[Neurogenic bladder function disorders in patients with meningomyelocele: S2k guidelines on diagnostics and therapy]. / Neurogene Blasenfunktionsstörungen bei Patienten mit Meningomyelozele : S2k-Leitlinie zu Diagnostik und Therapie.

The treatment of children and adolescents with meningomyelocele has experienced a clear change in the last 30 years. The establishment of pharmacotherapy, clean intermittent catheterization (CIC) and infection prophylaxis have improved the prognosis for patients and have led to new therapeutic strategies. The interdisciplinary cooperation between neonatologists, neurosurgeons, pediatric neurologists, pediatric urologists, pediatric nephrologists, pediatric orthopedists and pediatric surgeons leads to optimization of individualized therapy. These guidelines present definitions and classifications, investigations and timing which are described in detail. The conservative and operative therapy options for neurogenic bladder function disorders are described and discussed with reference to the current literature. The brief overview provides in each case assistance for the treating physician in the care of this patient group and facilitates the interdisciplinary cooperation.

[Urinary tract infections in infants and children -- a consensus on diagnostic, therapy and prophylaxis]. / Harnwegsinfektionen im Säuglings- und Kindesalter. Konsensusempfehlungen zu Diagnostik, Therapie und Prophylaxe.

Urinary tract infections (UTI) are among the most common bacterial infections in infants and children. The early diagnosis of a pyelonephritis and its rapid, calculated antibacterial therapy are decisive for the prognosis. Urogenital anomalies, renal damage and bladder dysfunction may influence the risk of recurrences of UTI and pyelonephritic scarring. Diagnostic strategies therefore should focus on their early recognition. Pediatricians, urologists and infectiologists are cooperating in diagnostic, therapy and prophylaxis of UTI. The aim of the interdisciplinary consensus presented was to work out a concept which may help to manage childhood UTI in daily practice.

Recessive missense mutations in LAMB2 expand the clinical spectrum of LAMB2-associated disorders.

Congenital nephrotic syndrome is clinically and genetically heterogeneous. The majority of cases can be attributed to mutations in the genes NPHS1, NPHS2, and WT1. By homozygosity mapping in a consanguineous family with isolated congenital nephrotic syndrome, we identified a potential candidate region on chromosome 3p. The LAMB2 gene, which was recently reported as mutated in Pierson syndrome (microcoria-congenital nephrosis syndrome; OMIM #609049), was located in the linkage interval. Sequencing of all coding exons of LAMB2 revealed a novel homozygous missense mutation (R246Q) in both affected children. A different mutation at this codon (R246W), which is highly conserved through evolution, has recently been reported as causing Pierson syndrome. Subsequent LAMB2 mutational screening in six additional families with congenital nephrotic syndrome revealed compound heterozygosity for two novel missense mutations in one family with additional nonspecific ocular anomalies. These findings demonstrate that the spectrum of LAMB2-associated disorders is broader than previously anticipated and includes congenital nephrotic syndrome without eye anomalies or with minor ocular changes different from those observed in Pierson syndrome. This phenotypic variability likely reflects specific genotypes. We conclude that mutational analysis in LAMB2 should be considered in congenital nephrotic syndrome, if no mutations are found in NPHS1, NPHS2, or WT1.

[Fetal nephro-/uropathy: a retrospective analysis of 124 cases seen in the period from 1996 to 2002]. / Fetale Nephro-/Uropathien: Retrospektive Analyse von 124 Fällen, erfasst im Zeitraum von 1996 bis 2002.

BACKGROUND: The embryological development of the kidneys and the urinary tract follows a complex choreography. Disorders are quite common. The incidence of disorders amounts to 0.3 - 0.8 % of live-born infants. In addition, several chromosomal anomalies are combined with renal malformations. The poor prognosis of some of these diseases is reflected in a perinatal mortality of 6.3 %. PATIENTS AND METHODS: Retrospectively 124 cases with fetal nephro-/uropathy detected by prenatal ultrasonography between 1996 and 2002 were analyzed. Features of hypo-dysplastic kidneys (uni- or bilateral) were seen in 21 cases. Multicystic kidney disease (uni- or bilateral) existed in 40 fetuses. In some cases of multicystic or dysplastic kidney diseases, extrarenal malformations were combined. 21 fetuses suffered from autosomal recessive polycystic kidney disease. 18 male unborns showed the typical picture of intravesical obstruction due to posterior uretheral valves. The prune belly syndrome was seen 4 times. Hydronephrotic kidneys with more than 5 mm pelvic dilatation were detected in 13 cases. Renal agenesis led to a lethal outcome perinatally in 5 cases. One child died of bilateral thrombosis of renal artery and venous system. RESULTS: The high incidence of diseases with a poor prognosis accounts for the high mortality of 50.8 % (intrauterine or postnatal death, induced abortion). Such a fatal outcome was observed in autosomal recessive polycystic kidney disease, bilateral multicystic dysplastic kidney disease, bilateral renal dysplasia combined with severe extrarenal malformations, intravesical obstruction, renal agenesis and bilateral thrombosis of the renal vessels. Only 60 children survived. Of these 26 needed urological surgery. 15 suffered from progressive renal insufficiency. During a follow-up of 8 - 58 months only 44 exhibited a normal renal function. CONCLUSIONS: Such complex renal and urological diseases in the fetus require an interdisciplinary management of the pregnancy.

[Complex malformation: cake kidney with concomitant sacral agenesis]. / Komplexe Malformation: Kuchenniere und begleitende sakrale Agenesie.

Ectopic kidneys are frequently associated with primary renal dysplasia or a disturbance of urine transport. Sacral agenesis is defined by the absence of two or more bodies of the lower vertebral and is often associated with a neurogenic bladder dysfunction. A 5-year-old boy with sacral agenesis and a right-sided cake kidney, presented with progredient renal failure caused by recurrent urinary tract infections, incomplete bladder emptying and vesicorenal reflux. After extensive diagnostics, the anatomical situation was explored by laparotomy to find a solution for this complex situation. Despite modern diagnostic tools, the preoperatively estimated renal function of the cake kidney was incorrect. After resecting of the right collecting system and refluxing megaureter out of the cake kidney, anti-refluxive implantation of the left ureter into the bladder was performed and the megacystis was treated by detrusor duplication. After three years, the now 8-year-old boy voids residual free without any signs of urinary tract infection. Renal function and proteinuria have improved. The only medication required is nifedipine (20 mg twice a day) for treatment of the renal hypertension.

Familial hypomagnesemia-hypercalciuria in 2 siblings.

Familial hypomagnesemia-hypercalciuria with nephrocalcinosis and renal insufficiency in childhood is a rarely described disease. Two siblings of consanguineous Tunesian parents (first cousins), a 2-year-old boy and a 4-year-old girl presented with renal insufficiency and severe bilateral nephrocalcinosis. Both were found to have decreased serum and intracellular magnesium concentrations, increased urinary excretion of magnesium and calcium, mild glomerular and severe tubular proteinuria and low citrate excretion in urine. Pathological biochemical findings and the severity of nephrocalcinosis of the boy compared to findings of the sister were strongly marked, Histology of the boy's kidney showed severe medullary nephrocalcinosis, tubular atrophy, focal lymphoplasmacellulary infiltration, focal cortical fibrosis, immature glomerula, segmental and global glomerulosclerosis. Subsequent mutation analysis revealed a homozygous frameshift mutation in the gene paracellin-1 in both affected individuals. Therapy consisted of sodium bicarbonate, cholecalciferol, calcitriol, hydrochlorothiazide, citrate salts and oral magnesium administration. Hypercalciuria decreased in both children by therapy with thiazide diuretics, but hypomagnesemia was unresponsive to magnesium administration. After a 32-month follow-up the boy commenced hemodialysis at the age of 5 years, whereas his sister showed no decline in renal function.

Extracorporeal shock wave lithotripsy in children. Efficacy, complications and long-term follow-up.

OBJECTIVES: Extracorporeal shock wave lithotripsy (ESWL) is effective and safe for the treatment of upper urinary tract calculi in adults. Some speculations concerning possible damages from ESWL on the growing kidney have been raised. METHODS: From January 1990 to December 1998, 64 children (30 girls and 34 boys; 8 months to 15 years old, mean 5.6 years) with a total of 83 stones of the upper urinary tract were treated by ESWL (Lithostar). Preoperative evaluation included history, physical examination, routine blood tests, urinalysis, urine culture, intravenous urography and optional renal scintigraphy. The impulse rate per treatment varied from 750 to 4,000 (mean 2,996). After acute treatment, routine follow-up included renal ultrasound, blood pressure controls, laboratory tests and eventually plain film X-ray. RESULTS: Successful fragmentation of the stones was achieved in all patients. In 54% the patients were free of stones treated at the time of discharge. At 3 months after treatment radiographic studies showed no residual fragments in 80% of the treated children. 83% of the treated stones were cleared entirely. The remaining fragments were clinically insignificant. An average of 2.5 ESWL treatments per child in general anesthesia were required. Stone analysis showed 20 calcium oxalate, 38 calcium phosphate, 12 struvite, 2 uric acid and 9 cystine calculi. Ureteral stents were placed in 43%. No significant urinary infection was seen under antibiotic prophylaxis. Only 3 children showed a recurrence (1 x cystinuria with low compliance and 2 x struvite). There was no case of renal scarring. No change in renal function or blood pressure was found compared to the preoperative values. Hematuria and proteinuria disappeared in all children who were free of stones. Renal ultrasound revealed no growth difference between treated and untreated renal units. CONCLUSIONS: In childhood, ESWL is an efficacious and safe treatment of stones of the upper urinary tract. The long-term follow-up after ESWL with a second-generation lithotriptor did not show any signs of damage to the growing kidney. Sometimes repeated ESWL treatments are justified by the low rate of complications.

Central nervous system involvement in hemolytic uremic syndrome (HUS)--a retrospective analysis of cerebral CT and MRI studies.

PURPOSE: To evaluate the morphological changes of cerebral involvement in children with HUS utilizing CT and MRI. METHOD AND PATIENTS: We retrospectively analyzed 13 cranial CTs (CCT) and 3 cranial MRI studies of 5 out of 93 patients with clinically proven HUS and severe CNS involvement (seizures and coma and dysregulation of breathing) referred to the department of pediatric nephrology (aged 1.5-15 years, median 2 years, 2 girls, 3 boys) between 1987-2000. RESULTS: Three of 5 patients had CT and MRI studies, 2 patients had CT scans only. One of 2 patients with isolated basal ganglia ischemia and normal first CCT developed a secondary hemorrhagic infarction. Another patient with an initially normal MRI developed an infarction of the right cerebral arteries with mass effects. One of 2 patients with basal ganglia involvement showed additional infarction of thalami and external and internal capsules whereas the other had only minimal involvement of adjacent white matter, but consecutive hemorrhagic infarction. Four of 5 children died (3 of them with varying extents of basal ganglia and adjacent white matter involvement, 1 with right cerebral artery infarction). Basal ganglia involvement was found in the majority of cases as well as in all lethal cases. The surviving patient with isolated basal ganglia involvement now suffers from tetraspastic disorder and convulsions. CONCLUSION: Cerebral involvement is one of the major complications of HUS. According to the literature, basal ganglia involvement in HUS is common and quite often associated with other cerebral pathologies. First imaging findings may not show pathologies. Contradictory to previous reports, even children with isolated basal ganglia pathology and/or less involvement of white matter and coma may either die from the underlying disease or their clinical outcome may be poor.

Renal Fanconi syndrome: first sign of partial respiratory chain complex IV deficiency.

A 2-year-old boy who developed hypophosphatemic rickets without signs of muscular weakness or neurological disturbances is presented. Biochemical findings included hypophosphatemia, metabolic acidosis, hypouricemia, hyperphosphaturia, severe glucosuria, generalized hyperaminoaciduria, hypercalciuria, proteinuria with elevated excretion of IgG, transferrin, albumin and high levels of alpha-1-microglobulin. Urine concentration capacity and creatinine clearance were normal. Lactaturia without elevated levels of plasma lactate and a high urinary excretion of beta-hydroxybutyrate were suggestive for mitochondriopathy. Partial deficiency of cytochrome c oxidase (complex IV of the respiratory chain) was found in skeletal muscle. A renal biopsy specimen demonstrated enlarged mitochondria with abnormal arborization and disorientation of the cristae in the proximal tubular cells. Reduced activity of mitochondrial cytochrome c oxidase in tubular cells could be demonstrated by ultracytochemistry. In conclusion, rickets due to the renal Fanconi syndrome can be the first clinical sign of mitochondrial cytopathies without extra-renal symptoms. Elevated excretion of lactate and ketone bodies in urine may serve as a diagnostic marker.

[Retinitis pigmentosa, terminal renal insufficiency and Caroli syndrome: new associations with Opitz trigonocephaly syndrome]. / Retinitis pigmentosa, terminale Niereninsuffizienz und Caroli-Syndrom: neue Assoziationen zum Opitz-Trigonocephalie-Syndrom.

We report on a new patient with Opitz trigonocephaly syndrome. In addition to the findings typical of this mental retardation syndrome, the present patient has retinitis pigmentosa, Caroli's syndrome and renal failure, which is undergoing hemodialysis. This association is never observed before in patients with Opitz trigonocephaly syndrome. This case demonstrate, that with increased survival of patients with mental retardation syndromes, the phenotypes possible are modified.

Spectrum of early onset nephrotic syndrome associated with WT1 missense mutations.

We investigated 17 children with nephrotic syndrome (NS) of early onset (14 aged < 1 year) and rapid progression to end-stage renal disease for the presence of mutations in the Wilms' tumor suppressor gene WT1 on chromosome 11. In eight children (7 genotypic males) an association with Wilms' tumor and/or ambiguous genitalia (Denys-Drash syndrome) was observed. In these eight and two additional female patients with NS only constitutional missense mutations in the WT1 gene were detected; four children presented the so-called hot spot mutation in exon 9 (R394N) and six had different mutations in exons 8 and 9 (4 not previously described). Renal biopsy showed diffuse mesangial sclerosis in eight and focal segmental sclerosis in two cases. End-stage renal disease was reached either concomitantly or within four months after onset of NS in seven of ten patients. A unilateral Wilms' tumor was found before or concomitant with NS in four children (3 males, 1 female). From the seven genotypic males with WT1 mutations, five presented ambiguous genitalia and two a female phenotype. No mutation of the WT1 gene was found in seven other children with isolated congenital or infantile NS with or without DMS who appeared to have a slower progression than the first group. It is proposed that patients with early onset, rapidly progressive NS and diffuse mesangial or focal segmental sclerosis should be tested for WT1 mutations to identify those at risk for developing Wilms' tumor.

The addition of aminoacids and phosphate to hemodiafiltration solutions in newborns with hyperammonemic coma.

A child with carbamyl-phosphate-synthetase defect who died after prolonged continuous hemodiafiltration in deep coma proved to have high aminoacid losses despite aminoacid infusion. We think that this results from high small-solute clearance during hemodialysis. In order to prevent these inevitable catabolic side-effects we decided to add aminoacids to the dialysate and substitution fluid in these children with metabolic diseases. Additionally we propose to add phosphate in order to avoid depletion. The aim is to achieve anabolic or at least non-catabolic hemodiafiltration.

[Interdisciplinary management of fetal obstructive uropathy]. / Das interdisziplinäre Management der fetalen obstruktiven Uropathie. Zwei Fallbeispiele.

The joint care of children with obstructive uropathy by perinatologists, pediatric intensivists, pediatric nephrologists and urologists can preserve as much renal function as possible. Complications such as urinary tract infections and problems with renal insufficiency can be prevented. Preterm delivery for early surgical decompression of the urinary tract postpartal should be performed only in exceptional cases. We want to underline that supporting and counselling parents in coping with severe findings and prognosis of the disease is among our main aims. We will present two selected cases to demonstrate the spectrum of methods for handling fetal obstructive uropathy.

[Management of children with prenatally diagnosed urinary tract abnormalities]. / Betreuung von Kindern mit pränatal diagnostizierten Harnwegfehlbildungen.

Between 1984 and 1991, antenatal ultrasound scanning detected urinary tract malformations in 126 infants, who were investigated and treated postnatally in the childrens' hospital of the Westfälische Wilhelms-University Münster. 10 out of 126 children with urogenital changes, died in the first hours after birth, due to pulmonary hypoplasia (Potter's sequence), 1 further infant died later after cardiac operation, and another died of megacystic-megaureter-hypoperistaltic-syndrome. In the first months after birth 71 (61%) of 116 infants underwent urological surgery; 12/116 infants (10.3%) had severe bilateral kidney changes, some of them with severe deficiency of amniotic fluid before birth. 6/116 infants (5.2%) had chronic renal insufficiency, 2 of them will have to be dialyzed in early childhood and longterm, 14 patients (12%) are threatened by chronic renal failure. 14 patients (12%) developed severe arterial hypertension, all had to be treated with antihypertensive drugs, in 5 of them hypertension subsided after unilateral nephrectomy, another five had transient hypertension, but four require continued medical treatment. We describe the prenatal ultrasound findings, compared them with diagnosis after birth, illustrate diagnostics, plans of therapy, urological surgical interventions and nephrological consequences. Benefits and limitations of antenatal ultrasonography for the detection of urinary tract malformations and the treatment of those malformations before and after birth are discussed. In utero diagnosis of severe urinary tract abnormalities allows treatment of these infants immediately after birth, furthermore the prevention of severe infections, additional damage of renal tissue, and early diagnosis and treatment of arterial hypertension and metabolic imbalances caused by chronic renal insufficiency in early childhood.

[Arterial hypertension. Prevention in infants with congenital urinary tract malformations]. / Arterielle Hypertonie. Vorkommen bei Säuglingen mit angeborener Fehlbildung der ableitenden Harnwege.

Eighty-nine newborns and infants with congenital urinary tract malformations were treated in the childrens' hospital of the Westfälische Wilhelms-University from 1986 to 1989. Twenty patients of this group (22.5%) developed severe hypertension requiring treatment within the first year of life. Mean age of diagnosis of hypertension was 5 months (range 0.5-12 months). Median values for blood pressure at time of diagnosis were 138 mmHg (range 120-170) for systolic and 92 mmHg (range 80-110) for diastolic values. Six patients showed characteristic symptoms for hypertension such as restlessness, sweating and sleep disorders. Plasma levels of renin were obtained in 12 of 20 patients. Five patients had raised plasma renin levels. All patients with a severe hypertension were treated with one to several antihypertensive drugs. Risk factors for the development of severe renal hypertension in early infancy are cystic renal malformation, vesico-ureteral reflux, obstructive uropathy and to our experience also short term percutaneous nephrostomy in obstructive uropathy in particular in connection with pyelonephritis. Hypertension can still appear after the successful surgical correction of urinary obstruction. We describe the group of patients with severe hypertension in our study group; diagnostic principles and our therapeutic approach are explained. We conclude that early diagnosis of severe hypertension and consecutive treatment are important in infants with congenital urinary malformations.

[Autosomal dominant polycystic kidney disease in infancy]. / Autosomal dominante polyzystische Nierenerkrankung im Säuglingsalter.

We report on a 6 months old infant with suddenly developed severe arterial hypertension caused by polycystic kidneys. Examinations of the relatives revealed similar changes of the kidneys in 4 adults and 5 children. They were all diagnosed to have autosomal dominant polycystic kidney disease. Excretory kidney function of all patients is normal; however, blood pressure was raised in the adults. We would like to stress the importance of family screening in this disease, in particular with regard to possible early diagnosis and treatment of arterial hypertension. The long-term prognosis of the early manifestation of the dominantly inherited cystic kidney disease is uncertain.