Vaccination Practices in Pediatric Dialysis Patients Across Europe. A European Pediatric Dialysis Working Group and European Society for Pediatric Nephrology Dialysis Working Group Study

Background: Data on the immunization practices in pediatric chronic kidney disease (CKD) patients are scarce. The purpose of this study was to evaluate current vaccination practices for children on dialysis across European pediatric nephrology centers. Methods: A total of 18 tertiary pediatric nephrology centers from 12 European countries were included in the study. The data on universal national immunization programs and immunization practices for children with chronic disease or risk were recorded from European Center for Disease Prevention and Control and the World Health Organization. The immunization practices and center protocols for monitoring antibody titers after vaccination in dialysis patients were obtained through a questionnaire. Results: All centers included in the study recommended immunization against hepatitis B virus (HBV), diphtheria, tetanus, pertussis, Hemophilus influenzae type b (Hib), poliomyelitis, measles, mumps, rubella (MMR), and streptococcus pneumonia in dialysis patients. In 16 centers, dialysis patients were vaccinated against influenza virus annually. HBV protective antibody titers were measured in 17 centers (during dialysis period in 14 centers, during pre-renal transplantation preparations in 14 centers or in both times in 11 centers). Hepatitis A virus (HAV) was reported to be followed in 13 centers, in 8 centers during dialysis period, and in 11 centers during pre-RTx preparations. MMR and varicella-zoster virus (VZV) protective antibody titers were measured during the dialysis period or before renal transplantation (RTx) in 12 and 15 centers, respectively, and in 6 centers both titers were checked both times. Conclusion: There are variations in vaccination practice across Europe. Children with CKD, those undergoing dialysis, and transplant candidates should receive age-appropriate vaccinations before RTx as well as before the transition to adult nephrology clinics and antibody levels should be monitored to evaluate the immunization status before and after RTx. (C) 2017 S. Karger AG, Basel.Peer reviewe

Management of children with congenital nephrotic syndrome: challenging treatment paradigms

Background: Management of children with congenital nephrotic syndrome (CNS) is challenging. Bilateral nephrectomies followed by dialysis and transplantation are practiced in most centres, but conservative treatment may also be effective. / Methods: We conducted a 6-year review across members of the European Society for Paediatric Nephrology Dialysis Working Group to compare management strategies and their outcomes in children with CNS. / Results: Eighty children (50% male) across 17 tertiary nephrology units in Europe were included (mutations in NPHS1, n = 55; NPHS2, n = 1; WT1, n = 9; others, n = 15). Excluding patients with mutations in WT1, antiproteinuric treatment was given in 42 (59%) with an increase in S-albumin in 70% by median 6 (interquartile range: 3–8) g/L (P < 0.001). Following unilateral nephrectomy, S-albumin increased by 4 (1–8) g/L (P = 0.03) with a reduction in albumin infusion dose by 5 (2–9) g/kg/week (P = 0.02). Median age at bilateral nephrectomies (n = 29) was 9 (7–16) months. Outcomes were compared between two groups of NPHS1 patients: those who underwent bilateral nephrectomies (n = 25) versus those on conservative management (n = 17). The number of septic or thrombotic episodes and growth were comparable between the groups. The response to antiproteinuric treatment, as well as renal and patient survival, was independent of NPHS1 mutation type. At final follow-up (median age 34 months) 20 (80%) children in the nephrectomy group were transplanted and 1 died. In the conservative group, 9 (53%) remained without dialysis, 4 (24%; P < 0.001) were transplanted and 2 died. / Conclusion: An individualized, stepwise approach with prolonged conservative management may be a reasonable alternative to early bilateral nephrectomies and dialysis in children with CNS and NPHS1 mutations. Further prospective studies are needed to define indications for unilateral nephrectomy

The Peritoneal Surface Proteome in a Model of Chronic Peritoneal Dialysis Reveals Mechanisms of Membrane Damage and Preservation

Peritoneal dialysis (PD) fluids are cytotoxic to the peritoneum. Recent studies have shown that alanyl-glutamine (AlaGln) modulates the cellular stress response, improves mesothelial cell survival, reduces submesothelial thickening in experimental models of PD, and in clinical studies improves PD effluent cell stress and immune responses. However, the mechanisms of AlaGln-mediated membrane protection are not yet fully understood. Here, we explore those mechanisms through application of a novel proteomics approach in a clinically relevant in vivo model in rats. Experimental PD was performed for 5 weeks using conventional single-chamber bag (SCB) or neutral dual-chamber bag (DCB), PD fluid (PDF), with or without AlaGln supplementation, via a surgically implanted catheter. Rats subjected to a single dwell without catheter implantation served as controls. The peritoneal surface proteome was directly harvested by detergent extraction and subjected to proteomic analysis by two-dimensional difference gel electrophoresis (2D-DiGE) with protein identification by mass spectrometry. An integrated bioinformatic approach was applied to identify proteins significantly affected by the treatments despite biological variation and interfering high abundance proteins. From 505 of 744 common spots on 59 gels, 222 unique proteins were identified. Using UniProt database information, proteins were assigned either as high abundance plasma proteins, or as cellular proteins. Statistical analysis employed an adapted workflow from RNA-sequencing, the trimmed mean of M-values (TMM) for normalization, and a mixed model for computational identification of significantly differentially abundant proteins. The most prominently enriched pathways after 5 weeks chronic treatment with SCB or DCB, PDFs belonged to clusters reflecting tissue damage and cell differentiation by cytoskeletal reorganization, immune responses, altered metabolism, and oxidative stress and redox homeostasis. Although the AlaGln effect was not as prominent, associated enriched pathways showed mostly regression to control or patterns opposite that of the PDF effect. Our study describes the novel peritoneal surface proteome through combined proteomic and bioinformatic analyses, and assesses changes elicited by chronic experimental PD. The biological processes so identified promise to link molecular mechanisms of membrane damage and protection in the in vivo rat model to pathomechanisms and cytoprotective effects observed in vitro and in clinical PD

Oral intake of Lactobacillus pentosus strain b240 accelerates salivary immunoglobulin A secretion in the elderly: A randomized, placebo-controlled, double-blind trial

<p>Abstract</p> <p>Background</p> <p>Immunoglobulin A (IgA) secretion in saliva decreases with age and may be the cause of increased vulnerability of the elderly to respiratory infections. The effect of oral intake of lactic acid bacteria on salivary secretory IgA (SIgA) in the elderly has not been reported. The objective of this study was to demonstrate the acceleration of salivary SIgA secretion by oral intake of <it>Lactobacillus pentosus </it>strain b240 (b240) in the elderly.</p> <p>Results</p> <p>A total of 80 healthy elderly individuals were randomly allocated to either an intervention (i.e., b240) or a control (i.e., placebo) group. The elderly individuals in the b240 group were given a sterile water beverage (125 mL) containing heat-killed b240 (4 × 10⁹cells), while those in the placebo group were given only a sterile water beverage (125 mL); both groups received their respective beverages once daily for 12 weeks. Saliva was collected before initiation of the study and every 2 weeks thereafter. Saliva flow rate and SIgA concentration were determined, and the SIgA secretion rate was calculated. The mean salivary SIgA secretion rate in the b240 group steadily increased until week 4 (exhibiting a 20% elevation relative to that at week 0), and then remained stable until week 12. Changes in SIgA secretion rate over the intervention period were significantly greater in the b240 group than in the placebo group. The treatment groups exhibited no significant differences in adverse events.</p> <p>Conclusions</p> <p>Oral intake of <it>L. pentosus </it>strain b240 for 12 weeks significantly accelerated salivary SIgA secretion, thereby indicating its potential utility in the improvement of mucosal immunity and resistance against infection in the elderly.</p

DNA-Free Recombinant SV40 Capsids Protect Mice from Acute Renal Failure by Inducing Stress Response, Survival Pathway and Apoptotic Arrest

Viruses induce signaling and host defense during infection. Employing these natural trigger mechanisms to combat organ or tissue failure is hampered by harmful effects of most viruses. Here we demonstrate that SV40 empty capsids (Virus Like Particles-VLPs), with no DNA, induce host Hsp/c70 and Akt-1 survival pathways, key players in cellular survival mechanisms. We postulated that this signaling might protect against organ damage in vivo. Acute kidney injury (AKI) was chosen as target. AKI is critical, prevalent disorder in humans, caused by nephrotoxic agents, sepsis or ischemia, via apoptosis/necrosis of renal tubular cells, with high morbidity and mortality. Systemic administration of VLPs activated Akt-1 and upregulated Hsp/c70 in vivo. Experiments in mercury-induced AKI mouse model demonstrated that apoptosis, oxidative stress and toxic renal failure were significantly attenuated by pretreatment with capsids prior to the mercury insult. Survival rate increased from 12% to >60%, with wide dose response. This study demonstrates that SV40 VLPs, devoid of DNA, may potentially be used as prophylactic agent for AKI. We anticipate that these finding may be projected to a wide range of organ failure, using empty capsids of SV40 as well as other viruses

Hemodialysis in children with ventriculoperitoneal shunts: prevalence, management and outcomes

Peer reviewe

IMPROVE-PD Finder: A Web-Based Platform to Search and Share Peritoneal Dialysis Biobank, Registry, and Clinical Trial Metadata

Peritoneal dialysis (PD) is a life-sustaining kidney replacement therapy for the increasing number of people with permanent kidney failure across all age groups worldwide. Although PD potentially offers socioeconomic and performance benefits over hemodialysis, both treatments severely accelerate complications of chronic kidney disease, in particular atherosclerotic disease progression that worsens outcomes when compared with non-dialysis patients.1 Improved understanding of the underlying molecular pathogenic mechanisms should help in the design of interventions that improve outcomes.2 Current state of the art in PD research, however, faces major limitations. Although there are numerous in vitro and ex vivo studies on complex cellular and molecular networks active in PD3, 4, 5 and in vivo animal models of PD6, 7, 8 that provide in-depth pathomechanistic insights and allow identification of promising therapeutic targets,9,S1,S2 translation into clinical studies is a major challenge.S3 Patient studies that aim to substantiate experimental findings with definitive clinical outcome data are mostly small. As a result, they have not provided sufficient power to derive meaningful or clinically implementable conclusions.2 Basic PD technique has hardly changed over decades, despite high PD-related complication rates. Randomized prospective trials with hard clinical end points studied with adequate power are difficult to realize in a multifactorial setting with low patient numbers (360,000 worldwide) and are associated with high costs. To overcome these barriers intermediate end points such as PD effluent biomarkers associated (but not necessarily causally related) with hard clinical end points and composite end points are often studied.S4,S5 Equally, combining analyses of existing cohort studies and trial data through collaborative sharing might be of considerable benefit

Clinical practice recommendations for native vitamin D therapy in children with chronic kidney disease Stages 2-5 and on dialysis

Vitamin D deficiency is widely prevalent and often severe in children and adults with chronic kidney disease (CKD). Although native vitamin D {25-hydroxyvitamin D [25(OH)D]} is thought to have pleiotropic effects on many organ systems, its skeletal effects have been most widely studied. The 25(OH)D deficiency is causally linked with rickets and fractures in healthy children and those with CKD, contributing to the CKD–mineral and bone disorder (MBD) complex. There are few studies to provide evidence for vitamin D therapy or guidelines for its use in CKD. A core working group (WG) of the European Society for Paediatric Nephrology (ESPN) CKD–MBD and Dialysis WGs have developed recommendations for the evaluation, treatment and prevention of vitamin D deficiency in children with CKD. We present clinical practice recommendations for the use of ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) in children with CKD Stages 2–5 and on dialysis. A parallel document addresses treatment recommendations for active vitamin D analogue therapy. The WG has performed an extensive literature review to include meta-analyses and randomized controlled trials in healthy children as well as children and adults with CKD, and prospective observational studies in children with CKD. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system has been used to develop and grade the recommendations. In the absence of applicable study data, the opinion of experts from the ESPN CKD–MBD and Dialysis WGs is provided, but clearly GRADE-ed as such and must be carefully considered by the treating physician, and adapted to individual patient needs as appropriate

Pediatr Nephrol

BACKGROUND: Current guidelines advocate use of arteriovenous fistula (AVF) over central venous catheter (CVC) for children starting hemodialysis (HD). European data on current practice, determinants of access choice and switches, patient survival, and access to transplantation are limited. METHODS: We included incident patients from 18 European countries who started HD from 2000 to 2013 for whom vascular access type was reported to the ESPN/ERA-EDTA Registry. Data were evaluated using descriptive statistics, logistic and Cox regression models, and cumulative incidence competing risk analysis. RESULTS: Three hundred ninety-three (55.1%) of 713 children started HD with a CVC and were more often females, younger, had more often an unknown diagnosis, glomerulonephritis, or vasculitis, and lower hemoglobin and height-SDS at HD initiation. AVF patients were 91% less likely to switch to a second access, and two-year patient survival was 99.6% (CVC, 97.2%). Children who started with an AVF were less likely to receive a living donor transplant (adjusted HR, 0.30; 95% CI, 0.16-0.54) and more likely to receive a deceased donor transplant (adjusted HR, 1.50; 95% CI, 1.17-1.93), even after excluding patients who died or were transplanted in the first 6 months. CONCLUSIONS: CVC remains the most frequent type of vascular access in European children commencing HD. Our results suggest that the choice for CVC is influenced by the time of referral, rapid onset of end-stage renal disease, young age, and an expected short time to transplantation. The role of vascular access type on the pattern between living and deceased donation in subsequent transplantation requires further study