Sonographic long-term study: paediatric growth charts for single kidneys.

AIMS: To explore the clinical course of children with "single kidney" (defined as either a solitary or single functioning kidney) with reference to renal function (glomerular filtration rate (GFR) and proteinuria), body height and particularly sonomorphological features. PATIENTS AND METHODS: This retrospective monocentric study evaluated 119 children with a solitary or single functioning kidney (>90% unilateral function on isotope scan) between 1997 and 2007. Patients were followed for 6.3 years (median, range 1-17) and had at least three renal ultrasound examinations (median 8). During recruitment six children were identified with chronic kidney disease (CKD) stage III or worse. These patients were analysed separately. RESULTS: The aetiology of "single kidney" was attributed to contralateral multicystic dysplastic kidney (26%), tumournephrectomy (24%), renal agenesis (18%), hypo/dysplasia (11%) and obstructive or refluxive uropathy (18%). Irrespective of aetiology, the sonographic dimensions of "single kidneys" were in the upper range of normal paired kidneys and showed adequate growth. Compensatory renal hypertrophy (defined as >95% CI on two or more recent measurements) occurred in a third of patients. All six patients with CKD and GFR less than 60 ml/minute per 1.73 m(2) had pathological sonomorphology of their "single kidney" with inadequate renal growth (6/6), abnormal echogenicity (5/6), hypo/dysplasia (5/6). In addition, proteinuria (5/6) and short stature (3/6) were found. CONCLUSIONS: New reference centiles were generated to assess renal size of "single kidneys" in paediatric patients. These charts will facilitate counselling of patients and parents. Further evidence for a benign clinical course of children with "single kidney" and absent additional pathology of the remnant kidney is presented.

[Successful continuous renal replacement therapy in a neonate with early-onset group B streptococcal sepsis and multi-organ dysfunction syndrome]. / Multiorganversagen bei Early-onset-B-Streptokokkensepsis: Erfolgreicher Einsatz einer kontinuierlichen venovenösen Hämofiltration (CVVH) beim Neugeborenen.

BACKGROUND: Group B streptococcal early-onset sepsis (GBS EOS) in neonates has a mortality rate of approximately 5%, particularly in the presence of multi-organ dysfunction. Fluid management is crucial in these patients, and continuous venovenous haemofiltration (CVVH) should be considered a therapeutic option even in newborn babies. CASE REPORT: After an uneventful pregnancy within hours after birth, a female term infant presented with dyspnoea, irritability and cyanosis. The systemic inflammatory response syndrome (SIRS) progressed to multi-organ dysfunction with acute respiratory distress syndrome (ARDS), impaired myocardial contractility, pulmonary hypertension and fluid overload. The maximum PRISM score was 51. The child required maximal respiratory and inotropic support with high volume intravenous fluid administration. However, only by using of CVVH from day 5 to 14, we successfully resolved progressive pulmonary and cardiovascular dysfunction. The child improved directly after initiation of fluid removal, was extubated on day 17 and discharged without obvious sequelae on day 57. All microbiology studies revealed GBS. CONCLUSION: Perinatal GBS-infections remain a major life-threatening event for newborn babies. CVVH should be considered an option for reversing fluid overload even in neonates with overwhelming SIRS. Alternatively, extracorporeal membrane oxygenation (ECMO) is discussed.

[Left flank tumor of fluctuating size in a 5-week-old boy: perirenal urinoma caused by urethral valves]. / Perirenales Urinom durch Urethralklappen bei einem Säugling mit fluktuierender Flankenschwellung.

BACKGROUND: Flank swelling and pseudotumors of the kidney are unusual manifestations of obstructive uropathies in small children. Our case illustrates typical problems and briefly reviews management options. CASE REPORT: A 5-week-old boy presented with a large, palpable urinoma due to posterior urethral valves. Sonography and voiding cystourethrogram led to the diagnosis and immediate suprapubic transcutaneous urinary diversion was performed. However, the urinoma did not resolve. Thus, in addition to suprapubic urinary diversion, indirect drainage - instead of percutaneous puncture - was performed by retrograde insertion of a double-J catheter. Urethral valves were resected 4 weeks later and follow-up demonstrated an uneventful further development with normal renal function as assessed by regular ultrasound studies, a repeat cystourethrogram and a renal scan. CONCLUSION: Perirenal urinomas may be the first symptom in patients with posterior urethral valves. Drainage via double-J stenting offers a promising alternative to percutaneous puncture. A renoprotective "pop-off" mechanism by which intrarenal pressure may be relieved is discussed.

[Sclerosing peritonitis without reduced ultrafiltration as complication of peritoneal dialysis]. / Sklerosierende Peritonitis als Komplikation bei Peritonealdialyse.

UNLABELLED: Peritoneal dialysis (PD) is the preferred method of renal replacement therapy in childhood and adolescence while waiting for a kidney transplant. As major complication, encapsulating peritoneal sclerosis (EPS), sometimes also referred to as "sclerosing peritonitis", may develop after prolonged periods of PD and lead to severe therapeutical problems. CASE REPORT: A 20-year-old patient with a history of three unsuccessful kidney transplants due to recurrence of his focal segmental glomerulosclerosis presented after 9 years of PD with acute abdominal pain and reduced bowel movements. Infectious peritonitis was excluded, ultrafiltration with 800-1 000 ml per day with low (1,36 %) glucose dialysate was not impaired. Plain abdominal X-ray, ultrasound and CT-scan illustrated characteristic peritoneal calcifications. Diagnosis of EPS was confirmed by peritoneal biopsy. The patients was switched to hemodialysis, enteral nutrition was continued, and the follow-up (now 16 months) was uncomplicated with the exception of a sterile ascites, which was twice relieved. Diagnostic and therapeutic options are discussed. CONCLUSION: In contrast to most reports, EPS may develop with unchanged ultrafiltration after prolonged periods of PD. We recommend regular functional and imaging studies in patients at risk.

Permanent pacemaker implantation in a 1,445 g preterm neonate on the first day of life.

Here, we present a case involving a very low-birthweight baby (1445 g) born prematurely after 30 weeks of gestation with congenital complete heart block and low-output failure. The newborn was successfully treated by implantation of an epimyocardial pacemaker on her first day of life.

[Case report: neonatal hypertension]. / Kasuistik: neonatale arterielle Hypertonie.

BACKGROUND: Neonatal arterial hypertension is rare with an incidence between 0.2 - 3 %. Clinical presentation varies widely and is in some cases dramatic. PATIENT: A 4-day old full-term neonate was admitted to the intensive care unit with severe congestive heart failure and metabolic acidosis. Mechanical ventilation was initiated and dobutamine administered because of poor systolic function. Continuous monitoring of blood pressure revealed severe arterial hypertension (30 to 40 mm Hg above the 95th percentile). Ultrasonography showed an echogenic left kidney with normal perfusion. Laboratory examinations revealed a raised peripheral renin activity, thrombocytopenia, slightly raised d-dimers, a microhematuria and mild proteinuria. After resolution of hypertension under therapy with an ACE-inhibitor, a MAG3 renal scan showed complete absence of renal function on the left side. Renal artery stenosis was excluded by venous transcardial angiography. Under therapy with Captopril, the patient was discharged and followed up for 8 months. He is developing normally with normal serum creatinine (0.4 mg/dl), but low renal function (17 %) of the left side as assessed by DMSA-scan and compensatory right kidney hypertrophy are observed. DISCUSSION: Diagnosis and treatment of neonatal hypertension are discussed with respect to the proposed case. After exclusion of other causes we conclude that a perinatal microangiopathic event may have lead to the renal lesions with malignant renovascular hypertension.

[Pseudo-Acanthosis nigricans in a 12 year old boy after kidney transplantation]. / Pseudo-Acanthosis nigricans bei einem 12 Jahre alten Jungen nach Nierentransplantation.

Cutaneous lesions under immunosuppressive therapy require a specific diagnostic approach. We present the case of a 12 year old boy who developed pseudo-acanthosis nigricans 3 months after renal transplantation.

A meta-analysis of cytotoxic treatment for frequently relapsing nephrotic syndrome in children.

For over 30 years cyclophosphamide (CYC) and chlorambucil (CHL) have been used to treat children with relapsing steroid-sensitive nephrotic syndrome (SSNS). A meta-analysis on treatment protocols, efficacy, and side effects of CYC and CHL was performed from the literature. Thirty-eight studies comprising 1,504 children and 1,573 courses of cytotoxic drug therapy were systematically evaluated. Relapse-free survival rates increased with the cumulative dosage of CHL and CYC and were higher in children with frequently relapsing than steroid-dependent NS. The fatality rate of the treatment was approximately 1%. Leukopenia occurred in one-third of patients treated with either drug. Severe bacterial infections developed in 1.5% of the patients under CYC and in 6.8% under CHL. Seizures were observed in 3.6% of children treated with CHL. Malignancies were observed in 14 children after high doses of either drug. Females rarely developed permanent gonadal damage. However, no safe threshold for a cumulative amount of CYC was found in males, but there was a marked increase in the risk of oligo- or azoospermia with higher cumulative doses. From this meta-analysis we recommend CYC 2-3 mg/kg body weight for 8-12 weeks as the standard scheme. CHL has higher rates of severe side effects and should be considered a second-line drug.

Post-transplant epididymitis and orchitis following Listeria monocytogenes septicaemia.

We report the occurrence of epididymitis and orchitis 1 week after the onset of Listeriosis in an 11-month-old boy receiving an orthotopic liver transplantation for biliary atresia. Immunologic implications of Listeria monocytogenes-induced testicular inflammation are discussed, and the potential role of immunosuppression with tacrolimus is also discussed.

Variable presentation of primary hyperoxaluria type 1 in 2 patients homozygous for a novel combined deletion and insertion mutation in exon 8 of the AGXT gene.

Two unrelated patients of Pakistani origin presented with primary hyperoxaluria type 1 (PH1) at 4 months and 3 years of age, respectively. While the younger patient failed to thrive and suffered from early renal failure, the older one showed a relatively benign history with urolithiasis as the main feature of the disease. In both patients the diagnosis was confirmed by assessment of alanine:glyoxylate aminotransferase catalytic and immunoreactivity in liver biopsy specimens. The underlying genetic defect was found to be a combined deletion and insertion in exon 8 which alters the reading frame of the protein. The nucleotide change introduces a Stu1 restriction site which facilitated typing of additional family members. Both patients and a further affected brother were homozygous for this mutation, while their parents were heterozygous for it. This mutation is the first deletion/insertion identified in PH1. Although rare in our PH1 patient cohort (2.5% of alleles), the finding of 2 homozygous apparently unrelated individuals of the same ethnic origin suggests that it may prove worthwhile to screen other Asian patients for this mutation. These PH1 cases present further evidence that factors other than genotype contribute significantly to the clinical presentation and severity of PH1.

Identification of new mutations in primary hyperoxaluria type 1 (PH1).

Primary hyperoxaluria type 1 (PH1) is caused by deficiency of the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). The AGXT gene, which codes for the 392 amino acid protein, has been mapped to chromosome 2q37.3. In order to identify new mutations in the AGXT gene we studied 79 PH1 patients using single strand conformation polymorphism analysis. In addition to a cluster of new mutations in exon 7 we report five novel mutations in exons 2, 4, 5, 9 and 10. These are T444C, G640A, G690A, 1008-1010delGCG and G1171A. These five new mutations contribute to our knowledge of the AGXT gene. Their possible consequences for PH1 phenotype and enzyme activity are discussed.

Primary hyperoxaluria type 1: diagnostic relevance of mutations and polymorphisms in the alanine:glyoxylate aminotransferase gene (AGXT).

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder of glyoxylate metabolism caused by deficiency of the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). The disease shows considerable phenotypic, enzymatic and genetic heterogeneity. To date, 7 polymorphisms and 11 point mutations have been described in the gene encoding AGT. We report on the prevalence of these polymorphisms and mutations in 79 patients with PH1 with the aim of assessing their diagnostic relevance. A strong association of the C154T, intron 1 insertion and C386T polymorphisms is confirmed and this linkage extends to include the type 1 variant of a polymorphic tandem repeat in intron 4. Only 64 of 158 (40%) PH1 alleles have one of the defined mutations, with the G630A mutation accounting for 39 of these and T853C for 14. Overall only 20 (25%) of the patients studied had the genetic basis of their disease fully explained: 7 were homozygous for the G630A mutation, 5 were homozygous for the T853C mutation, 1 was homozygous for the C819T mutation, and 7 had two different mutations identified and were presumed to be compound heterozygotes. Only the two more frequent G630A and T853C mutations are of general diagnostic relevance for mutation screening. It seems likely that there are a significant number of other mutations, perhaps family-specific, still to be described. There was no apparent difference in the types of mutations in patients presenting in the first year of life (36%), suggesting that other factors, such as periods of dehydration or urinary tract infections, might contribute more to the clinical manifestation than genotype.

Linkage of microsatellites to the AGXT gene on chromosome 2q37.3 and their role in prenatal diagnosis of primary hyperoxaluria type 1.

Defects in the AGXT gene mapped to chromosome 2q37.3 cause primary hyperoxaluria type 1 (PH1), one of the inherited disorders of endogenous oxalate overproduction. In order to identify diagnostically useful linkage markers in this region of chromosome 2 we have typed three microsatellite loci mapping to the q37 region of chromosome 2 in 192 individuals from 30 families. They were additionally studied for mutations and polymorphisms in the AGXT gene. Maximum lod scores of 29.1, 22.8 and 15.8 were obtained for D2S140, D2S125 and D2S395 respectively at recombination fractions (theta) of 0.001, 0.015 and 0.02. Confidence intervals for recombination as determined by the 'lod-1 rule' were 0.015, 0.05 and 0.06. Three recombinants were identified between AGXT and D2S125/D2S395, whereas no recombination between AGXT and D2S140 was observed. These data allow the calculation of the risk of incorrect prenatal diagnosis of PH1 based solely on linkage analysis with these extragenic markers.

Primary hyperoxaluria type 1: a cluster of new mutations in exon 7 of the AGXT gene.

Primary hyperoxaluria type 1 (PH1) is a severe autosomal recessive inborn error of glyoxylate metabolism caused by deficiency of the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase. This enzyme is encoded by the AGXT gene on chromosome 2q37.3. DNA samples from 79 PH1 patients were studied using single strand conformation polymorphism analysis to detect sequence variants, which were then characterised by direct sequencing and confirmed by restriction enzyme digestion. Four novel mutations were identified in exon 7 of AGXT: a point mutation T853C, which leads to a predicted Ile244Thr amino acid substitution, occurred in nine patients. Two other mutations in adjacent nucleotides, C819T and G820A, mutated the same codon at residue 233 from arginine to cysteine and histidine, respectively. The fourth mutation, G860A, introduced a stop codon at amino acid residue 246. Enzyme studies in these patients showed that AGT catalytic activity was either very low or absent and that little or no immunoreactive protein was present. Together with a new polymorphism in exon 11 (C1342A) these findings underline the genetic heterogeneity of the AGXT gene. The novel mutation T853C is the second most common mutation found to date with an allelic frequency of 9% and will therefore be of clinical importance for the diagnosis of PH1.

Determination of oxalate excretion in spot urines of healthy children by ion chromatography.

Evidence for the suitability of spot urines for selective screening in children was obtained by comparing the 24-hour urinary oxalate excretion with the ratio of urinary oxalate to creatinine [mmol/mol] in spontaneously voided urine samples. Spot urines of 169 healthy children aged 1 day to 13 years were analysed in order to establish reference values for the urinary oxalate/creatinine ratio in relation to age and body surface area. Oxalate was measured by automated ion chromatography. Results showed an inverse relationship between the oxalate/creatinine ratio and age. The highest ratios, 131 +/- 57 mmol/mol (mean +/- 2 SD), were found in infants. At age two years, the ratio was 84 +/- 55, at age five years 56 +/- 35, and for children older than ten years 42 +/- 31. This finding can be explained by the gain of muscle mass and hence increased creatinine production with increasing age. Data for the urinary oxalate/creatinine ratio are presented according to body surface area for the assessment of children with abnormal growth. In 19 urine samples from nine patients with primary hyperoxaluria, the oxalate/creatinine ratio greatly exceeded (286-2022 mmol/mol) the above reference ranges. We therefore propose the determination of the oxalate/creatinine ratio in spot urines for the selective screening for hyperoxaluria in children with nephrocalcinosis or urolithiasis.