IntroductionDysfunctional voiding is a frequent condition in children associated with symptoms of incontinence. The aim of this study was to present the efficacy of biofeedback treatment on the resolution of clinical symptoms in a large cohort of children with urodynamically confirmed dysfunctional voiding.Material and methods81 children (75 girls and 6 boys) aged 6-18 years (mean: 10.32 ±3.17 yrs.) with a dysfunctional voiding pattern are presented. 74/81 (92.6%) of children were unresponsive to standard urotherapy and prior pharmacotherapy. Symptoms of bladder dysfunction were evaluated by questionnaire, bladder diary and an urodynamic study according to definitions and standards set by ICCS. The biofeedback training was planned for 2 months. Each session consisted of about 30 repeats of 5 s contraction and 30 s relaxation of pelvic floor muscles and external urethral sphincter. Biofeedback was performed together with standard urotherapy.Results67 (82.72%) of the 81 children declared wetting during the day and 41 (50, 62%) – wetting during the night. 32/81 (39.5%) children had increased voiding frequency and 43 (53.08%) had decreased bladder capacity. Following 2 months of biofeedback therapy daytime incontinence resolved in 34/67 (50.7%) children and nighttime incontinence in 22/41 (53.65%). A further 40,3% declared partial improvement in daytime and 26.7% in nighttime wetting.ConclusionsBiofeedback treatment is an effective therapeutic option for children with dysfunctional voiding. Pelvic floor therapy with biofeedback should be offered to children with dysfunctional voiding resistant to standard urotherapy.

The aim of the study was a multicenter analysis of the efficacy and safety of a nonstandard immunosuppressive therapy with rituximab (Rtx) in children with steroidresistant nephrotic syndrome (SRNS) with particular emphasis on the possibility of permanent discontinuation or dose reduction of other immunosuppressive drugs such as glucocorticoids and cyclosporine A after 6 months of observation. The study group consisted of 30 children with idiopathic nephrotic syndrome, who were unresponsive to standard immunosuppressive treatment, and hospitalized in the years 2010-2017 in eight paediatric nephrology centres in Poland. The children were administered a single initial infusion of rituximab at the dose of 375 mg/m 2 of the body surface area. Proteinuria, the daily supply of glucocorticoids, and cyclosporine were assessed at the moment of the start of the treatment and after 6 months since its commencement. Before Rtx therapy, complete remission was found in 13 patients (43%) and partial remission was found in 8 patients (26%). These numbers increased to 16 (53%) and 12 (40%), respectively. At the start of the treatment 23 patients (76.6%) were treated with cyclosporine A. After 6 months, this number decreased to 15 patients (35%). At the start of the treatment, 18 patients (60%) were treated with prednisone. After 6 months, this number decreased to 8 patients (44%). Children with SRNS may potentially benefit from Rtx treatment despite relative risk of side effects. The benefits may include reduction of proteinuria or reduction of other immunosuppressants. K E Y W O R D Scyclosporine A, glomerulonephritis, glucocorticoids, nephrology, paediatrics

The aim of the study was to evaluate the influence of the intensity of mesangial C3 deposits in kidney biopsy and the serum C3 level on the clinical course and outcomes of IgAN in children. The study included 148 children from the Polish Pediatric IgAN Registry, diagnosed based on kidney biopsy. Proteinuria, creatinine, IgA, C3 were evaluated twice in the study group, at baseline and the end of follow-up. Kidney biopsy was categorized using the Oxford classification, with a calculation of the MEST-C score. The intensity of IgA and C3 deposits were rated from 0 to +4 in immunofluorescence microscopy. The intensity of mesangial C3 > +1 deposits in kidney biopsy has an effect on renal survival with normal GFR in children with IgAN. A reduced serum C3 level has not been a prognostic factor in children but perhaps this finding should be confirmed in a larger group of children.

Background There is paucity of information on rituximab-associated hypogammaglobulinemia (HGG) and its potential infectious consequences in children treated for idiopathic nephrotic syndrome (INS). Methods A survey was distributed by the European Society Pediatric Nephrology to its members. It addressed the screening and management practices of pediatric nephrology units for recognizing and treating RTX-associated HGG and its morbidity and mortality. Eighty-four centers which had treated an overall 1328 INS children with RTX responded. Results The majority of centers administered several courses of RTX and continued concomitant immunosuppressive therapy. Sixty-five percent of centers routinely screened children for HGG prior to RTX infusion, 59% during, and 52% following RTX treatment. Forty-seven percent had observed HGG prior to RTX administration, 61% during and 47% >9 months following treatment in 121, 210, and 128 subjects respectively. Thirty-three severe infections were reported among the cohort of 1328 RTX-treated subjects, of whom 3 children died. HGG had been recognized in 30/33 (80%) of them. Conclusions HGG in steroid-dependent/frequently relapsing nephrotic syndrome (SDNS/FRNS) children is probably multifactorial and can be observed prior to RTX administration in children with SDNS/FRNS. Persistent HGG lasting >9 months from RTX infusion is not uncommon and may increase the risk of severe infections in this cohort. We advocate for the obligatory screening for HGG in children with SDNS/FRNS prior to, during, and following RTX treatment. Further research is necessary to identify risk factors for developing both HGG and severe infections before recommendations are made for its optimal management. Graphical abstract

Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional signals. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. We conducted a multi-population GWAS meta-analysis in 38,463 participants (2,440 cases) and population specific GWAS, discovering twelve significant associations (eight novel). Fine-mapping implicated specific amino acid haplotypes in HLA-DQA1 and HLA-DQB1 driving the HLA Class II risk signal. Non-HLA loci colocalized with eQTLs of monocytes and numerous T-cell subsets in independent datasets. Colocalization with kidney eQTLs was lacking, but overlap with kidney cell open chromatin suggests an uncharacterized disease mechanism in kidney cells. A polygenic risk score (PRS) associated with earlier disease onset in two independent cohorts. Altogether, these discoveries expand our knowledge of pSSNS genetic architecture across populations and provide cell-specific insights into its molecular drivers.