[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.