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The anti-proliferative activitiy of Hypogymnia physodes methanol extracts (ME) and its main constituents, physodalic acid (P1), physodic acid (P2), and 3-hydroxy physodic acid (P3), was tested on human cancer HeLa cell lines. Three lichen depsidones, P1, P2 and P3, were isolated from H. physodes ME using column chromatography and their structures were determined by UV, ESI TOF MS, 1H and 13C NMR. The content of P1, P2 and P3 in ME was determined using reversed-phase highperformance liquid chromatography with photodiode array detection. P1-3 represented even 70 % of the studied extract. The HeLa cells were incubated during 24 and 72 h in the presence of ME and depsidones P1, P2 and P3, at concentrations of 10-1000 μg/ml. Compounds P2 and P3 showed higher activity than compound P1. Half maximal inhibitory concentrations (IC50, μg/ml) of P1, P2, P3 and ME for 24-h incubation were 964, 171, 97 and 254 μg/ml, respectively, while for 72-h incubation they were 283, 66, 63 and 68 μg/ml. As far as we know, this is the first report on the effect of H. physodes ME and their depsidones on HeLa cells.

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%; p0.005) 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.

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.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).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 (p0.05). 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 (p0.05) (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; p0.001) (Graph 1), as well as between urinary sodium to potassium ratio in 24-hour and first morning urine (r = 0.69; p0.001) (Graph 2). (A

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.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.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 (p0.05). 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 (p0.05). 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 (p0.05). 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; p0.01).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)

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.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).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.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)

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.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.Serum OC levels were significantly different in all groups (p0.01); 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 (p0.01), with a positive correlation between OC and duration of haemodialysis (p0.05), as well as between OC and serum phosphate (p0.05), 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 (p0.01), 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 (p0.001), 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.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.

During the last 14 years, since the opening of the Center for Childrens' Hemodialysis the University Children's Hospital of Belgrade, 174 children with terminal renal failure were treated by chronic hemodialysis. Of these, only 35 patients (20.1%), 14 girls and 21 boys, mean age 12.6 +/- 4.9 years, were transplanted. The average waiting time for transplantation was 24.6 months (range 0-120 months). Twenty-five patients were transplanted with paternal kidney, the others were cadaveric transplantations. More than half of transplantations were done abroad. Of 35 patients, 20 were under follow-up for over 6 months (45.7 +/- 7.2 range 6 to 102 months). Five year patient survival was 94.1% and the graft survival over the same period was 76.4%. 45.7 +/- 7.2 months after transplantation the outcome was the following: 11 patients (55%) had GFR over 60 ml/min/1.73 m2, 5 patients (25%) had GFR from 25 to 60 ml/min/1.73 m2, 2 patients (10%) returned to chronic hemodialysis, 1 patient was retransplanted and 1 patient died. All patients with GFR of over 60 ml/min/1.73 m2 are well psychosocially rehabilitated, 62.4% are normotensive without antihypertensive therapy, and only 9.9% are growth retarded.

Recent evidence suggests that circadian blood pressure changes are common in patients with impaired renal function and has excellent correlation with end-organ damage. The aim of this paper was to: 1) evaluate if children with end-stage renal failure have altered circadian blood pressure rhythm; 2) assess whether pre- or postdialytic blood pressure is representative for the average interdialytic blood pressure; 3) assess whether pre- or postdialytic blood pressure is representative for the average interdialytic blood pressure; 3) determine influence of pre-, post and interdialytic blood pressure. Ambulatory blood pressure monitoring was performed in two groups of patients: group A-13 children with end-stage renal failure, aged 15.15 +/- 5.58 years, on chronic haemodialysis from 2 to 156 (mean 45.3) months, 4 of whom were hypertensive and 9 normotensive; group B-19 children with chronic hypertension (essential or renal hypertension) aged 15.28 +/- 2.27 years. 84.62% of children from group A and 31.58% from group B (p = 0.0037) had blunted circadian blood pressure rhythm (a nocturnal reduction of blood pressure is less than 10% of daytime values). Pre- and postdialytic systolic, diastolic and mean arterial blood pressure did not differ significantly and were in correlation with interdialytic blood pressure (r = 0.9; p0.01). Pre-, post- and interdialytic blood pressures correlated well with left ventricular mass index (r = 0.6; p0.05), but were not in correlation with the degree of hypervolemia (p0.05).

This paper reviews recent studies producing insight into genetics and cellular abnormalities causing kidney cysts, their growth and development. Clinical features of various cystic kidney diseases in our patients are described. Special attention has been paid to those rarely reported in our literature. Important discovery concerns location of the gene for autosomal dominant polycystic kidney disease (ADPKD) 1 and 2 on the short arms of chromosome 16 and 4 respectively, as well as for autosomal recessive polycystic kidney disease (ARPKD) on chromosome 6 and for juvenile nephronophtisis on the short arm of chromosome 2. Two basic abnormalities necessary for cyst formation are increased: epithelial cell proliferation and altered fluid transport. Mitogenic action of epidermal growth factor (EGF) is significantly increased and EGF receptors have been demonstrated on apical as well as on basal surface of cyst lining epithelium. TGF-beta shows marked loos of inhibitory activity with regard to EGF. Cystic epithelium has altered polarity; Na-K-ATP-ase is located exclusively on the apical cell membrane. Tubular basement membrane shows alteration in structural components. Complex medullar cystic disease--nephronophtisis, complex as well as the hepatorenal complex of nephoronophtisis--congenital hepatic fibrosis are emphasized in this paper. The later has proved to be rather frequent in our population. We described a distinctive variant of hepato-renal disorder in 4 patients and reviewed 5 similar patients in the literature. The main characteristics are progressive tubulointerstitial nephritis and cholestatic liver disease. We strongly suggest that this variant represents a new syndrome (Popović-Rolović M, Kostić M, Sindić M. et al Progressive tubulointerstitialnephritis and chronic cholestatic liver disease.

We analysed the effect of hemodialysis (HD) on endothelin (ET) plasma level in children with terminal renal failure. Twenty-five patients (pts) and 27 healthy children as controls were included in the study. There was no difference in ET plasma levels in pts before HD (1.97 +/- 1.45) and controls (2.08 +/- 1.47), but ET increased in plasma of pts after HD (4.10 +/- 3.66). To estimate the relationship of volume depletion or depuration on ET plasma level changes in pts during HD, ET was measured at three time points of HD (before ultrafiltration-UF, after UF, and after HD without fluid removal) in 10 pts. ET level was not significantly changed after UF (1.93 +/- 2.25 vs 1.71 +/- 1.50; ns), but was significantly increased after depuration (4.46 +/- 3.56; p0.05). There was no correlation between ET and blood pressure in controls and pts in either period of testing, neither with plasma renin activity, left ventricular mass index, and body weight changes during HD.

Jeune's syndrome or asphyxiating thoracic dystrophy is an autosomal recessive osteochondrodysplasia with multisystem involvement. In patients who survive neonatal period in the main clinical feature progressive renal failure is. Renal lesions are variable but is familial juvenile nephronophtisis the most frequent one. We present three patients with Jeune's syndrome phenotype and chronic tubulointerstitial disease. All patients developed terminal renal failure in the eyrly childhood. Renal histology, examined in two cases, was consistent with juvenile nephronophtisis in one case and with renal dysplasia in other case. All our patients had hepatic fibrosis and two of them had pigmentary retinophaty. We want to underline the importance of regular check-up of children with typical phenotype by pediatrician-nephrologist as wel as possibility of prenatal diagnosis of Jeune's syndrome.

We present preliminary results of prospective study on 38 children (aged 4-15 y.) with enuresis. The aim of the study was to document the association between bladder disfunction and urinary tract abnormalities. Enuresis was more common in girls (71%). Twenty one children (44.7%) suffered from secondary, and 17 (55.3%) from primary enuresis. High incidence of enuresis (31.6%) or voiding dysfunction, renal lithiasis, constipation of other kidney disease (42%) were disclosed among family members of children with enuresis. Urodynamic studies revealed bladder dysfunction in 84.0% of children with enuresis mostly in the form of dyssingeric (45.5%) or unstable/hyperactive bladder (45.5%). In 9% of patients bladder dysfunction as in the form of inadequate bladder with small and poor detrusor contractions often associated with large residue. Ultrasonography revealed dilatation of pyelocaliceal system in 13.2%, and vesicoureteral reflux was confirmed in 10.5% of patients. We stress out high incidence of bladder dysfunction among children with enuresis as well as among their family members.

Vesicoureteral reflux and reflux nephropathy are causes of end-stage renal failure in 43 percent of our patients on haemodialysis. Aiming at early discovering of vesicoureteral reflux and preventing reflux nephropathy, we started an investigation of the familial character or the primary vesicoureteral reflux in the families of 44 our patients with the diagnosed anomaly. Investigations which consist of urinalysis, urine culture and ultrasound of kidneys have so far been carried out for siblings of our patients in ten families. Complete investigations, including voiding cystourethrogram where indicated, have been carried out in five families. Familial vesicoureteral reflux ascertained in three families.

Ectopic kidney often shows signs of parenchyma maldifferentiation. Multicystic or dysplastic kidney is usually associated with congenital urogenital and skeletal system anomalies. In the Unilateral form of the agenesia-dysplasis syndrome, the kidney, if it is present, is small dysplastic and usually cystically changed. Ipsilateral uterus horn or vaginal agenesia are the most frequently associated anomalies. Case report. A six years old girl was clinically examined due to recurrent urinary tract infections. On ultrasound, the left kidney was enlarged, while the right kidney was absent in normal position. Cystic mass 4x5 cm was seen in the pelvis. The right kidney was not seen on IVP. CT scan showed a cystic formation in the pelvis, described as cystically changed dysplastic kidney. Pelviceal mass was extirpated. Exploration of the genital system revealed vaginal arch blinded in the hypoplastic right uterus horn. On pathohystology tumefaction corresponded to the dysplastic kidney.unilateral renal aplasia or dysplasia may indicate genital anomalies having in mind the hereditary character of unilateral form of the agenesia-dysplasia syndrome therefore, it could be helpful in prenatal diagnosis of cystic pelvic mass of fetus in families with this syndrome.

This review discusses the effects of maturation and renal failure on drug disposition and describes drug-induced renal syndromes (nephrotoxicity). Infants and children have age-related differences in physiological and biochemical maturity that alter the pharmacokinetic properties of drugs. Pharmacokinetics are different at birth because of this adaptation period of organ function and because extracellular fluid volume is much larger relative to body size. Postnataly there is an increased in glomerular filtration rate, which reaches adult values at 1 to 2 years of age. Immaturity of tubular functions at birth and during first year of life also modifies the farmacokinetics of drugs. The kidney is the major route of elimination for many drugs and their metabolites. Decrease renal function leads to changes in the pharmacokinetic profiles of various drugs. Adjusting drug dosed in patients with renal failure requires estimates of renal function and the rate of drug elimination, based on the degree of renal impairment. This review provides guideline for the prescribing of drugs in children with end-stage renal disease. As the principal organ of excretion, the kidney is haevily exposed to a variety of foreign chemicals. Exposure is greater when ischemia and endotoxemia are present. This reviewe discusses a number of acute and chronic renal injuries related to drug therapy (nephrotoxicity), limiting discussion to the most commonly used medications. Brief consideration is also given to some important examples of immunologicaly mediated renal injury.

The article deals with the evaluation of the significance of surface antibodies in urinary sediment bacteria by direct immunofluorescence in children with urinary tract infection caused by Escherichia coli (E. coli), so as of determination of location of the infection. Sixty five children were studied, aged from 1 to 16.5 years. Based on the recognized criteria in literature, all patients were classified into three groups: chronic pyelonephritis (CP)--10 patients, acute pyelonephritis (AP)--34 patients, and lower urinary tract infections (LUTI)--21 patients. On the basis of the analysis of the relationship among the three groups of patients in relation to the absence or various presence rates (up to 5%, 6-10% and 11-15% respectively) of fluorescent antibodies in urine sediment, and using the Fischer's test of absolute probability, we obtained a highly significant difference (p = 0.00006) only between the groups AP and LUTI. This difference caused the presence of fluorescence in the AP group and its absence in the LUTI group. By adding the positive fluorescence findings we found that it was present in 80% of CP patients, in 91.17% of AP patients, and in 14.28% of LUTI patients. chi2 test showed a highly significant difference (chi2 = 34.79; p0.01), which confirmed that bacterial fluorescence was most often present in the urine of AP patients and absent in LUTI patients. Bacterial fluorescence was significantly more frequent in CP patients in relation to LUTI patients. These results indicate that the method for detecting surface antibodies in urine bacteria, aimed at determinig the location of infection, is more reliable and noninvasive as compared to other methods.

The purpose of the study was to establish the influence of protein restricted diet supplemented with EAA/KAA on nutritional status of children with CRF. Seven childredn (four girls and three boys), aged from 7 years and eight months to 14 years and two months, with glomerular filtration rate of 42.6-9.2 ml/min/1.73 m2 and proteinuria of 0.025-1.125 g/24 h, who were on conservative treatment and who lived at home, were observed for six months. In prescribing energy value and protein intake WHO recommendations were used for healthly children (age for height). Through food 80-90% of energy and 80-85% of protein needs were provided. The remaining energy and proteins were provided by glucodextrin and EAA/KAA supplements respectevely. Average daily phosphorous intake amounted to about 550-800 mg. The obtained results showed that stunting and kwashiorkor like aminoacid disbalance were the prominent nutritional problems. This dietary regimen had a beneficial effect on all studied parameters. especially on height standard deviation score which increased from 1.71 +/- 2.6 to 1.5 +/- 4.3 (t = 2.809, p0.05); total essential/nonessential aminoacid score increased from 0.38 +/- 0.2 to 0.56 +/- 0.2 (t = 2.763, p0.05). The ratio between plasma concentration of four nonessential (glycine+serinet glutamine+taurine) to four essential (leucine+isoleucine+valine+methionine) amino acids decreased from 3.82 +/- 1.2 to 2.7 +/- 0.4 (t = 2.528, p0.05). Lymphocyte count increased from 1.809 x 10(9) +/- 0.268 x 10(9)/l to 2.314 x 10(9) +/- 0.922 x 10(9)/l (t = 2.431, p0.05). No significant changes were found in the values of relative body weight, arm circumpherence, triceps skinfold thickness, total plasma protein, albumin, transferine, complement C3 and plasma valin/glycin and phenylalanine/thyrosine ratio. It should be noted that the significant changes were not found in the results of these latter anthropometric biochemical parameters in relation to their primary almost insignificant values.

The paper deals with the study of 65 children, aged from 1 to 16,5 years (7 years and 5 months +/- 2 years and 7 months), with urinary tract infection caused by Escherichia coli (E. coli). All patients were classified into three groups according to accepted criteria from literature (clinical features, urographic characteristics, immunological analyses and laboratory signs of inflammatory reaction: (1) 10 patients with chronic pyelonephritis (CP); (2) 34 patients with acute pyelonephritis (AP), and (3) 21 patients with lower urinary tract infection (LUTI). Using 7 antisera antigen preparations O1, O2, 04, O7, O11, O15 and O18, 46 (70.8%) isolated strains were serotyped, while 19 (29.2%) isolated strains of E. coli remained unserotyped. None of the patients showed the presence of more than one serotype in urine. Due to the small number of cases in some groups and low number of serotype strains within the groups, break-down of serotype by patient groups was not done. The prevalent serogroup was O7 found in 22 (47.8%) patients, then O11 in 9 (19.6%), O1 in 4 (8.7%), O15 in 4 (8.7%), O4 in 3 (6.5%), O2 in 2 (4.3%) and O18 in 2 (4.3%) patients. Serogroup O7 was present in all three groups of patients. Statistical analysis showed that the incidence of serogroup O7 was not significantly different (p0.05); this suggests that a specific serogroup does not cause only one type of infection. Having in mind that all existing antisera were not used, the possibility of intra-hospital infection provoked by O7 serogroup should be taken into consideration.

From March 1982 to March 1992 at the Nephrology Department of Belgrade University Children's Hospital 25 patients (16 females and 9 males, aged from 1.5 to 14 years) were treated for hypertensive emergency. Twenty patients had chronic severe hypertension of whom in 19 it was of renal origin. Five patients had acute hypertension during acute poststreptococcal glomerulonephritis. In 15 patients hypertensive emergency was manifested by neurologic disorders, while in the other patients signs of cardiac failure prevailed. Deterioration of renal function was observed in 9 patients and 2 had sec. haemolytic-uremic syndrome. Three patients died during hypertensive crisis, and the others were successfully treated. The fact that in 50% of patients chronic hypertension could not be revealed until the occurrence of hypertensive emergency, suggests the need of its early detection during systemic check-up.

The aim of the study was to assess the frequency of positive anti HCV in the haemodialysis unit (staff and patients) of the University Children's Hospital in Belgrade. Twenty four patients, 14 girls and 10 boys, on chronic haemodialysis from 1 to 164 months, and ten staff members who worked for an average of 9.3 years in the haemodialysis unit, were examined. Patients were screened for HCV antibody in November 1990 (15 pts), July 1992 (14 pts) and September 1992 (13 pts) using the Hepatitis C virus (HCV) 1st generation test for the first check up, and 2nd generation tests for the following ones. Five patients were tested 3 times and 8 twice. Staff members were tested in September 1992 by the HCV 2nd generation test. Complete screening for Hepatitis B virus (HBV) was done by ELISA at the same time as the tests for HCV antibody. All patients and staff members were Hbs Ag negative. Eleven patients and 9 staff members had one or more HBV antibodies due to HBV infection or HBV vaccine. None of staff members had HCV antibody while overall prevalence in patients was high, reaching 50%. It raised with duration of dialysis, and was more frequent in polytransfused and/or patients with positive HBV infection anamnesis.

The aim of this review is to summarize current knowledge about atrial natriuretic peptide--its role in pathophysiology of renal disease. Presumed role of atrial natriuretic peptide (ANP) in renal pathophysiology is based on the study of blood levels and renal effects of ANP in the presence of different manipulations (variations in dietary sodium intake, posture, water immersion or infusion of synthetic ANP) in patients with different renal diseases. In most of nephrotic patients ANP increases diuresis and natriuresis. However, small to great difference in natriuretic response was found in comparing with healty volunteers. Increased release of ANP in humans with chronic renal insufficiency would be expected as consequence of volume overload, diminished glomerular filtration rate and hypertension. Elevated plasma concentrations of ANP in end-stage renal disease are restored to normal level by successful renal transplantation, indicating that renal function is determinant of plasma ANP concentration. Fluctuations in plasma ANP-level during acute renal failure are related to blood volume changes in these patients.

The aim of this review is to summarize current knowledge about atrial natriuretic peptide (ANP)--its structure, secretion and target organ actions. Due to enormous researches, this review is a summary with special emphasis to the physiologic importance of ANP in humans. In the kidney ANP acts on specific receptors inducing hyperfiltration inhibition of sodium transport and suppression of renin release, effects responsible for natriuresis and diuresis. ANP also lowers blood pressure by inhibiting aldosterone biosynthesis and facilitates transudation of plasma water to interstitium. The current knowledge of ANP physiology is based on the study of blood levels and renal effects of ANP in the presence of different manipulations (variations in dietary sodium intake, posture, water immersion, infusion of synthetic ANP). In healty humans ANP levels rise in response to intravenous loading with saline, by acute dietary sodium overload or by immersion of the body into water. Considering these reactions it is possible that ANP helps to protect the heart from volume overload.

Clinical and hystological features of IgA nephropathy were evaluated in 17 children (age range 6 to 14 years). Hematuria was present in all patients (macroscopic hematuria in 10 patients, microscopic hematuria in 7). Mild to moderate proteinuria was present in 10, nephrotic syndrome in two cases. The majority of renal biopsy showed normal picture of mild mesangial proliferation, with crescents in only one patient. Transient impairment of renal function developed in two patients. One of patients progressed to chronic renal failure. Four patients were treated (two with persistent proteinuria, one with nephrotic syndrome, one with nephritic syndrome). Corticosteroid treatment resulted in aggravation of proteinuria in two patients with persistent proteinuria. Patient with nephrotic syndrome demonstrated only diminution of proteinuria during different treatments: corticosteroids, ciclophosphamid and Ciclosporin A. Ciclophosphamid was beneficial in patient with nephritic syndrome.

Expansion of extracellular fluid volume,--increasing right atrial pressure,--appears to be a major stimulus for the rise in plasma atrial natriuretic peptide (ANP). End-stage renal disease (ESRD) is associated with significant changes of several hormone systems. Recent studies have shown that plasma ANP concentration is significantly increased in patients with ESRD and that the concentration of the hormone declines following haemodialysis (HD). In patients with ESRD treated by HD "dry weight" for each individual patient is the body weight at which the patients has normal hydration status. The aim of the present study was to determine changes of plasma concentrations of ANP during haemodialysis. We also attempted to check whether the baseline levels of ANP were related to weight loss during dialysis. Eleven children (7 females, 4 males) participated in the study. The patients age related from 8 to 20 years. Plasma concentrations were markedly elevated (p0.01) before haemodialysis (251 ae 119) pg/ml) in comparison with control values (61 ae 23 pg/ml), but remained above normal range in all except 4 cases. During HD body weight was reduced in all but one patient. This patient was infused isotonic fluid during HD and did not show weight loss. The four patients who had normal plasma ANP levels at the end of treatment appeared to be in better overall condition than the other patients. In summary, plasma ANP measurements may be of value in establishing the volume status in patients with ESRD. Plasma ANP levels after HD may help to adjust the right dry body weight for each patient.

Nine pts, aged 4-20 years (mean 12) with chronic uremic anaemia (mean Hb 5.8 g/dl, range 5.0-7.0 g/dl) on regular thrice-weekly haemodialysis, were treated with human recombinant erythropoietin (rh-uEPO) for a mean of 28.11 weeks (range 4-48). To attain a target Hb concentration (9.6-11.2 g/dl) RH-uEPO (Cilag) was administered i.v. after each dialysis in increasing doses within the range (51-300 U/kg/week). All pts were treated with persantine. Five pts needed iron supplementation. All pts showed increased Hb concentration and none of 6 previously transfusion dependent pts needed further transfusions after the first week of rH-uEPO. Pretreatment long-term dialyzed, polytransfused and iron overloaded pts, even when treated with lower doses of rH-EPO, responded better, reaching target Hb level from the 8th- to the 16th week. Three of 4 highly sensitized pts on rH-EPO treatment had a significant decrease of cytotoxic antibody titre, and 2 were successfully transplanted. rH-EPO also significantly improved the life quality in all pts. No pts developed any serious side affects. There was a transient increase in BP (2 pts) and transaminase with eosinophilia (4 pts).

From June 1987 to June 1991 at the Belgrade University Children's Hospital 10 patients, 5 males and 4 females, aged 2-16 years, with chronic glomerular disease, were treated with CyA. Seven patients had INS, 2 lupus nephritis and one IgA nephritis. Before initiation of CyA, all but one, were treated with classic immunosuppressive therapy, which had no effect (8/10) and/or had serious adverse effects (9/10). CyA dosage was initiated at 4-6 mg/kg/BW, and was subsequently adjusted to achieve CyA concentrations in blood at range 50-100 ng/ml. Treatment duration was 2-17 months. Patient compliance to CyA therapy was observed in 5/7 INSs: 2 cortico-sensitive (1 with FSGS was cortico-dependent and 1 had frequent relapses) and 3 cortico-resistant patients (2 with FSGS and 1 with minimal histologic changes). After drug withdrawal, only one of the patients who responded, had no relapse. One of the two patients with SLE showed improvement during CyA administration, while no response was observed in the patient with IgA nephritis. Adverse experiences with CyA therapy involved decreased renal function (2/10), arterial hypertension (1/10), hyperbilirubinaemia (1/10), transient LDH increase and hyperuricaemia (1/10).

Retention of beta-2-microglobulin, due to loss of excretory renal function inevitably occurs in uremia. A significant correlation between the duration of hemodialysis and the incidence of carpal tunnel syndrome or destructive cystic lesions of bone has been reported. Amyloid deposition has been found to directly cause these lesions. This amyloid protein has been identified to be beta-2-microglobulin. The aim of this report was to study plasma beta-2-microglobulin levels in hemodialysed children and to detect clinical manifestations or carpal tunnel syndrome and of bone lesions. 12 children aged 9-24 years were studied. The average duration of dialysis was 51.9 ae 32 months. Beta-2-microglobulin plasma levels were studied before and after hemodialysis treatment. All patients were examined for carpal tunnel syndrome using clinical methods including nerve conduction studies, and for destructive cystic lesions using X-rays of bone. Plasma beta-2-microglobulin concentrations in our patients were found to be sevrefold time higher (73.8 ae 22.1 mg/l) than control values (1.6 ae 0.5 mg/l). The increase of beta-2-microglobulin concentration during hemodialysis tratment was due probably by hemoconcentration. We noted poor correlation between plasma beta-2-microglobulin and duration of hemodialysis. Any signs of carpal tunnel syndrome was found to our patients. Radiological signs of amyloid osteopathy found to be present in 3 children, was not verified by bone biopsy.

Seven patients, 4 girls and 3 boys, aged 3 to 12 years /X = 7.14/ affected by haemorrhagic fever with renal syndrome /HFRS/., were hospitalized at the University Children's Hospital in Belgrade during the last two years /January 1988-January 1990/. The diagnosis was established on the basis of clinical features, epidemiological data and autopsy findings in one patient while in the others the diagnosis of HFRS was confirmed serologically by indirect immunoflorescence tests on Vero E 6 cells. A significant increase in antibody titre against Hantaan virus was found in all serologically tested patients. Three of them had also significant increase of antibody titre against Soeul and one against Puumale virus. In four patients the disease appeared as family outbreak at the end of January 1988 while the others were sporadical cases. All patients but one mentioned contact with rodents at home or in fields. The predominant slynical symptom were: sudden onset of febrile condition with headache, generalized malaise, myalgia, abdominal pain, vomiting, diarrhoea, oliguria and oedema. All patients had haematuria and only one had other severe haemorrhagic manifestations. Four patients were hypertensive. Two patients had renal insufficiency, but only one required haemodialysis. Five patients recovered after 2 to 8 weeks without sequellae, one patient was still /7 months after the beginning of the disease/ in mild renal insufficiency and one patient died. Autopsy findings showed tubular necrosis in the kidney, myocarditis, massive pneumonia with hydrothorax and jejunal haemorrhagia.

Optimal conditions of HSA aggregation in acetate buffer (pH = 4.6) were investigated. With the aim of obtaining a higher percentage of fixation in the lungs, the aggregates were rinsed three times with acetate buffer. A MAA suspension was lyophilized with SnCl22H2O (10 microgram/ml) solution. The lyophilized MAA was then labelled by adding pertechnetate of the desired activity in a volume of up to 5 ml. The radiochemical purity of 99mTc-MAA, greater than 95%, was determined by the methods of thin layer chromatography and low-voltage electrophoresis. All MAAs were uniform in shape whereas the size varied between 20 and 100 micrometer. Biodistribution studies have shown the maximum radioactivity to be deposited in the animals' lungs immediately after application of 99mTc-MAA.

In this paper, the author analyses the impact of the COVID-19 pandemic on internal and external aspects of insurance organizations, and particularly on insurance terms and conditions. The introductory part provides general remarks on the impact of the pandemic on community and economy, also defining the subject of the paper. In the second part, the author explores how insurers responded to new working conditions and behaved in relation to their self-organization and to the public and the insured persons. Particular developments in a macroeconomic and political context relating to covering losses from COVID-19 are also analyzed. The author concludes that a certain delay in making the amendments and supplements to the list of communicable diseases was justified, whereas the main characteristic of extended cover for COVID-19 provided by domestic insurers is not the reimbursement of medical treatment costs but the payment of daily allowance and provision of information and particular services. In addition, the author concludes that wordings used to exclude the risk of communicable diseases may create particular dilemmas as to whether a loss event may be considered insured, depending on the circumstances and time of its occurrence, and depending on the provisions of positive legal regulations.