The aim of this study was to establish the efficacy and safety of rituximab in refractory nephrotic syndrome (NS). Members of the International Paediatric Nephrology Association were asked to retrospectively fill in a questionnaire with details on the use of rituximab in their centres. We divided the data into three groups: group 1, patients with steroid-dependent and frequently relapsing NS; group 2, with steroid-resistant NS; group 3, with post-transplant recurrence of NS. Seventy questionnaires from 25 centres described the outcome of 28, 27 and 15 patients in groups 1, 2 and 3, respectively. Of these, 82% of patients in group 1, 44% of patients in group 2 and 60% of patients in group 3 had a good initial response. Side effects were observed in 27% of the patients, and these were mostly acute reactions. We present a large multicentre series of children with refractory NS. Children in group 1 showed the best response. The good initial response in group 3 can be biased by the accompanying treatments that were administered at the same time as rituximab. Controlled prospective trials are required to establish the value of rituximab in idiopathic NS.

In patients beyond the first year after transplantation, there is a cumulative effect of CYP3A5*1 polymorphism and weight on the tacrolimus C 0. Children with lower weight and carriers of the CYP3A5*1 allele have higher weight-normalised tacrolimus dose requirements.

The calcineurin inhibitor tacrolimus, cornerstone of most immunosuppressive regimens, is a drug with a narrow therapeutic window: underexposure can lead to allograft rejection and overexposure can result in an increased incidence of infections, toxicity and malignancies. Tacrolimus is metabolised in the liver and intestine by the cytochrome P450 3A (CYP3A) isoforms CYP3A4 and CYP3A5. This review focusses on the clinical aspects of tacrolimus pharmacodynamics, such as efficacy and toxicity. Factors affecting tacrolimus pharmacokinetics, including pharmacogenetics and the rationale for routine CYP3A5*1/*3 genotyping in prospective paediatric renal transplant recipients, are also reviewed. Therapeutic drug monitoring, including pre-dose concentrations and pharmacokinetic profiles with the available "reference values", are discussed. Factors contributing to high intra-patient variability in tacrolimus exposure and its impact on clinical outcome are also reviewed. Lastly, suggestions for future research and clinical perspectives are discussed.

Primary hyperoxaluria (PH) is an inherited disorder that results from the overproduction of endogenous oxalate, leading to recurrent kidney stones, nephrocalcinosis and eventually kidney failure; the subsequent storage of oxalate can cause life-threatening systemic disease. Diagnosis of PH is often delayed or missed owing to its rarity, variable clinical expression and other diagnostic challenges. Management of patients with PH and kidney failure is also extremely challenging. However, in the past few years, several new developments, including new outcome data from patients with infantile oxalosis, from transplanted patients with type 1 PH (PH1) and from patients with the rarer PH types 2 and 3, have emerged. In addition, two promising therapies based on RNA interference have been introduced. These developments warrant an update of existing guidelines on PH, based on new evidence and on a broad consensus. In response to this need, a consensus development core group, comprising (paediatric) nephrologists, (paediatric) urologists, biochemists and geneticists from OxalEurope and the European Rare Kidney Disease Reference Network (ERKNet), formulated and graded statements relating to the management of PH on the basis of existing evidence. Consensus was reached following review of the recommendations by representatives of OxalEurope, ESPN, ERKNet and ERA, resulting in 48 practical statements relating to the diagnosis and management of PH, including consideration of conventional therapy (conservative therapy, dialysis and transplantation), new therapies and recommendations for patient follow-up. SectionsUnanswered questions and research agenda Conclusions