Heterogeneity of atypical haemolytic uraemic syndromes.

Atypical, non-diarrhoea associated haemolytic uraemic syndrome (D-HUS) is a heterogeneous disorder with a generally poor outcome, although this view has now been questioned. The clinical and laboratory features of 23 children with D-HUS, representing a third of all patients with HUS seen during the last 26 years, were examined. The median age was 4.9 years (range 3 days-13.8 years). Twenty one children (91%) survived the initial phase. All patients except six infants aged < 18 months required dialysis (74%). Hypertension (43%), cardiomyopathy (43%), and cerebral convulsions (48%) were common. Nineteen (83%) children were followed up for a median period of 5.5 years (range 0.5-23.4). Only five (26%) patients, among them four infants, recovered completely. Six (32%) patients had one to 10 recurrences, including two siblings with neonatal onset, and eight (42%) developed end stage renal failure. Five children underwent cadaveric renal transplantation, with recurrence and subsequent graft failure in two. Four children died, resulting in an overall mortality of 26%. Atypical HUS is heterogeneous with regard to epidemiology, pathophysiology, and outcome. Children with a recurrent, familial, or neonatal course have worse outcomes; in contrast, infants not requiring dialysis in the acute phase have a better prognosis.

Renal-hepatic-pancreatic dysplasia: an autosomal recessive disorder with renal and hepatic failure.

UNLABELLED: We report two brothers with renal dysplasia and congenital hepatic fibrosis. One patient died shortly after birth of lung hypoplasia. The second developed end-stage renal failure at 14 months. The hepatic fibrosis progressed to cirrhosis and hepatic failure. Pancreatic function was normal, but increased echogenicity was seen on ultrasound. At age 3 years and 9 months a successful combined liver-kidney transplantation was performed. The features of our patients are compatible with the "renal-hepatic-pancreatic dysplasia" syndrome. CONCLUSION: Renal-hepatic-pancreatic dysplasia is an autosomal recessive disorder with variable expression. Combined liver-kidney transplantation offers a new therapeutic option.

Long-term low-dose cyclosporin A in steroid dependent nephrotic syndrome of childhood.

Therapy of steroid-dependent idiopathic nephrotic syndrome is often unsatisfactory. Since 1986 we have treated nine children (six male and three female), aged 3-16 years, with cyclosporin A (CsA) during 2.0-5.2 (median 3.1) years. All had minimal change disease on renal biopsy and had previously received cyclophosphamide. Mean daily dosage of CsA was 4.1 mg/kg (range 2.7-5.8) and mean whole blood trough level was 220 ng/ml (range 141-271). The relapse rate decreased from 3.4/patient year before CsA to 0.55 on CsA. Discontinuation of CsA or reduction below 2 mg/kg daily was always followed by a relapse. The overall relapse rate, including the period with very low-dose CsA, was 0.95/patient year. Four patients required additional low-dose alternate-day prednisone. Repeat renal biopsy showed minimal change disease in eight patients and focal segmental glomerulosclerosis in one; CsA-toxicity was mild in two and moderate in one. The latter was the only patient with slightly reduced glomerular filtration rate. Two boys with delayed puberty spontaneously matured and reached expected final height. We conclude that long-term low-dose CsA is very effective and steroid-sparing. Its use is justified in selected patients, particularly in those with numerous relapses and in male patients before and during puberty, as long as renal function and CsA-toxicity are carefully monitored.

Epoetin alfa in anaemic children or adolescents on regular dialysis.

Eighteen patients aged 5-18 years on regular dialysis had a packed cell volume (PCV) less than 0.27. On treatment with epoetin alfa (EA) PCV increased by 0.05 or more in all patients. Iron supplementation was necessary in 13 patients with a ferritinaemia less than 300 micrograms/l before study. During treatment, plasma potassium increased significantly and more vigorous antihypertensive measures were required in 8 patients, 5 of them being already on antihypertensive drugs before EA. Iliofemoral thrombosis occurred in 1 patient 10 days after renal transplant. The data indicate that EA ameliorates the anaemia of chronic renal disease. The main concerns arising during treatment with EA are hyperkalaemia, arterial hypertension and possibly thrombosis.

Urinary oxalate and glycolate excretion in healthy infants and children.

The molar ratios of oxalate and glycolate over creatinine were determined in single urine samples of 26 infants and 27 children aged 1-5 years. In 135 children aged 5-16 years, two urine specimens were collected, one before breakfast and one at noon. Oxalate was determined by oxalate oxidase, and glycolate was measured by a colorimetric method (improved chromatotropic acid--sulphuric acid assay after prior purification by cation and anion exchanger). Both ratios (expressed in mmol/mol creatinine and analysed on a log-normal basis) were highest in infants 0-6 months old [mean oxalate 147 (95% confidence interval: 60-360), mean glycolate 175 (72-425)]. The mean oxalate ratio was 72 mmol/mol (29-174) at the age of 7-24 months, 44 (19-101) at the age of 2-5 years and 22 (12-40) in adolescents aged 16 years. Molar glycolate ratios were higher, but disclosed the same pattern. Oxalate and glycolate ratios in fasting urines did not differ significantly from those in noon samples (except glycolate in the oldest age group). Oxalate ratios correlated well with glycolate ratios in children up to 5 years of age only. Random urine samples are thus suitable for screening. However, interpretation of data requires use of age-specific reference values that are based on comparable methods.

Ambulatory blood pressure recording in children and adolescents with a semi-automatic recording device.

The blood pressures of 169 hospitalized children and adolescents were determined by a semi-automatic recording device (Sysditon). Several technical modifications of the paediatric cuffs were required before the device yielded satisfactory results. The systolic pressures then agreed very well with conventional sphygmomanometry, whereas the diastolic pressures were underestimated by 2.6 to 5.9 mm Hg and showed considerable scattering. In the second part of the study, 28 children and adolescents performed home recordings during one week. These measurements were compared with the hospital recordings obtained before and after the home recordings. The mean of all systolic self measurements was lower by 3.4 mm Hg than the initial hospital recordings, whilst the final hospital recordings were almost identical. In the majority of children, the lowest home recordings were noted in the morning and at noon, and the highest values in the afternoon and evening. Self measurement with a semi-automatic device is a simple and inexpensive method to evaluate elevated blood pressure and to control anti-hypertensive therapy of children and adolescents. However, technical modifications of the cuffs are necessary, and the devices need careful evaluation before being used in children.

New aspects of infantile oxalosis.

Infantile oxalosis is the most severe form of primary hyperoxaluria type I (PH I). Only 28 patients have been reported in detail; it was found that diagnosis was usually delayed, and most patients presented before the age of 4 months in renal failure and died within the 1st year of life. This report comprises two infants in whom diagnosis of PH I was made in the first few weeks of life before renal function was impaired. Case 1, whose brother had died of infantile oxalosis, already had greatly increased urinary oxalate and glycolate excretion at 7 days of age. In Case 2, PH I was diagnosed early because of the finding of increased renal echogenicity at 3 weeks of age; this patient had numerous episodes of stone formation despite continuous treatment with pyridoxine, but maintained renal function with normal serum creatinine levels at the age of 28 months. Prenatal diagnosis was attempted in case 1; however, amniotic fluid oxalate and glycolate concentrations were normal, suggesting that these acids pass the placenta and are not retained. The recent discovery of a transamination defect (deficiency of the peroxisomal enzyme alanine: glyoxylate aminotransferase) explains why some patients respond to pyridoxine treatment. Differences in onset and severity of PH I and in response to pyridoxine suggest that this disorder is biochemically and genetically heterogeneous.

[Nutrition of pediatric patients with chronic renal failure]. / Die Ernährung pädiatrischer Patienten mit chronischer Niereninsuffizienz.

Adequate nutrition plays a key role in the conservative management of chronic renal failure. Recent experience favours initiation of dietary measures at an earlier stage of renal failure (RF) than hitherto advocated. The requirements of protein and energy are preferably calculated according to height rather than age. Protein intake is often far in excess of the recommended (minimum) intake of 0.25 g per cm body height (taken as 100%). With the aim to keep serum urea concentration close to normal, intake in mild RF (GFR 33-50 ml/min per 1.73 m2) is restricted to 150%, in moderate RF (15-33 ml/min) to 120%, and in severe RF (less than 15 ml/min) to the minimum. High quality protein (greater than 70% of animal origin) is advocated in case of severe restriction. Further limitations are possible with administration of essential amino acids and keto analogues. Energy requirements vary with height (56-75 kJ per cm body height). Many patients require a supplementation, e.g. oligosaccharides. Intestinal phosphate absorption (and renal excretion) is adjusted according to the degree of RF by reduction of intake and administration of phosphate binders (aluminium hydroxide or calcium carbonate). Vitamin D is now often given as one of its polar metabolites. Severe dietary restrictions require a high motivation of the patient, family and staff and are only successful when a good state of health can be maintained.

[5 years of continuous ambulatory peritoneal dialysis in the child]. / 5 Jahre kontinuierliche ambulante Peritonealdialyse beim Kind.

Ten patients aged 5-14 years and 1 adolescent were treated by CAPD during 12 patient years. Overall survival and rehabilitation were good despite relatively high serum concentrations of urea (19 mmol/l) and creatinine (735 mumol/l). Dietary restrictions were only occasionally necessary, 6 patients required phosphate binders. No radiological bone changes developed in 4 patients with initially normal x-rays, but lesions progressed in 3 with pre-existing osteodystrophy despite administration of 1.25 (OH) 2D3 and Al-hydroxide. Statural growth was unsatisfactory: Height decreased in the 7 patients observed over 1 year from -2.4 to -2.7 SDS. Peritoneal diffusion curves varied considerably between patients, yet remained unchanged at repeat examination. Parents fatigue developed in 6 families and was partly responsible for peritonitis. The incidence of peritonitis fell from 1 episode in 3.3 months to 1 in 8 months. Intensive family support by regular telephone contact and home visits appeared as the most important measure in prevention of parents fatigue and hence of peritonitis. We consider CAPD as a valuable alternative method to haemodialysis.

Physiologic increase and tracking of blood pressure in schoolchildren.

4343 blood pressure (BP) recordings were obtained in 1575 schoolchildren during 5 years. Systolic BP rose proportionally to upper arm muscle area (MA) in both sexes. In contrast, upper arm fat area (FA) was considerably lower in boys than in girls, and the rise of systolic BP in boys during puberty was not accompanied by any increase of FA. At repeat examination of 900 children after 1 to 5 years, between 35% and 53% of those with initial systolic BP in the highest quintile had again values in the same quintile, thus twice as often as expected. Tracking in the highest decile was even stronger: 37% of 82 children had again systolic BP in the highest decile at 2 years, and 29% at 4 to 5 years. We conclude that the physiologic increase of systolic BP is primarily determined by rising muscle mass, and tracking still remains detectable in children after 4 to 5 years and is strongest in those with highest values.

Cuff-associated errors of blood pressure recording in infants and toddlers.

As commercially available cuffs are unsatisfactory, systolic blood pressure (BP) was measured in 88 children aged less than 4 years using a conventional Velcro self-adhesive cuff with inflatable bladder. Results were compared with the "separate bladder" method (where the inflatable bladder is wrapped around the arm and is held by a separate Velcro-band), the Pedisphyg cuff and, in 10 patients, with intra-arterial recording. The last 3 methods gave nearly identical results. In contrast, conventional cuffs with a 4 cm and a 5.5 cm wide bladder considerably over-estimated systolic BP, by 13.3 mm Hg (range -2 to 30) for bladder width 4 cm, and by 13.1 mm Hg (range 4 to 22) for bladder width 5.5 cm, respectively. The conventional bladder-cuff thus yields grossly inaccurate results in young children and should be replaced by an alternative method, e.g. the "separate bladder".

[Acute interstitial nephritis and uveitis: a recently recognized syndrome]. / Akute interstitielle Nephritis und Uveitis: ein neu erkanntes Krankheitsbild.

The case is described of a 14-year-old boy who presented with a 6-week history of fatigue, severe weight loss (15 kg) and glycosuria. On admission he was in non-oliguric renal failure (serum creatinine 1360 mumol/l) with moderate proteinuria (1.3 g per 24 h), glycosuria (9.5 g per 24 h) and generalized aminoaciduria. Renal biopsy showed acute interstitial nephritis (AIN) with severe mononuclear cell infiltration. No etiology was found. The patient required hemodialysis (5 times) and responded dramatically to therapy with prednisone (initially 75 mg per day), which was discontinued after 2 months. He presented again 11 weeks after admission with iridocyclitis of the right eye, and 2 months later with the same condition in the left eye. Response to local application of steroids was slow. The association of AIN with uveitis has so far been reported in 12 other pediatric patients aged 10 to 16 years, and in one adult patient; 64% were female. Uveitis often recurred, in contrast to nephritis. The etiology of the syndrome is unknown, a transient defect in cell-mediated immunity being postulated.

Primary hyperoxaluria: an important cause of renal failure in infancy.

All 25 infants with primary hyperoxaluria type I (PH) so far reported in detail (including one own observation) presented in renal failure (RF) whereas urolithiasis has conspiciously been absent. Diagnosis of PH was often delayed due to nonspecific symptoms of RF: Vomiting, anemia and severe metabolic acidosis. However, demonstration of increased renal echodensity at ultrasound examination should allow early diagnosis. A flecked retina has been noted in several infants. In contrast, our patient had black retinal pigmentations which have only once been reported in PH. Prognosis in untreated patients has so far been poor: 67% died within the first 6 months of life. It is likely that early diagnosis and treatment will improve prognosis in the future.

Outcome of pediatric patients with end-stage renal disease in Switzerland 1973-1982.

The annual incidence of end-stage renal disease (ESRD: 1.32 patients aged 1/2-16 years per million population or 6.5 per million children of same age) and the causes have remained remarkably constant over the last 15 years in Switzerland. 58 patients (69%) were treated by dialysis and/or renal transplantation. The overall survival rate was 77% at 5 years and 65% at 10 years. 26 untreated patients (31%) died of uremia. They had not been treated despite existing facilities for the following reasons: Young age (7 of the 8 patients being less than 2 years old), psychosocial reasons (6), severe mental retardation (6) and associated problems (6). It is estimated that even in the future 20% of all pediatric patients with ESRD will be considered unsuitable for therapy by dialysis and renal transplantation.

Requirements for paediatric blood pressure cuffs.

Since recommendations concerning the optimal size of blood pressure cuffs (i.e. bladders) are controversial, we performed arm measurements in 162 patients aged 3 weeks to 19 years. The arm circumferences when using bladders 4 cm to 8 cm wide are considerably longer than previously assumed, e.g. 12.5 to 18.5 cm for a bladder 4 cm wide. The requirements for the inflatable bladder are based on these arm measurements and the recommendations to use a bladder that is as wide as possible and encircles at least 60% of the arm (the 4 cm bladder must overlap). Thus, the optimal (minimal) dimensions are: 12 X 24 (19) cm, 10 X 20 (17) cm, 8 X 18 (16) cm and 4 X 20 cm. The blood pressure cuffs available on the Swiss market were then tested according to these specifications. Eleven of 20 cuffs were rated unsuitable in children, and only 6 can be recommended. Thus, there is an obvious need for improvement.

The conventional (Velcro self-adhesive) cuff overestimates blood pressure in infants. Description of a suitable alternative.

Systolic blood pressures were measured by auscultation or with the Parks Doppler system using blood pressure cuffs of various sizes (widths of the inflatable rubber bladders 4, 6 and 7.5 cm). We compared the results obtained by the conventional cuffs with the Pedisphyg cuff-bladder assembly (in which both cuff and bladder coexist) and with a new "separate bladder" method. Here, the inflatable bladder is wrapped around the arm and is held by a separate Velcro band. Readings comparing these methods agreed well when using the 7.5 cm wide bladder, but conventional cuffs with bladders 6 cm and 4 cm wide seriously overestimated blood pressure by an average of 9.0 and 13.3 mm Hg, respectively. The conventional 4 cm cuff should be abandoned, and the "separate bladder" method used instead.

[Recurrence of the original disease in the transplanted kidney]. / Rezidive der Grundkrankheit im Nierentransplantat.

Recurrence of the original disease in the transplanted kidney is observed in 5.6%-9.3% of the patients. However, the clinical significance of recurrence is often minor. Diagnosis is easy in diseases with specific renal lesions, e.g., in dense deposit disease and IgA-nephropathy, but may be difficult if such a marker is missing. Recurrence is of special clinical importance in the following conditions: Membranoproliferative GN type I (in 33%, often severe) and type II (= dense deposit disease, recurrence in 90%, often minor), focal segmental glomerulosclerosis (in 48% of patients with a rapid course (less than 3 years) and in 12% of patients with a longer duration of the original disease; often severe), membranous nephropathy (recurrence rather rare, but often serious), and primary hyperoxaluria (in 100%). Mesangial IgA deposits recur in half of the patients with IgA-nephropathy and anaphylactoid purpura, but clinical findings are often minimal. Recurrence in anti-GBM-nephritis and SLE is rare. The study of recurrence may contribute to a better understanding of many renal diseases.