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.

[What is new in nephrotic syndrome?]. / Sta je novo o nefrotskom sindromu.

This paper reviews the recent achievements in our understanding of glomerular and tubulointerstitial cell biology, their function and disfunction as well as the role in the pathogenesis of the glomerular diseases, namely the nephrotic syndrome. What is new is a major change in our general view of immune inquiry of the tissues. It has been realized that, far from being simple recipients of iqurious stimuli, the cells of the organ may participate in the events of injury in active ways: secretion of cytokinese, eicosanoides, growth factors, complement components, expression of procoagulant factors, MHC class I and II molecules and adhesion molecules. Although we understand much more about pathogenesis of the nephrotic syndrome, this additional knowledge has not resulted, so far, in better treatment. For the time being there are only attempts to improve treatment by affecting mediators (cytokines, growth factors), inhibit cell signaling or cell to cell contact.

[Percutaneous biopsy of the kidney in children (technical aspects)]. / Perkutana biopsija bubrega kod dece (tehnicki aspekt).

The paper analyzes 111 percutaneous kidney biopsies done over the last six years in 107 children (sixty-two patients were female and forty-five male), aged from 1 to 18 years (mean 9.5 years). The authors evaluate advantages of percutaneous biopsy of kidney in obtained an adequate tissue sample for histopathological diagnosis as compared to technical problems and complications regularly associated with the method. All biopsies were performed under local anaesthesia with Tru-Cut[symbol: see text] needles (14 gauge). In 107 biopsy specimens (96.4%) the tissue sample was adequate for histopathological analysis. Following the biopsy, the kidney was routinely scanned to detect a hemato-urinoma. Complications occur in sixteen patients (14.4%). Percutaneous kidney biopsy in children is a safe an reliable technique for obtaining adequate samples of renal tissue for histopathological analysis.

[Cystic kidney disease--genetics, pathogenesis and clinical aspects in children]. / Cisticke bolesti bubrega--genetika, patogeneza i klinicka slika u decjem dobu.

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 (Popovic-Rolovic M, Kostic M, Sindic M. et al Progressive tubulointerstitialnephritis and chronic cholestatic liver disease.

[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.