Plasminogen activator inhibitor type-1 and interleukin-6 in haemolytic uraemic syndrome.

OBJECTIVE: Because haemolytic uraemic syndrome (HUS) is an important cause of renal dysfunction in children, the availability of prognostic markers of disease severity could assist in identifying those at risk of developing long-term sequelae. The aim of this study was to test the hypothesis that plasma levels of plasminogen activator inhibitor type-1 (PAI-1) and interleukin-6 (IL-6) in children at the time of diagnosis of HUS would predict renal function outcome in terms of glomerular filtration rate (GFR). METHODOLOGY: Fourteen children suffering from diarrhoeal HUS were studied. Plasma samples were assayed for PAI-1 and IL-6, and GFR was measured at intervals after discharge from hospital. Twelve months following their recovery from HUS, the children were allocated to one of two outcome groups depending on whether GFR was above (Good Outcome, n = 9), or below (Poor Outcome, n = 5) 80 mL/min per 1.73 m2. RESULTS: Elevated concentrations of PAI-1 were found in 4 of 5 Poor Outcome and 4 of 9 Good Outcome children. At the same time, increased concentrations of IL-6 were observed in 3 of 5 Poor Outcome and 3 of 9 Good Outcome children. Renal function continued to be compromised in four Poor Outcome children 36 months after diagnosis. CONCLUSIONS: Our data show that PAI-1 and IL-6 are elevated in the plasma of some children at the time of diagnosis of HUS, but that neither is a definitive prognostic marker of poor outcome 3 years later.

Renal tract abnormalities detected in Australian preschool children.

OBJECTIVE: To quantify the incidence of abnormalities in urinalysis and blood pressure from preschool children and their predictive value in detecting renal disease within an Australian community. METHODOLOGY: Urine samples, blood pressure and height measurements and parental reports of significant medical problems were collected from a total of 9355 South Australian preschool children. Seven hundred and forty-three children with abnormal results were investigated in a nephrology outpatient clinic. A control group of 357 children with no detectable abnormality were also recalled, examined and, where appropriate, investigated. RESULTS: Nine thousand, three hundred and fifty-five children were tested. Of these, 0.81% were shown to have a clinically significant renal tract abnormality. The findings included children with urinary tract infections, vesico-ureteric reflux, glomerular disease, renal calculi, essential hypertension and a renal neoplasm. While dipstick-based methods were the most specific indicators of renal tract abnormalities, measurement of blood pressure and urinary beta2-microglobulin were also important in detecting abnormalities. Screening for glycosuria did not result in the detection of significant undiagnosed abnormalities. In the control group with no abnormality detected at testing, there was one case each of aortic coarctation, polycystic kidney disease and vesico-ureteric reflux diagnosed. CONCLUSION: Undiagnosed renal tract abnormalities are present in many Australian preschool children. Most are detectable by a thorough history, examination and urinalysis.

Haemolytic-uraemic syndrome outbreak caused by Escherichia coli O111:H-: clinical outcomes.

In South Australia in 1995, we treated 20 children with haemolytic-uraemic syndrome associated with Escherichia coli O111:H-. The source of the outbreak was contaminated locally produced semi-dry fermented sausage (mettwurst). One child died of multiple haemorrhagic cerebral infarcts. Eighteen children required renal dialysis (for a median of 14 days); 12 months after discharge five still had significant impairment of renal function. Other major complications included colonic necrosis (3), cerebral haemorrhage/infarction (3), convulsions (4), and glucose intolerance (2). Although E. coli O111:H- has been associated with sporadic cases of haemolytic-uraemic syndrome, this was the first large outbreak reported in Australia.

Continuous veno-venous hemodiafiltration using bicarbonate dialysate.

We report our experience with 11 children treated by continuous veno-venous hemodiafiltration. The median age was 5.0 years (range 3 days to 14 years). Access was via dual-lumen subclavian or femoral vein catheters. Hemofilters were chosen on the basis of patient size and dialysis requirements. Bicarbonate-buffered dialysis solution was prepared shortly before use by supplementation of a specially prepared base solution with commercially available electrolyte solutions. The mean ultrafiltration rate was 37.4 +/- 27 ml/kg body weight per hour. Urea and creatinine clearances were 15.1 +/- 6.4 ml/kg body weight per min and 16.4 +/- 8.4 ml/kg body weight per min, respectively. Metabolic acidosis was readily controlled in all patients. Of the 11 patients, 7 ultimately recovered normal renal function.

Effects of growth hormone on insulin-like growth factors and binding proteins before and after renal transplantation.

Three short children with severe chronic renal failure were treated with recombinant human growth hormone (rhGH) for 2 years. Each received a transplant in the 2nd year. Serum collected before and during rhGH therapy was analysed retrospectively by Western ligand blot and immunoblotting techniques. In addition, radioimmuno-assays for insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3), acid-labile subunit (ALS) and IGFBP-1 were performed. IGFBPs in serum, detected by Western ligand blot, were identified as IGFBP-3, -2, -1 and -4 by immunoblot. The serum concentration of IGF-I in each child rose approximately fourfold with rhGH before transplantation and subsequently remained elevated. IGFBP-3 levels rose to double the pretreatment value, but dropped to normal levels following transplantation, while ALS rose with rhGH treatment and remained increased after transplantation. IGFBP-1 levels changed little with rhGH but fell following transplantation. A low molecular weight form of IGFBP-3 was noted at 30 kilodaltons on immunoblot which was not clearly seen on the ligand blot. IGFBP-2 was present as a distinct band on Western ligand blot before transplantation and appeared decreased in intensity subsequently. IGFBP-1, seen on immunoblot clearly before transplant, disappeared after the transplant. rhGH successfully improved growth in these children, in association with a fourfold increase in IGF-I levels, which was maintained following transplantation. The reduction in IGFBPs following transplantation suggests correction of impaired clearance by the diseased kidney.

Enhanced body growth in uremic rats treated with IGF-I and growth hormone in combination.

The efficacy of seven days treatment with IGF-I (1.7 mg/kg/day), growth hormone (GH) (2 mg/kg/day), IGF-I+GH (1.7 mg/kg/day + 2 mg/kg/day) or vehicle, in promoting growth was investigated in female Sprague-Dawley rats with 5/6 nephrectomies (N = 8 per group). Treatment commenced after chronic renal failure had been present for seven weeks. Significant increases in body weight gain were found in all groups versus control, with IGF-I+GH causing the greatest response, and increased body weight gains correlating with increased nitrogen retention. GH treatment alone significantly stimulated food intake. IGF-I+GH resulted in close to additive increases in food conversion efficiency (18.8%, 21.5% and 39.6% increases with IGF-I, GH and IGF-I+GH, respectively, over control levels) and longitudinal bone growth (39%, 37% and 67% increases with IGF-I, GH and IGF-I+GH, respectively, vs. control). Serum insulin and cholesterol levels significantly decreased with IGF-I and IGF-I+GH treatment. Creatinine clearance did not change, suggesting there were no effects of treatment on kidney function. Although IGF-I at the doses used did not result in a greater anabolic response than GH, IGF-I+GH caused significantly enhanced growth while reducing serum insulin and cholesterol levels.

Accelerated growth in short children with chronic renal failure treated with both strict dietary therapy and recombinant growth hormone.

In a 12-month study, nine boys, aged 4.8-15.6 years, with bone ages 4.6-13 years, with moderate to severe chronic renal failure and resultant growth failure were treated with daily recombinant human growth hormone (rhGH), in conjunction with a strict low-protein/low-phosphate diet supplemented with keto and amino forms of the essential amino acids, histidine and additional energy. Improved growth had previously been observed with this dietary management over that obtained with conventional treatment for chronic renal failure. Each child had been on this diet for at least 2 years before rhGH was commenced. Mean height velocity increased from 4.6 +/- 1.3 to 9.0 +/- 1.3 cm/year (P < 0.001) in the pre-pubertal group, and in the pubertal group from 5.4 +/- 1.4 to 10.4 +/- 1.8 cm/year (P < 0.01). The mean height velocity standard deviation scores (SDSs) increased from -1.2 +/- 0.6 to +2.3 +/- 0.9 (P < 0.001) in the pre-pubertal group and from -0.4 +/- 0.6 to +1.9 +/- 1.1 (P < 0.01) in the pubertal group. Mean height SDS for chronological age increased from -2.2 +/- 0.7 to -1.5 +/- 0.5 (P < 0.01) in the pre-pubertal group and from -1.9 +/- 0.7 to -1.3 +/- 0.9 in the pubertal group (P < 0.02). There was no significant deterioration in renal function or renal bone disease, and bone age did not advance more than chronological age over the 12-month period.

Evaluation of long-term aggressive dietary management of chronic renal failure in children.

Ten children with chronic renal failure (CRF) were managed for 3 years using a strict low-protein and low-phosphorus diet supplemented by a mixture of the keto and amino forms of the essential amino acids and histidine (phase II). All of these children were previously managed for at least 2 years with a less rigorous diet of limited protein intake with no specific reduction of phosphorus (phase I). Energy, vitamin D, bicarbonate, phosphate binders and vitamin and mineral mixtures were added as required during both dietary phases. Data on dietary intake showed a significant fall in protein and phosphorus intake and a rise in calcium intake during phase II compared with phase I. Plasma calcium increased and phosphate fell, with an associated fall in intact parathyroid hormone levels. There was a marked improvement in urea creatinine ratios, which suggested an improved anabolic state. Cholesterol and triglyceride levels were improved. Height and weight velocity were increased, becoming significant after 3 years of phase II. Renal function deteriorated at a slower rate than predicted. The diet was well tolerated by the children, with fitness and school performance showing improvement. We conclude that long-term strict dietary management of children with CRF is feasible. Our data suggest an overall improvement in general health and an apparent reduction in the rate of deterioration of renal function.

Urinary tract infection.

Between three per cent and five per cent of all girls and one per cent to two per cent of all boys will experience a urinary tract infection (UTI) before reaching puberty. While most of these children do not suffer permanent renal damage, a systematic approach to the management of UTI allows the detection of the minority who are at risk.

Blood pressure in schoolchildren measured under standardized conditions.

The blood pressures of 6346 children who were between the ages of seven and 17 years were measured under standardized conditions. Blood pressures were similar in prepubertal boys and girls. After puberty, the systolic blood pressures of the girls remained unchanged whereas those of the boys continued to rise. The difference between the fourth and fifth Korotkoff sounds was 2 mm at both the 50th and 95th percentiles. The systolic blood pressure was observed to fall over a 10-min period by 4-9 mmHg at the 50th percentile and 9-15 mmHg at the 95th percentile. Over the same period of time, the diastolic blood pressure was seen to fall by 2-3 mmHg and 3-6 mmHg at the 50th and 95th percentiles, respectively. There was no further fall in blood pressure after 10 min. The conditions and timing of measurement are important in blood-pressure evaluation and may explain the differences in blood pressure that have been reported for different populations.

Ultrasound diagnosis of nephrocalcinosis in preterm infants.

The incidence of nephrocalcinosis in very low birthweight (less than 1500 g) premature infants was assessed by ultrasound scan and analysis of urine. Three of 36 infants had nephrocalcinosis. All had been receiving long term frusemide for bronchopulmonary dysplasia with simultaneous fluid restriction. Urinary investigations showed no consistent findings in babies with nephrocalcinosis.

Antigen expression during early human granulocyte development studied with immuno-electron microscopy.

Expression of the hapten fucosyl-N-acetyllactosamine was correlated with ultrastructural development in human granulocyte precursors using the monoclonal antibody FMC 10 with immunogold techniques. The antigen was detectable from the myeloblast/early neutrophilic promyelocyte stage onwards and was associated with striking development of the rough endoplasmic reticular system. In addition, low levels of labelling were seen on monocytes, eosinophils and some basophil precursors. Contraction and alignment of the cisternae of the rough endoplasmic reticulum during the promyelocyte stage of neutrophilic differentiation gave the appearance of a plasma cell. However, on closer examination it was apparent that true plasma cells did not react with this antibody.

Effects of short-term modification of dietary sodium intake on plasma catecholamines and blood pressure in prehypertensive children.

The influence of dietary sodium intake on plasma catecholamines was examined as part of a dietary intervention study in 21 prehypertensive school children. Diastolic blood pressure was significantly elevated in girls after 3 weeks on a high sodium diet compared with a low sodium diet. Plasma adrenaline levels were raised slightly by the high sodium intake but plasma noradrenaline was significantly reduced. Increases of plasma catecholamines in response to standing or cold stress were unaffected by changes in sodium intake. The results indicate that the pressor effect of dietary sodium in children is not attributable to increased sympathetic nerve activity.

Fetal urinary tract abnormalities detected on maternal ultrasound.

Twenty-one cases of fetal urinary tract abnormalities were detected on maternal ultrasound in a 5 year period. Six fetuses died and 13 of the 15 surviving cases have had corrective urological surgery, usually during the neonatal period. Maternal ultrasound provides advanced warning of major urinary tract abnormalities in the newborn. Therefore, appropriate investigations and medical management can be instituted early and potentially destructive urological lesions can be corrected as soon as possible. As yet, antenatal intervention does not seem to be warranted as the most common cause of bilateral upper tract dilatation in the surviving cases in this series was primary reflux, and in the cases that died the urinary abnormalities were not salvagable.