[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.

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.

[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.

[Kidney transplantation in children]. / Transplantacija bubrega kod dece.

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.

[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.

[Cystic tumefaction in the minor pelvis--the agenesis-dysplasia syndrome (case report)]. / Cisticka tumefakcija u maloj karlici--sindrom agenezije-displazije (prikaz bolesnika)]

UNLABELLED: 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. IN CONCLUSION: 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.

[Jeune's syndrome (3 case reports)]. / Zenov sindrom (prikaz tri bolesnika).

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.

[Urinary bladder dysfunction and vesicoureteral reflux in patients with enuresis]. / Disfunkcija mokracne besike i vezikoureterni refluks kod bolesnika s enurezom.

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 as a familial disease]. / Vezikoureterni refluks kao porodicna bolest.

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.

[The effect of hemodialysis on endothelin-1 plasma levels in children with terminal renal insufficiency]. / Uticaj hemodijalize na nivo endotelina-jedan u plazmi dece s terminalnom insuficijencijom bubrega.

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; p < 0.05). 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.