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Background. Prognosis of fetuses with renal oligohydramnios (ROH) is often still regarded as poor. Neonatal complications and the long-term follow-up of fetuses with ROH in two pediatric centres are described. Method. 23 fetuses (16 males, 7 females) were included as patients. Primary diseases included congenital anomalies of the kidney and urinary tract (n ¼ 16), autosomal recessive polycystic kidney disease (n ¼ 4) and renal tubular dysgenesis (n ¼ 3). The analysis includes retrospective chart review. Results. Seven children died (30%), the majority (n ¼ 4, 17%) within the neonatal period due to pulmonary hypoplasia and renal insufficiency. Fourteen patients (61%) required postnatal mechanical ventilation for a median of 4 (range 1–60) days; 11 infants had an associated pneumothorax. All 16 surviving children have chronic kidney disease (CKD) at a current median age of 5.7 years (range 0.5–14.5), managed conservatively in eight patients [median glomerular filtration rate 51 (range 20–78) ml/min/1.73 m 2 ]. Eight patients reached end-stage renal disease at a median age of 0.3 years (range 2 days to 8.3 years), including one patient with pre-emptive kidney transplantation. Five of the patients requiring dialysis underwent successful renal transplantation at a median age of 3.5 years (range 2.5–4). Growth was impaired in seven children requiring growth hormone treatment. Cognitive and motor development was normal in 12 (75%) of the 16 patients and showed a delay in four children, including two with associated syndromal features. Conclusion. ROH is not always associated with a poor prognosis and long-term outcome in survivors is encouraging. The high incidence of neonatal complications and long-term morbidity due to CKD requires a multidisciplinary management of these children.

Background. In patients with refractory steroid-sensitive nephrotic syndrome (SSNS), treatment with rituximab has shown encouraging results; however, long-term follow-up data are not available. Methods. We performed a retrospective analysis of 37 patients (25 boys) with steroid-dependent nephrotic syndrome who were treated with rituximab (375 mg/m 2 given weekly for one to four courses). Long-term follow-up data (>2 years, median 36, range 24–92.8 months) are available for 29 patients (12 boys). Results. Twenty-six of 37 (70.3%) patients remained in remission after 12 months. Relapses occurred in 24 (64.8%) patients after a median of 9.6 (range 5.2–64.1) months. Time to first relapse was significantly shorter in patients receiving one or two compared to three or four initial infusions. In the 29 patients with long-term follow-up for >2 years, 12 (41%) patients remained in remission after the initial rituximab course for >24 months, 7 (24.1%) patients without further maintenance immunosuppression. Nineteen children received two to four repeated courses of rituximab increasing the total number of patients with long-term remission to 20 (69%), remission including 14 (48%) patients off immunosuppression. The proportion of patients with long-term remission was not related to the number of initial rituximab applications. No serious side effects were noted. Conclusion. Rituximab is an effective treatment option in the short- and long-term control of treatment refractory SSNS. Further controlled studies are needed to address optimal patient selection, dose and safety of rituximab infusions.

BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) [MIM 263200] belongs to a group of congenital hepatorenal fibrocystic syndromes and is caused by mutations in the PKHD1 gene encoding the multidomain protein fibrocystin/polyductin (FPC). The serine-threonine kinase mammalian target of rapamycin (mTOR) is one of the most important gate-keepers integrating numerous signals related to cell proliferation and growth. Whereas the direct activation of mTOR has been shown recently in autosomal-dominant PKD, no data are available on the role of mTOR signalling in proliferation and progression of ARPKD. METHODS: Formalin-fixed and paraffin-embedded kidney specimens obtained during nephrectomy from children with ARPKD (n = 12) were used for immunohistochemical investigation of FPC expression (monoclonal antibody (mAb) 18, mAb 5a), proliferative activity (Ki-67) and activation of the mTOR pathway. Kidney specimens from children (n = 4) who died from causes not associated with kidney disease served as controls. For the detection of AKT, mTOR and S6K antibodies specifically recognizing the activated (phosphorylated) isoforms of these proteins were used. In all patients mutation analysis of the PKHD1 gene was performed. RESULTS: In 10 out of 12 patients, we could confirm the diagnosis by the identification of PKHD1 mutations. The tubular cyst epithelium of all kidney specimens stained strongly positive with the FPC-specific monoclonal antibody (mAb) 18 but only very faint signals were obtained with mAb 5a. In contrast, healthy kidneys showed rather weak signals with both FPC-specific mAbs, indicating dysregulated expression of FPC in our patients. Phosphorylated AKT as well as activated mTOR and its down-stream effector S6K were strongly expressed in cystic epithelia of all kidney specimens but not in control tissues. No association between the activation of this pathway and the proliferative activity (Ki-67 expression) was observed. CONCLUSIONS: Our results point to a central role of AKT/mTOR signalling in ARPKD and justify further investigations to evaluate the therapeutic potential of mTOR inhibitors in ARPKD patients.

Although clinical outcome data on fetuses with oligohydramnios of renal origin are scarce, prognosis is regarded as poor due to a high risk of renal dysfunction and pulmonary hypoplasia. This review aims to summarize the current knowledge and clinical experience with patients presenting antenatally with renal oligohydramnios. By reviewing the underlying mechanisms, complications, and outcome data, we hope to further improve antenatal counseling and postnatal care. We conclude that prognosis of ROH has changed in recent years. While early data before the introduction of sophisticated neonatal intensive care and renal replacement therapy indicated a poor prognosis, nowadays, a much more optimistic prognosis of children after renal oligohydramnios can be expected from the recent publications in the literature.

Background. In patients with steroid-dependent nephrotic syndrome (SDNS), long-term remission (LTR) can usually be achieved with cyclosporin A (CSA), after alternative treatment with cytotoxic drugs or levamisole has failed. Nevertheless, severe SDNS recurs in some patients despite CSA maintenance therapy. Few data are available on the clinical course and treatment strategies in these patients. Methods. We carried out a retrospective chart analysis of 46 patients with SDNS treated with CSA, after failure of cyctotoxic treatment with cyclophosphamide (CPO). Median age at primary manifestation was 3.0 years (range 0.8–6.9) and median current age is 20.4 years (range 8.6–29.1). Patients were recruited from three centres caring for a total of 186 patients with steroid-sensitive nephrotic syndrome. Results. In 14 of the 46 patients (30%; 10 male), severe SDNS recurred again despite CSA maintenance therapy. Seven patients relapsed beyond the age of 18 years. Nine of 14 patients received a further course of cytotoxic treatment as first intervention: six were treated with chlorambucil (CLA) and three with CPO. Four of the CLA-treated patients remained in LTR in contrast to none after CPO. Five patients received levamisole after CSA: only one went into LTR, while in one other CSA could be discontinued although further relapses occurred. One further patient was switched to CLA after levamisole, finally inducing LTR. Overall, six patients required two or more drugs, and in four of these CSA maintenance ultimately had to be restarted. Conclusion. We conclude that SDNS can recur in patients despite CSA maintenance therapy. Treatment strategies for this subgroup of patients are complex and should be standardized to optimize long-term outcome. A subgroup of patients with childhood SDNS continues to relapse into adulthood.

Thrombotic thrombocytopenic purpura (TTP) is caused by the persistence of the highly reactive high-molecular-weight multimers of von Willebrand factor (VWF) due to deficiency of the specific VWF-cleaving protease (VWF-CP) ADAMTS13, resulting in microangiopathic disease. The acquired form is caused by autoantibodies against VWF-CP, whereas homozygous or compound heterozygous mutations of ADAMTS13 are responsible for recessively inherited TTP. We investigated 83 children with hemolytic or thrombocytopenic episodes with or without additional neurologic symptoms or renal failure. The presumed diagnosis was chronic idiopathic thrombocytopenic purpura (ITP; n = 50), TTP (n = 8), hemolytic uremic syndrome (HUS; n = 24), and Evans syndrome (n = 1). A severe deficiency of VWF-CP (≤ 5%) was found in all investigated patients with TTP and in none of those with HUS. Additionally, 2 of 50 patients with a prior diagnosis of ITP were deficient for VWF-CP. Antibodies against VWF-CP were found in 4 children. Mutation analysis of the ADAMTS13 gene in the patients deficient in VWF-CP by direct sequencing of all 29 exons identified 8 different mutations, suggesting the hereditary form of TTP in 1 patient with ITP, in the patient with Evans syndrome, and in 5 of the 8 patients with TTP. The phenotype of TTP in childhood can be rather variable. Besides the classical clinical picture, oligosymptomatic forms may occur that can delay the identification of patients at risk.