Ten-year trends in epidemiology and outcomes of pediatric kidney replacement therapy in Europe : data from the ESPN/ERA-EDTA Registry

Background For 10 consecutive years, the ESPN/ERA-EDTA Registry has included data on children with stage 5 chronic kidney disease (CKD 5) receiving kidney replacement therapy (KRT) in Europe. We examined trends in incidence and prevalence of KRT and patient survival. Methods We included all children agedPeer reviewe

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

Induction of HSP 70 (heat shock 70 protein) in polymorphonyclear of septic neonates

Sepsis is one of the most common clinical syndromes among neonates admitted to the intensive care units. Despite more aggressive approaches to early diagnosis and the use of newer antibiotics and novel biotherapies, mortality rates remain elevated in almost all published series. This suggests that a better understanding of the pathogenesis of sepsis, as well as of the mechanisms implicated in this disorder, is required to establish more effective therapeutic tools. Heat shock proteins (Hsps) constitute a complex, broadly widespread and overarching basic cellular defense mechanism against numerous stresses. They are highly conserved in prokaryotes and eukaryotes cells. These proteins function as molecular chaperones to protect cells from environmental stress damage by binding to partially denatured proteins, dissociating protein aggregates, and regulating the correct folding and intracellular translocation of newly synthesized polypeptides. The exact mechanism through which stress provokes the induction of hsps has not yet been completely explored. Hsps are subdivided into five families, according to their molecular mass. So they are differentiated into families of 27, 40, 60, 70, 90 and 110 KDa. The most important hsp and best characterized, in the humans, is the hsp70. Hsps confer an advantage to the host. Recent reports have shown that the induction of hsp70 reduces the mortality rates from sepsis in several animal models. A very limited number of existing studies concern the induction of hsps in the human cells, all of which regard adults. The expression of hsp70 in human monocytes-macrophages under normal and after stressful circumstances has been identified. Human lymphocytes express hsp70 only under stressful situations. On the other hand human PMN produce hsp70 under normal conditions while under stress increase the hsp70 production. Recently an increase in expression of hsp70 in granulocytes of critically ill patients has been described as well as in monocytes and PMN of septic patients. To the best of our knowledge there is no relevant work concerning the expression of hsp70 in neonatal cells during sepsis. We recently have shown that PMN of healthy neonates displayed an increase of hsp70 after exposure to heat shock. In this study we examined the induction of hsp70 of neonates in sepsis. It is known that the PMN during sepsis play important role in host defense by way of their ability to release oxygen free radicals and many chemical mediators. It is also known that these mediators can have toxic effects not only on tissue cells but also on the PMN themselves. The induction of hsp70 in septic neonates, as a natural intracellular defense mechanism can contribute to the maintenance of PMN function that is their capacity to eliminate the invading microorganisms. The goal of this study was to examine and determine quantitatively: a) the spontaneous expression of hsp70 in PMN of neonates suffering from gram(-) sepsis. b) the induction of hsp70 in PMN of healthy neonates after incubation with LPS, FMLP, LPS and FMLP and to compare the hsp70 production between neonatal and adult PMN after an identical condition. Our interest in LPS, FMLP stems from the fact that they derive from Gram(-) bacteria which are known to be largely responsible for neonatal sepsis. c) the induction of hsp70 in PMN of healthy neonates and adults exposed to heat shock and to compare any difference between neonatal and adult PMNs. Hsp70 expression was detected by immunoblotting and was measured quantitatively by Densitometer. The results were analysed with Mann-Whitney test and Wilcoxon Signed Rank test according to indications. The comparison of the hsp70 induction in the PMN between three neonate groups was based on Kruskal-Wallis method. More specifically in this work the synthesis of hsp70 was measured in the following categories: 1) In PMN samples from 11 septic neonates, 12 hours after the diagnosis. We found that the PMN of these neonates express high levels of hsp70. The mean value of hsp70 was 2,04μγ/1500000 PMN (SD 1,54) while the mean value of PMN of healthy neonates, used as controls, was 0,53μγ/1500000 PMN (SD 0,36) p 0,05. The mean value of hsp70 of neonatal PMN was 0,53μγ/1500000 PMN (SD 0,24) [mean value of controls amounts to 0,51μγ/1500000 PMN, (SD 0,24)] and that of adult PMN was 0,39μγ/1500000 PMN (SD 0,11) [mean value of hsp70 of controls 0,33 μγ/1500000 PMN, (SD 0,18)]. We believe that the inability of PMN to increase the hsp70 production in vitro results from the fact that LPS only primes PMN activation when subsequently exposed to an agonist, e.g. formylpeptides. 3) In PMN samples from 12 healthy neonates and 12 adults incubated with FMLP (1μΜ for 4,5 h). On the adults PMN group, a significant increase in hsp70 levels was found in comparison with the one identified in healthy adult PMN not exposed to FMLP (controls), p 0,05. The mean value of hsp70 of healthy neonates activated with FMLP was 0,60μγ/1500000 PMN (SD 0,22) [mean value of hsp70 in controls 0,51μγ/1500000 PMN (SD 0,24)]. These findings suggest that hsp70 production in neonatal PMN after activation with FMLP is inferior to hsp70 production in adult PMN after FMLP activation. This is compatible with the known decreased chemotaxis of neonatal PMN to formylpeptides. 4) In PMN samples of 12 healthy neonates and 12 adults primed firstly with LPS (10ng/ml for 1h) and after activated with FMLP (1μΜ for 3,5h). The mean value of hsp70 in neonatal PMN was 0,66 μγ/1500000 PMN (SD 0,42) [the mean value of controls, that is healthy neonatal PMN not exposed to LPS and FMLP, was 0,51μγ/1500000 PMN (SD 0,24)] while the mean value of hsp70 in adults PMN was 0,54μγ/1500000 PMN (SD 0,23) [mean value of hsp70 of controls, that is healthy adults not exposed to LPS and then FMLP was 0,33 μγ/1500000 PMN (SD 0,18)]. It was found that neonatal PMN as well as adult PMN exposed to LPS and then to FMLP in vitro, displayed a significant increase in hsp70 production, p 0,05. 5) In PMN samples from 11 healthy neonates and 11 healthy adults exposed to heat shock in vitro (42°C for 1h). It was seen that neonatal and adult PMN showed an increase of hsp70 production, p 0,05 και για τις δυο ομάδες. Η μέση τιμή hsp70 για τα ΠΜΠ των νεογνών ήταν 0,53μγ/1500000 κύτταρα (SD 0,24) ενώ η μέση τιμή hsp70 στους μάρτυρες ήταν 0,51μγ/1500000 κύτταρα (SD 0,24). Για τα ΠΜΠ των ενηλίκων η μέση τιμή hsp 70 ήταν 0,39μγ/1500000 κύτταρα (SD 0,11) ενώ η μέση τιμή hsp70 στους μάρτυρες ήταν 0,33μγ/1500000 κύτταρα (SD 0,18). Θεωρούμε ότι η αδυναμία των ΠΜΠ τόσο των νεογνών όσο και των ενηλίκων να αυξήσουν την παραγωγή hsp70 μετά την επώαση με LPS in vitro οφείλεται στο γεγονός ότι το LPS απλώς πριμοδοτεί τα ΠΜΠ να ενεργοποιηθούν αποτελεσματικότερα όταν εκτεθούν σε κάποιον άλλο αγωνιστή π.χ. φορμυλπεπτίδια. 3. Σε δείγματα ΠΜΠ 12 υγιών νεογνών και 12 υγιών ενηλίκων που είχαν επωασθεί με FMLP in vitro (1μΜ για 4,5 ώρες). Στα ΠΜΠ των ενηλίκων που επωάσθηκαν με FMLP διαπιστώθηκε σημαντική αύξηση των επιπέδων hsp70 σε σχέση με αυτή που διαπιστώθηκε στα ΠΜΠ των υγιών ενηλίκων που δεν εκτέθηκαν σε FMLP (μάρτυρες), p 0.05. Η μέση τιμή hsp70 στα ΠΜΠ των υγιών νεογνών που ενεργοποιήθηκαν με FMLP ήταν 0,60μγ/1500000 κύτταρα (SD 0,22) ενώ η μέση τιμή hsp70 στα ΠΜΠ των μαρτύρων αντίστοιχα 0,51μγ/1500000 κύτταρα. (SD 0,24). Τα ευρήματα αυτά υποδηλώνουν ότι η παραγωγή hsp70 από τα νεογνικά ΠΜΠ μετά από διέγερση με φορμυλπεπτίδια υπολείπεται αυτής των ΠΜΠ των ενηλίκων, εύρημα συμβατό και με την γνωστή ελαττωμένη χημειοταξία των νεογνικών ΠΜΠ στα φορμυλπεπτίδια. 4. Σε δείγματα ΠΜΠ 12 υγιών νεογνών και 12 υγιών ενηλίκων που πριμοδοτήθηκαν πρώτα με LPS (10ng/ml για 1 ώρα) και στη συνέχεια ενεργοποιήθηκαν με FMLP (1μΜ για 3,5 ώρες ). Διαπιστώθηκε ότι όταν εκτέθηκαν σε συνδυασμό LPS και FMLP in vitro, τόσο τα νεογνικά ΠΜΠ όσο και τα ΠΜΠ των ενηλίκων παρουσίασαν σημαντική αύξηση της παραγωγής hsp70. p 0,05. 5. Σε δείγματα ΠΜΠ 11 υγιών νεογνών και 11 υγιών ενηλίκων που εκτεθήκαν σε θερμικό stress in vitro (στους 42°C για 1 ώρα). Διαπιστώθηκε ότι τα ΠΜΠ των υγιών νεογνών που εκτέθηκαν σε θερμικό stress παρουσίασαν αύξηση της παραγωγής hsp70 η οποία δεν διέφερε ουσιαστικά από την ανάλογη παραγωγή των ΠΜΠ των ενηλίκων που εκτέθηκαν στις ίδιες συνθήκες stress. p < 0,01 και p = 0,012 για τα νεογνά και τους ενήλικες αντίστοιχα. Η μέση τιμή hsp70 στα νεογνικά ΠΜΠ που εκτέθηκαν σε θερμικό stress (42°C για 1 ώρα) ήταν 1,02μγ/1500000 κύτταρα (SD 0,36) ενώ η μέση τιμή hsp70 στα ΠΜΠ των νεογνών που παρέμειναν στους 37 °C ήταν 0,53μγ/1500000 (SD 0,36) κύτταρα. Η μέση τιμή hsp70 στα ΠΜΠ των ενηλίκων ήταν 0,57μγ/1500000 κύτταρα (SD 0,42) ενώ η μέση τιμή hsp70 στα ΠΜΠ των μαρτύρων 0,35μγ/1500000 κύτταρα (SD 0,22). 6. Συγκρίνοντας τις 3 ομάδες νεογνών (σηπτικά, υγιή νεογνά που εκτέθηκαν σε θερμικό stress και υγιή νεογνά που επωάσθηκαν πρώτα με LPS και στη συνέχεια με FMLP) βρέθηκε ότι η παραγωγή hsp70 στα ΠΜΠ των σηπτικών νεογνών είναι σημαντικά μεγαλύτερη από αυτή που παρατηρείται στα ΠΜΠ των υγιών νεογνών που εκτέθηκαν σε θερμικό stress in vitro ή επωάσθηκαν με LPS και FMLP. p < 0,01. Αυτό υποδηλώνει ότι η φλεγμονώδης απάντηση στη σήψη είναι σύνθετη και εμπλέκονται σε αυτή και πολλοί άλλοι παράγοντες εκτός του LPS, FMLP και της υπερθερμίας. Συμπερασματικά από τη μελέτη μας προκύπτει ότι τα νεογνικά ΠΜΠ παράγουν αυτόματα μεγάλες ποσότητες hsp70 κατά τη διάρκεια της σήψης. Το γεγονός αυτό επιβεβαιώθηκε και in vitro όπου διαπιστώθηκε παραγωγή hsps στα ΠΜΠ του νεογνού μετά την επίδραση LPS και FMLP. Εντούτοις παρά το γεγονός ότι διαθέτουν τον προστατευτικό μηχανισμό των hsps, ο μηχανισμός αυτός δεν φαίνεται να επαρκεί για να τα προφυλάξει από την αυξημένη θνητότητα κατά τη διάρκεια της σήψης. Είναι ευνόητο ότι χρειάζεται περισσότερη έρευνα για να αυξήσουμε τις γνώσεις μας όσον αφορά στο μηχανισμό με τον οποίο δρουν οι hsps κατά τη διάρκεια της σήψης. Θεωρούμε ότι με αυτό τον τρόπο θα έχουμε κάνει ένα σημαντικό βήμα στο δρόμο για την απόκτηση νέων αποτελεσματικότερων θεραπευτικών μέσων για την επιτυχή αντιμετώπιση της νεογνικής σήψης

The immunopathogenesis of idiopathic nephrotic syndrome: a narrative review of the literature

Idiopathic nephrotic syndrome (INS) is a common glomerular disease in childhood, and the immunological involvement in the pathogenesis of non-genetic INS, although not fully elucidated, is evident. This narrative review aims to offer a concise and in-depth view of the current knowledge on the immunological mechanisms of the development of INS as well as the role of the immunological components of the disease in the responsiveness to treatment. T cell immunity appears to play a major role in the INS immunopathogenesis and has been the first to be linked to the disease. Various T cell immunophenotypes are implicated in INS, including T-helper-1, T-helper-2, T-helper-17, and T regulatory cells, and various cytokines have been proposed as surrogate biomarkers of the disease; however, no distinct T helper or cytokine profile has been conclusively linked to the disease. More recently, the recognition of the role of B cell mediated immunity and the various B cell subsets that are dysregulated in patients with INS have led to new hypotheses on the underlying immunological causes of INS. Finally, the disambiguation of the exact mechanisms of the INS development in the future may be the key to the development of more targeted personalized approaches in managing INS. Conclusions: INS demonstrates particularly interesting immunopathogenetic pathways, in which multiple interactions between T cell and B cell immunity and the podocyte are involved. The disambiguation of these pathways will provide promising novel therapeutic targets in INS. What is Known: INS is the most common glomerular disease in the paediatric population, and its onset and relapses have been linked to various immunological triggers. Multiple immunological mechanisms have been implicated in the pathogenesis of INS; however, no single distinct immunological profile has been recognized. What is New: Th17 cells and Treg cells play an important role in the immune dysregulation in INS. Transitional B cell levels as well as the transitional/memory B cell ratio have been correlated to nephrotic relapses and have been proposed as biomarkers of INS relapses in SSNS patients

HAEMODIAFILTRATION (HDF) IS ASSOCIATED WITH SUPERIOR FLU ID CONTROL AND REDUCED CARDIOVASCULAR RISK PROFILE COMPARED TO CONVENTIONAL HAEMODIALYSIS (HD) - DATA FROM THE HDF VS HD (3H) STUDY

WOS: 000408418900275

EFFECTS OF HAEMODIAFILTRATION (HDF) VS CONVENTIONAL HAEMODIALYSIS (HD) ON GROWTH AND CARDIOVASCULAR MARKERS IN CHILDREN - DATA FROM THE HDF VS HD (3H) STUDY

WOS: 000408418900034

HAEMODIAFILTRATION (HDF) IMPROVES THE CARDIOVASCULAR RISK PROFILE COMPARED TO CONVENTIONAL HAEMODIALYSIS (HD) THROUGH IMPROVED BP AND PTH CONTROL - THE HDF, HEART AND HEIGHT (3H) TRIAL

WOS: 000443998400060

Safety and immunogenicity of booster immunization with 7-valent pneumococcal conjugate vaccine in children with idiopathic nephrotic syndrome

Safety and immunogenicity of a booster dose of 7-valent pneumococcal conjugate vaccine (PCV7) were evaluated in 29 patients with idiopathic nephrotic syndrome (INS), who had been primed 12 months earlier with one dose of PCV7. PCV7 was not associated with increased risk of INS relapse (RR = 0.77, p = 0.8) and serotype-specific antibodies increased in all subjects at 1 month (p &lt; 0.01). The quantitative characteristics of immune response and the effect of treatment with mycophenolate mofetil and/or cyclosporine A following booster PCV7 were similar with primary response. Additional PCV7 doses could be safely given in children with INS to increase circulating antibodies above the protective threshold. (C) 2014 Elsevier Ltd. All rights reserved