The choice of dialysis solutions in pediatric chronic peritoneal dialysis : guidelines by an AD HOC European committee

Objective: To provide guidelines on choosing dialysis solutions for children on chronic peritoneal dialysis (PD). Setting: European Paediatric Peritoneal Dialysis Working Group. Data Source: Literature on the application of PD solutions in children (Evidence), and discussions within the group (Opinion). Conclusions: Glucose is the standard osmotic agent for PD in children (Evidence). The lowest glucose concentration needed should be used (Opinion). Low calcium solution (1.25 mmol/L) should be applied, wherever possible, with careful monitoring of parathyroid hormone levels (Opinion). The use of amino acid-containing dialysis fluids can be considered in malnourished children, although aggressive enteral nutrition is preferred (Opinion). There is insufficient evidence documenting the efficacy of intraperitoneally administered amino acids (Evidence). When ultrafiltration and/or solute removal are insufficient, poly-glucose solutions are a welcome addition to the treatment of children on nocturnal intermittent PD (Evidence). However, in the absence of any reported long-term experience with children, their use must be closely monitored (Opinion). Bicarbonate would appear to be the preferred buffer for PD in children, but more in vivo studies are required before it replaces the present lactate-containing solutions (Evidence/Opinion)

Indications, technique, and outcome of therapeutic apheresis in European pediatric nephrology units

Few observations on apheresis in pediatric nephrology units have been published. This retrospective study involved children a parts per thousand currency sign18 years undergoing plasma exchange (PE), immunoadsorption (IA), or double filtration plasmapheresis (DFPP) in 12 European pediatric nephrology units during 2012. Sixty-seven children underwent PE, ten IA, and three DFPP, for a total of 738 PE and 349 IA/DFPP sessions; 67.2 % of PE and 69.2 % of IA/DFPP patients were treated for renal diseases, in particular focal segmental glomerulosclerosis (FSGS), hemolytic-uremic syndrome (HUS), and human leukocyte antigen (HLA) desensitization prior to renal transplantation; 20.9 % of PE and 23.1 % of IA/DFPP patients had neurological diseases. Membrane filtration was the most common technique, albumin the most frequently used substitution fluid, and heparin the preferred anticoagulant. PE achieved full disease remission in 25 patients (37.3 %), partial remission in 22 (32.8 %), and had no effect in 20 (29.9 %). The response to IA/DFPP was complete in seven patients (53.8 %), partial in five (38.5 %), and absent in one (7.7 %). Minor adverse events occurred during 6.9 % of PE and 9.7 % of IA/DFPP sessions. PE, IA, and DFPP are safe apheresis methods in children. Efficacy is high in pediatric patients with recurrent focal segmental glomerulosclerosis (FSGS), atypical hemolytic uremic syndrome (HUS), human leukocyte antigen (HLA) sensitization, and neurological autoimmune diseases

Long-Term Outcome of Steroid-Resistant Nephrotic Syndrome in Children

We investigated the value of genetic, histopathologic, and early treatment response information in prognosing long-term renal outcome in children with primary steroid-resistant nephrotic syndrome. From the PodoNet Registry, we obtained longitudinal clinical information for 1354 patients (disease onset at >3 months and <20 years of age): 612 had documented responsiveness to intensified immunosuppression (IIS), 1155 had kidney biopsy results, and 212 had an established genetic diagnosis. We assessed risk factors for ESRD using multivariate Cox regression models. Complete and partial remission of proteinuria within 12 months of disease onset occurred in 24.5% and 16.5% of children, respectively, with the highest remission rates achieved with calcineurin inhibitor based protocols. Ten-year ESRD-free survival rates were 43%, 94%, and 72% in children with IIS resistance, complete remission, and partial remission, respectively; 27% in children with a genetic diagnosis; and 79% and 52% in children with histopathologic findings of minimal change glomerulopathy and FSGS, respectively. Five-year ESRD-free survival rate was 21% for diffuse mesangial sclerosis. IIS responsiveness, presence of a genetic diagnosis, and FSGS or diffuse mesangial sclerosis on initial biopsy as well as age, serum albumin concentration, and CKD stage at onset affected ESRD risk. Our findings suggest that responsiveness to initial IIS and detection of a hereditary podocytopathy are prognostic indicators of favorable and poor long-term outcome, respectively, in children with steroid-resistant nephrotic syndrome. Children with multidrug-resistant sporadic disease show better renal survival than those with genetic disease. Furthermore, histopathologic findings may retain prognostic relevance when a genetic diagnosis is established

IPNA clinical practice recommendations for the diagnosis and management of children with steroid-sensitive nephrotic syndrome

Idiopathic nephrotic syndrome is the most frequent pediatric glomerular disease, affecting from 1.15 to 16.9 per 100,000 children per year globally. It is characterized by massive proteinuria, hypoalbuminemia, and/or concomitant edema. Approximately 85–90% of patients attain complete remission of proteinuria within 4–6 weeks of treatment with glucocorticoids, and therefore, have steroid-sensitive nephrotic syndrome (SSNS). Among those patients who are steroid sensitive, 70–80% will have at least one relapse during follow-up, and up to 50% of these patients will experience frequent relapses or become dependent on glucocorticoids to maintain remission. The dose and duration of steroid treatment to prolong time between relapses remains a subject of much debate, and patients continue to experience a high prevalence of steroid-related morbidity. Various steroid-sparing immunosuppressive drugs have been used in clinical practice; however, there is marked practice variation in the selection of these drugs and timing of their introduction during the course of the disease. Therefore, international evidence-based clinical practice recommendations (CPRs) are needed to guide clinical practice and reduce practice variation. The International Pediatric Nephrology Association (IPNA) convened a team of experts including pediatric nephrologists, an adult nephrologist, and a patient representative to develop comprehensive CPRs on the diagnosis and management of SSNS in children. After performing a systematic literature review on 12 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, recommendations were formulated and formally graded at several virtual consensus meetings. New definitions for treatment outcomes to help guide change of therapy and recommendations for important research questions are given

Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome

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 independent risk loci. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. Here, we conduct a multi-population GWAS meta-analysis in 38,463 participants (2440 cases). We then conduct conditional analyses and population specific GWAS. We discover twelve significant associations—eight from the multi-population meta-analysis (four novel), two from the multi-population conditional analysis (one novel), and two additional novel loci from the European meta-analysis. Fine-mapping implicates specific amino acid haplotypes in HLA-DQA1 and HLA-DQB1 driving the HLA Class II risk locus. Non-HLA loci colocalize with eQTLs of monocytes and numerous T-cell subsets in independent datasets. Colocalization with kidney eQTLs is lacking but overlap with kidney cell open chromatin suggests an uncharacterized disease mechanism in kidney cells. A polygenic risk score (PRS) associates with earlier disease onset. Altogether, these discoveries expand our knowledge of pSSNS genetic architecture across populations and provide cell-specific insights into its molecular drivers. Evaluating these associations in additional cohorts will refine our understanding of population specificity, heterogeneity, and clinical and molecular associations