The best game is the waiting game.

Chronic dialysis and renal transplantation have been developed over the last three decades of the 20th century. These two forms of renal replacement therapy have revolutionized the fate of children in established renal failure. Yet, chronic dialysis is a serious burden to both the patient and the family and the long-term results of renal transplantation are far from excellent. Moreover, both forms of treatment have serious complications, some of them fatal. It is therefore important to highlight what has been achieved in terms of conservative treatment of chronic renal failure. This paper describes in detail the progress made in this field with special emphasis on the great opportunity to slow down progression from chronic renal disease to end-stage renal failure. Renal replacement therapy can wait in many children and should be postponed as long as possible, ideally until they have reached adulthood.

Autosomal dominant polycystic kidney disease in the neonatal period: association with a cerebral arteriovenous malformation.

Two brothers with the neonatal presentation of dominant polycystic kidney disease are reported. The first infant died shortly after birth; autopsy revealed polycystic kidneys. The second infant had two markedly enlarged kidneys at birth. Intravenous pyelography at the age of 10 days showed typical images as observed in the recessive form of polycystic kidney disease. Kidney biopsy showed cystic dilation involving all parts of the nephron; the liver biopsy did not show any abnormality. Severe arterial hypertension was a major problem in the first six months of life. At the age of 3 and 5 years, respectively, the patient developed intracerebral hemorrhage, which was due to a complex intracerebral arteriovenous malformation. At the age of 8 years the boy had chronic renal failure and spastic quadriplegia. Previously unsuspected polycystic kidneys were found in the father during the family study.

Recombinant human erythropoietin increases blood pressure, platelet aggregability and platelet free calcium mobilisation in uraemic children: a possible link?

Recombinant human erythropoietin was administered to 10 uraemic children on chronic haemodialysis, all of whom responded by correcting their haemoglobin. In addition, they showed an increase in blood pressure; platelet aggregations, subnormal before therapy, improved during treatment. The intracellular free calcium concentration in platelets after thrombin stimulation also increased significantly during erythropoietin administration. We hypothesize that the effect of erythropoietin on platelet aggregability and on blood pressure may be due to an increase in the intracellular free calcium mobilisation in platelets and possibly in smooth muscle cells respectively.

Diaphragmatic hernia in Denys-Drash syndrome.

We report on a newborn infant with male pseudohermaphroditism and glomerular lesions (Denys-Drash syndrome) but without Wilms tumor. A constitutional heterozygous mutation in the WT1 gene (366Arg to His) was identified. In addition the child had a large diaphragmatic hernia, so far not described in Denys-Drash syndrome. The expression of the WT1 gene in pleural and abdominal mesothelium and the occurrence of diaphragmatic hernia in transgenic mice with a homozygous WT1 deletion strongly suggests that the diaphragmatic hernia in this patient is part of the malformation pattern caused by WT1 mutations.

Prostacyclin production by whole blood from children: impairment in the hemolytic uremic syndrome and excessive formation in chronic renal failure.

The capacity of leukocytes to produce prostacyclin (PGI2) from endogenous and from platelet-derived endoperoxides was tested in whole blood. During the acute phase of the hemolytic uremic syndrome (H.U.S.), the PGI2-production was lower than the controls, whereas the blood from children with chronic renal failure produced higher amounts. Production of PGI2 by blood from children 3/12 to 6 years after the acute phase of H.U.S. was normal, as was the case with blood from their parents. Furthermore, in two H.U.S.-patients studied serially, the decreased PGI2-production capacity normalized 2 1/2 months after the acute phase.

Calcium and phosphorus retention in the preterm infant during total parenteral nutrition. A comparative randomised study between organic and inorganic phosphate as a source of phosphorus.

The preterm infant fed parenterally is prone to some demineralisation due in part to insufficient Calcium (Ca) and Phosphorus (P) retention. In an attempt to augment Ca and P retention, we prepared a standardised parenteral solution containing calcium gluconate and glucose-1-phosphate (Phocytan) as source of phosphorus, yielding a daily supply of 75 mg/kg Ca and 45 mg/kg P. 28 very low birthweight infants were randomly assigned to receive either this solution (high Ca P ; n = 15) or a conventional formulation containing calcium gluconate and potassium mono- and dibasic phosphate delivering 42 mg/kg Ca and 36 mg/kg P daily (low Ca P ; n = 13). In the high Ca P daily retention was respectively 80% and 99% for Ca and P whereas in the low Ca P group, retention was 70% and 82%. Serum parathormone levels were significantly lower in the high Ca P group. We conclude that parenteral nutrition with a new high Ca P supplement results in an augmented Ca and P retention in very low birthweight infants. This may help to prevent neonatal bone demineralization.

Head circumference in chronic renal failure from birth.

AIMS: Chronic renal failure in childhood jeopardizes both growth and development. In children with chronic renal failure from birth, growth in height and weight have been found to be generally poor. Few data on head circumference are available. MATERIAL: A cohort of 19 children with chronic renal failure from birth was studied from the early weeks of life to the age of 5 years. There were 18 boys; and 18 patients had congenital renal hypoplasia or hypodysplasia associated with obstructive uropathies. Eight patients received recombinant growth hormone (rhGH) after the age of 2 years. Only 2 patients needed renal replacement therapy before the age of 5 years. Data after transplantation were not included. METHODS: The following variables were analyzed: body height, body mass index and head circumference. Data were expressed in median values of standard deviations scores (SDS). RESULTS: In the first 3 months of life there was a significant drop in height SDS, body mass index SDS and head circumference SDS. Thereafter, a stable growth velocity was observed for the rest of the study period, except for body mass index SDS. which improved after 36 months. There was a striking difference between patients who needed treatment or not with recombinant human growth hormone (rhGH). Patients without rhGH displayed a stable growth after the age of 3 months until 5 years of age. In the remaining 8 patients, rhGH treatment resulted in a significant increase not only in height SDS but also in head circumference SDS. CONCLUSIONS: In infants and young children with chronic renal failure from birth, growth in head circumference parallels growth in body height. This applies to all patients and to data before and during rhGH treatment.

Hemolytic uremic syndrome in childhood: renal function ten years later.

Forty-six patients who developed a Hemolytic Uremic Syndrome (HUS) during the period 1970-1976, were examined ten years later. Thirty-two individuals had no signs of renal disease whereas fourteen showed at least one abnormality. In the latter group a urinary osmolality below 800 mosmole per kg water was the most frequent defect found (eight cases). Three adolescents had both hypertension and proteinuria, which are considered as important late sequelae.

Nephropathic cystinosis: effect of long-term cysteamine therapy.

Three children with nephropathic cystinosis received cysteamine therapy, mostly in the form of phosphocysteamine, for more than six years. The patients were between two and three years of age at the start of the study. The daily dose of cysteamine was 60 mg/kg as cysteamine base. In all three, rapidly progressive renal failure occurred before their 10th birthday. When comparing their evolution with data on the natural history of childhood cystinosis, no improvement was observed in terms of growth and glomerular function. It is concluded that cysteamine therapy did not provide clear benefit to the three patients reported here.

Nephronophthisis and tapetoretinal degeneration associated with liver fibrosis.

A 12 year-old boy was referred because of general weakness, enuresis and pallor which had been present for at least six months. Previously, the child had been hospitalized at the age of five, because of mental retardation and hepatosplenomegaly, for which no cause could be found. He had severe renal insufficiency, with all the hallmarks of nephronophthisis. In addition his vision was very poor and fundoscopy revealed tapetoretinal degeneration. The liver and spleen were grossly enlarged. Liver function was almost completely normal, but histology showed diffuse periportal febrosis with profiferation of the bile ducts. This observation seems to confirm the existence of a new syndrome, associating nephronophthisis and liver fibrosis as described by Boichis and coworkers (1973).

Ultrasonography for assessment of bleeding after percutaneous renal biopsy in children.

Ultrasonography has been used to assess renal bleeding after percutaneous renal biopsy in 57 infants and children. A perirenal hematoma was found in 10 patients i.e. an incidence of 16 per cent. An additional patient with heavy hematuria and temporary obstruction of the pelvis due to clot formation had an enlarged kidney and pelvicalyceal dilatation on ultrasound examination. We did not find a correlation between the clinical findings, the fall in hematocrit and the presence of a hematoma. Ultrasound can be regarded as the method of choice for monitoring renal bleeding in children who have undergone kidney biopsy.

Abnormal prostacyclin metabolism in the hemolytic uremic syndrome: equivocal effect of prostacyclin infusions.

In a child with the hemolytic uremic syndrome, plasma 6 keto-prostaglandin F1 alpha levels remained undetectable throughout the acute phase of the disease. The patient's plasma failed to stimulate prostacyclin production by "exhausted" rat aorta rings. In vitro study of the patient's vessels indicated that they retained the capacity to synthesize prostacyclin from exogenous arachidonic acid but that their endogenous arachidonic acid stores were either depleted or non-available. The response to repeated infusion of exogenous prostacyclin was equivocal, suggesting that abnormal prostacyclin metabolism in the hemolytic uremic syndrome may not be the only factor in its pathogenesis.

Reversible arterial spasm in an adolescent with primary oxalosis.

A 16-year-old girl with primary oxalosis type I presented with progressive claudication soon after being treated with chronic intermittent hemodialysis. Arterial insufficiency of the lower limbs was confirmed clinically (purple discoloration of the skin and absence of arterial pulses) and with Doppler sonography. The arteriogram showed diffuse and symmetric narrowing with smooth vessel walls. Treatment with sodium nitroprusside had a spectacular effect; nifedipine was less effective. Renal transplantation with the father's kidney resulted in a rapid, complete and sustained reversal of the ischemic features. Magnesium withdrawal is assumed to be a pathogenic factor of the vascular spasm in this patient.

Recurrent acute renal failure due to nonaccidental poisoning with glafenin in a child.

A 7-year-old boy experienced recurrent attacks of acute renal failure over an 18 month period. Each attack was accompanied by a fluorescent yellow discoloration of his urine. Laboratory data and the kidney biopsy were consistent with acute tubulo-interstitial nephritis. Repeated contacts with the boy in a play setting and thorough toxicologic examination of his urine finally led to the conclusion that the mother systematically poisoned her child with glafenin. The clinical and experimental literature on glafenin-related disease is reviewed. This is the first report of glafenin intoxication in a child. This is also the first case of kidney disease as an expression of child abuse.

The complement system in hemolytic-uremic syndrome in childhood.

A dynamic estimation of the complement system was obtained by immunochemical estimation of C3, C4, C5, C1q, C3b + C3c, C3d, Ba in children with hemolytic-uremic syndrome. The presence of increased breakdown products of C3 (C3b + C3c, C3d) and of factor B (Ba) suggests an activation of the complement system possibly by the alternative pathway. No definite explanation for these complement abnormalities can be given.

Renal transplantation in 20 children with hemolytic-uremic syndrome.

In this study the outcome of kidney transplantation in 20 patients with end-stage renal disease (ESRD) due to the hemolytic uremic syndrome (HUS) was evaluated. The characteristics and severity of the primary disease in these patients were not different from those commonly reported in patients with HUS. Eleven children developed ESRD immediately following HUS, in nine others temporary partial recovery of kidney function for 0.5-13.2 years was observed. Twenty-four grafts were transplanted in these 20 patients. Graft survival was no different from overall cadaver graft survival. In nine patients failure of the first kidney graft occurred, while the four second grafts were still functioning at the time of writing. Recurrence of HUS was suspected but not proven to be the cause of first graft failure in two patients, and impaired graft function in a third one. A short interval between HUS and kidney transplantation seems to adversely affect graft survival. No other factors influencing outcome of transplantation could be detected.

Surgical correction of vesicoureteral reflux: 5-year follow-up with 99Tcm-DMSA scintigraphy.

AIM: To evaluate kidney function before and after surgical correction of vesicoureteral reflux. The long-term effect was measured with quantitative nephro-scintigraphy using 99Tcm labelled dimercaptosuccinic acid (99Tcm-DMSA). METHODS: Forty-five children with a history of urinary tract infections due to vesicoureteral reflux (VUR) were studied. VUR grade was determined with contrast voiding cystourethrography. Planar scintigraphy was performed with 99Tcm-DMSA and uptake measured as a percentage of injected dose. Kidney function was evaluated at baseline and 5 years after corrective surgery. RESULTS: Three months after surgery, persistent mild reflux was found in eight of 76 treated renal units. Kidney uptake at 5-year follow-up was unchanged in the majority of children, indicating preservation of renal function found at baseline. The split renal function showed an excellent correlation (r = 0.99) between baseline and follow-up studies (regression slope 1.01). Percentage uptake had a regression slope of 0.89 significantly different from unity (P<0.05). Empirical kidney-depth correction techniques were compared. The scintigraphic pattern worsened in six kidneys, indicative of increased scarring in a minority of children. CONCLUSION: Planar nephro-scintigraphy with 99Tcm-DMSA was well tolerated in our paediatric population, and appeared appropriate to evaluate kidney function in time. After surgical correction of VUR, the baseline function was maintained in 94% of kidneys.

Prenatal indomethacin toxicity in one member of monozygous twins; a case report.

A mother, treated with indomethacin because of premature labour, delivered a pair of monozygous twins at a gestational age of 33 weeks. Because of foetal transfusion syndrome, the first twin was polycythaemic and the second anaemic. The latter was also hydropic, suffered from anuria requiring peritoneal dialysis, and showed signs of severe pulmonary hypertension, probably as a consequence of intra-uterine constriction of the ductus arteriosus. The possible interaction between foetal transfusion syndrome, anuria, premature constriction of the ductus arteriosus and the prenatal administration of indomethacin is discussed. In general, indomethacin should cautiously be used as a tocolytic agent.

Electrolyte composition of the amniotic fluid in Bartter syndrome.

In three patients with neonatal Bartter syndrome associated with polyhydramnios, analysis of the amniotic fluid showed normal sodium, normal-to-low potassium, but high chloride concentrations. This finding clearly suggests a renal chloride reabsorption defect as the primary cause of the neonatal form of Bartter syndrome. It is suggested that whenever polyhydramnios occurs, the electrolyte composition of the amniotic fluid should first be analysed in order to establish the diagnosis of Bartter syndrome.

[The neonatal form of Bartter's syndrome: current findings in etiology and physiopathology]. / De neonatale vorm van het syndroom van Bartter: nieuwe inzichten in etiologie en fysiopathologie.

I. Time has come to distinguish "Bartter syndrome" from "Bartter disease". The latter is an autosomal recessive renal tubulopathy which manifests itself mostly during infancy and childhood. II. Bartter disease is caused neither by a primary renal potassium loss nor by a primary renal hyperprostaglandinism. All evidence is in favor of a defect in the chloride pump located at the thick ascending limb of Henle's loop. III. The most severe expression of Bartter disease is its neonatal form which is characterized by polyhydramnios, premature delivery and a life threatening sodium chloride loss during the early weeks of life. It takes several weeks before sodium wasting turns into renal potassium wasting. IV. Polyhydramnios not associated with echographically detectable fetal malformation is highly suggestive of Bartter disease. Prenatal diagnosis is based on the combination of fetal polyuria and elevated chloride in the amniotic fluid. V. In this setting the administration of indomethacin is useless and even dangerous from the 32nd week of gestation on. Similarly, indomethacin should not be given to the newborn Bartter patient for the first weeks and months of life. Treatment at that stage consist mainly of the administration of large amounts of fluid and sodium chloride. VI. Indomethacin can be used as soon as children with Bartter disease stop growing normally and preferably after the age of 18 months when kidney maturation is established. The daily dose should not exceed 2.5 mg/kg body weight. VII. Hypercalciuria is part of (the neonatal form of) Bartter disease and it is so severe that nephrocalcinosis seems to be the rule. This hypercalciuria is the direct consequence of the chloride reabsorption defect in Henle's loop. Research is needed to find an adequate solution to this problem.