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Neurogenic bladder dysfunction in children is frequently seen in patients with meningomyelocele (MMC). The disorder carries a high risk for all kinds of complications, with renal damage being the most important. More than 95% of MMC patients have a neurogenic bladder, the paramount manifestation of which is a disturbed coordination between detrusor and sphincter muscles. This vesicourethral dysfunction leads to defective filling and emptying of the urinary bladder. Voiding at will is almost never possible. According to the location and extent of the neural tube lesion, patients have either an atonic or a hypertonic pelvic floor and either an atonic or a hypertonic detrusor, leading to four classic combinations. Hypertonic sphincter and detrusor hyperactivity lead to the most dangerous form of neurogenic bladder, referred to as the "unsafe" bladder. The presence of residual urine in a high-pressure container causes either decompensation of the detrusor with vesicoureteral reflux or deterioration of the bladder wall with hypertrophy and stiffness resulting in uterovesical obstruction. The subsequent insufficient drainage of the upper urinary tract leads to decompensation of the ureters and finally to chronic renal disease, the process being accelerated by urinary tract infections. The aim of treatment is to restore as much as possible both essential functions: urine storage and timely emptying of the reservoir. What should and can be achieved is a more or less adequate, low-pressure, functional capacity of the bladder that is emptied as completely as possible by clean intermittent catheterization (CIC). MMC leads to the prototype of neurogenic bladder in childhood. What we know and what we do for MMC patients can roughly be applied to all other forms of neurogenic bladder, either congenital or acquired.

The story, described here in detail, started in 1962 with the publication of a seminal paper by Frederic Bartter et al. in the December issue of the American Journal of Medicine. The authors reported two pediatric patients with hitherto undescribed features, namely growth and developmental delay associated with hypokalemic alkalosis and normal blood pressure despite high aldosterone production. It soon became clear that this condition was not so exceptional. The syndrome named after Bartter was actually identified in children as well as in adults, females as well as males and in all five continents. It took almost four decades to clarify the exact nature of the disease. Bartter disease is an autosomal recessive disorder with four genotypes and mainly two phenotypes. Moreover, there are acquired secondary forms of Bartter syndrome as well as pseudo-Bartter syndromes. The history demonstrates the power of genetics but also illustrates the fundamental and irreplaceable contributions from nephrologists and renal physiologists.

Five patients with severe hemolytic uremic syndrome (HUS) were followed for 10-18 years. Because of proteinuria, arterial hypertension, and reduced glomerular filtration rates, they received either captopril (n=2) or enalapril (n=3), or both (n=1) for 8-15 years. Blood pressure was normalized and proteinuria reduced in all; glomerular filtration improved in three patients and fell moderately in two. Four of the five patients have reached adult age with body weight and height, blood pressure, and serum creatinine levels within the normal range. At the last evaluation, median proteinuria was 220 mg/24 h (range 0-310) and glomerular filtration rate 56 ml/min per 1.73 m(2)(range 40-127). This long-term study indicates a renoprotective effect of angiotensin-converting enzyme inhibitors in patients with sequelae after HUS.

Ten pediatric patients with Alport syndrome received enalapril for 5 years. There were nine boys. Eight patients have the X-linked form of the disease and two the autosomal recessive form. The median age at the start of treatment was 10.25 years. Only one patient was hypertensive. The starting dose of enalapril was 0.05 mg/kg; the target dose was 0.5 mg/kg per day. The median dose given effectively was 0.24, 0.37, 0.45, 0.43, and 0.49 mg/kg per day at years of study 1, 2, 3, 4, and 5, respectively. The median urinary protein/creatinine ratio was 1.58 g/g (range 0.49-4.60) before treatment. This decreased to 0.98, 1.09, 1.35, 1.11, and 1.38 g/g after 1, 2, 3, 4, and 5 years, respectively. The median creatinine clearance at baseline was 100 ml/min per 1.73 m2 (range 82-133) and after 5 years 92 ml/min per 1.73 m2 (range 22-115). Three patients did not reach the target dose of enalapril because of orthostatic hypotension. One of them was the only patient to develop chronic renal failure within 5 years. The present study indicates that enalapril reduces urinary protein excretion and preserves glomerular filtration in Alport patients as a group. However, there was individual variation, as in most studies of patients with proteinuric nephropathies given inhibitors of the angiotensin-converting enzyme.

A 5-year-old girl presented with short stature. She was found to have rickets due to renal phosphate wasting and nephrocalcinosis. Serum parathyroid hormone was suppressed, 25-OH vitamin D was within the normal range, and 1,25-(OH)(2 )vitamin D was elevated. In addition, she had hypercalciuria, proteinuria, which was partially tubular in origin, and a reduced glomerular filtration rate of 58 ml/min per 1.73 m(2). Treatment with phosphate supplements resulted in healing of the rickets and normalization of the serum 1,25-(OH)(2 )vitamin D level. This patient is an example of hypercalciuric rickets, most likely due to an inherited disorder of phosphate metabolism. Hypercalciuric rickets can be inherited as an autosomal recessive as well as autosomal dominant trait.

Twelve children and adolescents with classical Henoch-Schönlein purpura (HSP) underwent renal biopsy 2-9 years later. The clinical course was favorable in 10 of the patients who received only supportive treatment. Two patients with a prolonged course, characterized by marked hematuria and proteinuria, were given steroids and azathioprine first and mycophenolate mofetil later. At the time of biopsy, 4 patients did not have any urinary abnormalities, 6 had hematuria and/or mild proteinuria, and 2 had proteinuria >1 g/24 h. Renal histology showed mild lesions on light microscopy. Immunohistochemistry disclosed mesangial IgA in 8 of the 12 patients. In percentages, this is a proportion of 66.6 with 95% exact confidence limits of 34.9-90.1. In this small series of selected former HSP patients, the majority had IgA nephropathy years after the initial vasculitis episode. This indicates that some patients with apparently completely healed HSP have a chronic glomerular condition that possibly means protracted disease and certainly indicates the need for careful follow-up.

Growth of head circumference was studied along with height, weight, and body mass index (BMI) in 21 prepubertal patients with chronic renal failure (CRF) before and during recombinant human growth hormone (rhGH) treatment. CRF was present from birth in 15 patients, in the 6 others it was acquired and existing for at least 1 year. Five patients were on chronic dialysis, and 16 children were on conservative treatment with a median glomerular filtration rate of 17 ml/min per 1.73 m2 at the start of rhGH therapy. rhGH was administered for 12 months in all patients, for 18 months in 19, and for 24 months in 12 patients. Mean height standard deviation score (SDS) increased significantly from -2.29 to -1.31 after 1 year and to -1.07 after 2 years. Mean BMI SDS was within the normal range throughout. Mean head circumference SDS improved significantly from -2.04 to -1.45 after 1 year and remained stable thereafter. Changes in head circumference differed between patients under 5 years and those over 5 years. In the former, the increase in head circumference SDS was already significant after 6 months of therapy, in the latter, significance was reached only after 1 year. It can be concluded that rhGH in CRF patients significantly improves head circumference SDS, albeit not to the same extent as height SDS.

We aimed to assess the utility of the percentage of G cells and dysmorphic erythrocytes in the diagnosis of glomerular hematuria in pediatric patients. We determined the percentage of dysmorphic erythrocytes and G1 cells in urine samples from patients with glomerulonephritis and other renal diseases of non-glomerular origin. There was excellent correlation and agreement between results obtained by counting the cells in counting chambers and in urine sediments. With cut-off values of > or =1%, > or =2%, > or =5%, and 10% for G1 cells, sensitivities for the detection of glomerulonephritis were 62%, 40%, 28%, and 10% and specificities were 89%, 95%, 95%, and 98%. For the dysmorphic erythrocytes cut-off values of > or =10%, > or =20%, 50%, and > or =90% gave respective sensitivities of 95%, 95%, 93%, and 62% and specificities of 24%, 34%, 43%, and 85%. In 38% of cases of biopsy-proven glomerulonephritis no G1 cells were found. For cut-off values of > or =50% dysmorphic erythrocytes and > or =1% G1 cells, the sensitivity and specificity were 60% and 91%. For cut-off values of > or =50% dysmorphic or > or =1% G1 cells, sensitivity and specificity were 93% and 44%. Our results show that neither the percentage of dysmorphic erythrocytes nor the G1 cell count is of adequate sensitivity and specificity to enable reliable differentiation of glomerular and non-glomerular hematurias. Both tests are needed to achieve >90% sensitivity and specificity.

Fifteen children with chronic renal failure from early infancy who did not require renal replacement therapy were followed for 3 years. Chronic renal failure was defined as a serum creatinine at or above 1 mg/dl for the entire 1st year of life. These patients were treated conservatively with diet and supplements of sodium bicarbonate and sodium chloride, calcium and vitamin D. Erythropoietin was given to 5 patients. Neither nasogastric nor gastrostomy tube feeding was used, and none of the patients received recombinant human growth hormone. We analyzed length, weight, and head circumference at 3, 12, 24, and 36 months of age. All three variables displayed a significant drop in the first 3 months, but remained stable for the whole observation period thereafter. At the age of 3 years, the patients' mean values of length, weight, and head circumference standard deviation score were -1.96, -1.37, and -1.07, respectively. Height velocity during the 1st, 2nd, and 3rd year was 22.2, 10.9, and 7.6 cm per year, respectively. The first two figures and the cumulative height velocity are significantly better than those from a large cohort of chronic renal failure patients collected by the European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood; here the corresponding figures of height velocity were 12.3, 8.3, and 7.6 cm per year. Median serum calcium, phosphate, parathyroid hormone, and albumin levels remained within normal limits for the entire study period. Therapy-resistant hyperparathyroidism occurred in 1 patient and radiological signs of renal osteodystrophy in 4 patients. Kidney length, as measured by ultrasonography, showed almost no growth.

This baby boy was born after a pregnancy complicated by severe polyhydramnios at a gestational age of 28 weeks. Analysis of the amniotic fluid had shown a high chloride content, but normal concentrations of sodium, potassium, and calcium. After birth he displayed extreme polyuria, severe renal sodium and chloride loss, and marked hypercalciuria. Five weeks after birth, his sodium chloride loss turned into renal potassium loss, along with a marked decrease in urine output. All these features are characteristic of the neonatal variant of Bartter syndrome. He was discharged after 11 weeks with oral supplements of sodium chloride, potassium gluconate, and 500 ml of fluid. The follow-up for a period of 6 years showed a surprising evolution: he has no hypokalemic alkalosis, no polyuria, and no hypercalciuria; growth and development are within the normal ranges and, at the time of writing, he is a healthy boy needing no medication and with no medical problems whatsoever.

The effect of enalapril on urinary protein excretion and renal function was studied in six paediatric patients with various renal diseases causing nephroticrange proteinuria. In three younger children (aged 7-9 years) with steroid-resistant nephrotic syndrome, enalapril at a dose of 0.5 mg/kg per day given for 24 months yielded a temporary reduction of proteinuria in one child, a moderate and steady decrease in another and a complete disappearance of proteinuria in the third. Three adolescents, aged 17 years, took enalapril for 24 months at a dose of 20 mg/day. We observed no effect on proteiuria in one patient with Alport syndrome, a complete disappearance of urinary protein in one patient with membranoproliferative glomerulonephritis and a moderate decrease in the third patient who had idiopathic steroid-resistant nephrotic syndrome. Enalapril therapy resulted in an important reduction of proteinuria in two patients and a moderate decrease in three others. However this therapy was accompanied by a fall in glomerular filtration in all subjects, which was very marked in two patients. This fall in glomerular filtration may, however, simply reflect the natural course of the disease.

In 122 patients with the haemolytic uraemic syndrome (HUS), serum proteins were analysed in the acute phase of the disease (n = 122) and 6 weeks (n = 57) and 6 months (n = 84) later. Total serum protein levels were significantly lower on admission than 6 weeks and 6 months later (P < 0.0001). The same was true for median values of serum albumin (P < 0.0001), alpha 2-globulins (P < 0.0001) and gamma-globulins (P < 0.001). There was no difference in beta-globulins, whereas the alpha 1-globulins were significantly higher in the acute phase (P < 0.0001). There was a significant positive correlation between age and total protein and gamma-globulin levels. Serum total protein and albumin levels displayed a significant positive correlation with serum sodium levels and a significant negative correlation with urinary protein excretion. Patients with oligoanuria had significantly lower serum albumin and significantly higher alpha 1-globulin levels than those with preserved urine production. Marked differences were observed between patients with (D+) and patients without (D-) prodromal diarrhoea. In D(-) HUS, only albumin and total protein levels were lower on admission, but to a lesser degree than in D(+) HUS. Serum alpha 1-globulin levels were significantly higher and alpha 2-globulin levels significantly lower in D(+) HUS than D(-) HUS. In the D(+) subgroup of patients, by far the largest, there was a significant positive correlation between serum albumin and total protein on the one hand and the duration of the prodrome on the other.(ABSTRACT TRUNCATED AT 250 WORDS)

We measured serum levels of total and ionised calcium, phosphate, intact parathyroid hormone, 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D] and the vitamin D binding protein (DBP) in 14 children with idiopathic nephrotic syndrome and 10 healthy, age-matched controls. In all nephrotics serum DBP levels were below the normal range. Serum 25(OH)D was below 7 ng/ml in 10 of 14 nephrotic children and in the low normal range in the remaining 4 patients. The average serum 1,25(OH)2D levels were lower in the nephrotic patients than in the controls. However, free 1,25(OH)2D levels were normal in the nephrotic patients. Both serum 25(OH)D and 1,25(OH)2D correlated positively with the concentration of DBP. There was a significant negative correlation between serum DBP levels and the urinary protein excretion and a significant positive correlation between the urinary excretions of DBP and albumin. From this study it can be concluded that the nephrotic child is capable of maintaining appropriate serum concentrations of free calcitriol despite important urinary losses of both substrate and bound calcitriol.

Plasma renin activity (PRA) was measured in 50 consecutive patients (aged 4 months to 12 years) admitted during the acute phase of the haemolytic uraemic syndrome (HUS). Blood samples were taken as soon as the diagnosis was made and prior to any diuretic, anti-hypertensive or dialysis treatment. Prodromal diarrhoea was present in all but 3 patients, 17 were anuric and 12 were oliguric. PRA ranged from 0.3 to 24.2 ng/ml per hour and was low compared with values in normal infants and children: in 13 HUS patients PRA was above the median and in 37 it was below the median. PRA was significantly, independently and inversely related to age. There was no correlation, however, with blood pressure, urine output, volume status and serum levels of sodium, potassium and creatinine. Moreover, no relationship was found between PRA and the course of the disease. Our findings do not support the idea that renin activation plays a role in the pathophysiology of the haemolytic uraemic syndrome.

In three adolescents, suffering from membrano-proliferative glomerulonephritis type II, ophthalmoscopy and fluorescein angiography revealed retinal pigment epithelium lesions, referred to as basal laminar drusen. The patient with the longest renal history had the most pronounced fundus changes. These lesions, earlier described in adult patients, are believed to be specific for this particular form of chronic glomerulonephritis.

A 14-year-old boy presented with the clinical and radiological features of rickets. Serum inorganic phosphate levels were constantly low, whereas serum calcium and parathyroid hormone levels were within the normal range. Laboratory investigation did not show any evidence for vitamin-D deficiency, chronic renal insufficiency, Fanconi syndrome, tubular acidosis, hepatic disease or intestinal malabsorption. A family study comprising 34 members over four generations revealed 10 other individuals to be affected and the mode of inheritance to be autosomal dominant. In addition to hypophosphataemia and normocalcaemia, the disease is characterized by elevated serum 1,25 dihydroxyvitamin D levels and hypercalciuria. This hereditary syndrome of renal hypophosphataemia differs from the common familial X-linked hypophosphataemia and the recently described autosomal recessive hypophosphataemic rickets with hypercalciuria by its dominant mode of inheritance; it differs from hypophosphataemic non-rachitic bone disease by the elevated serum 1,25 dihydroxyvitamin D levels and hypercalciuria.

A boy with sparse red hair, absent eyebrows and eyelashes, cutaneous telangiectasia, poorly developed subcutaneous fat and normocomplementaemic membranoproliferative glomerulonephritis is described. Additional findings were an old-looking, peculiar face, mild developmental delay, calcified choroid plexus and renal arteriolosclerosis. It is believed that this is a new case of a newly recognized entity.

Growth from birth to the age of 19 years was studied in a patient with the neonatal form of Bartter syndrome. The initial modes of therapy (extra fluid, potassium supplements and triamterene) resulted in satisfactory but not optimal growth. Treatment with spironolactone together with potassium led to impressive catch-up growth. When the patient reached the age of 9 years, indomethacin therapy was started, which resulted in a second growth acceleration and was also accompanied by a significant reduction of both polyuria and hypercalciuria. Puberty developed normally, menarche occurred at 12 years 4 months and a normal adult height of 162 cm was reached at the age of 14 years. Treatment with prostaglandin synthetase inhibitors seems to be the best therapy for children with the neonatal form of Bartter syndrome.