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ADAMTS13 (A Disintegrin and Metalloprotease with ThromboSpondin type 1 motifs) activity is a key tool in differential diagnosis of thrombotic microangiopathies (TMAs). Due to the lack of availability of ADAMTS13 testing, PLASMIC/PLASIC scores have been suggested to predict ADAMTS13 deficiency. The importance of differentiating TTP from other complement-mediated TMAs is highlighted by the need to urgently start plasma exchange and utility of treatments such as caplacizumab or eculuzimab. Therefore, we aimed to evaluate ADAMTS13 activity, PLASMIC/PLASIC scores, and complement testing in guiding management of a real-world TMA cohort. We enrolled consecutive TMA patients with samples referred to our Center (01/2018–2020). If ADAMTS13 ​> ​10%, soluble C5b-9 was measured. Among 80 TMA patients, ADAMTS13 activity was ≤10% in 50 patients, while 28 had a relapsing disease. PLASMIC/PLASIC were excellent predictors of ADAMTS13 deficiency, especially in patients without secondary causes. Soluble C5b-9 levels were elevated (median 525 ​ng/ml, range 313–913 ​ng/ml) in 7 patients without secondary causes and ADAMTS13 ​> ​10% (hemolytic uremic syndrome/HUS). Two were shiga-toxin associated; while 5 atypical HUS. Only 1/5 patients received eculizumab and achieved TMA resolution implemented by guidance based on soluble C5b-9 levels. In transplant-associated TMA, 8/16 patients not responding to first-line treatment received eculizumab due to elevated C5b-9 levels (median 353 ​ng/ml, range 281–1252 ​ng/ml) and achieved TMA resolution. In conclusion, our real-world data confirm that ADAMTS13, complement testing, and PLASMIC/PLASIC are valuable tools in diagnosis and management of TMAs, but also highlight the unmet need of using available markers and treatments in clinical practice. © 2021

Shroff, Rukshana C/0000-0001-8501-1072; /0000-0001-8501-1072; Caliskan, Salim/0000-0002-3316-8032; Dufek, Stephanie/0000-0002-6323-6673; Verrina, Enrico Eugenio/0000-0002-5178-1949; pasini, andrea/0000-0001-8479-8379; Faria, Maria do Sameiro/0000-0002-8061-9289; Bacchetta, Justine/0000-0002-0578-2529 WOS:000459819600014 PubMed ID: 30374605 BackgroundChildren with congenital nephrotic syndrome (CNS) commonly develop end stage renal failure in infancy and require dialysis, but little is known about the complications and outcomes of dialysis in these children.MethodsWe conducted a retrospective case note review across members of the European Society for Pediatric Nephrology Dialysis Working Group to evaluate dialysis management, complications of dialysis, and outcomes in children with CNS.ResultsEighty children (50% male) with CNS were identified form 17 centers over a 6-year period. Chronic dialysis was started in 44 (55%) children at a median age of 8 (interquartile range 4-14) months. Of these, 17 (39%) were on dialysis by the age of 6months, 30 (68%) by 1year, and 40 (91%) by 2years. Peritoneal dialysis (PD) was the modality of choice in 93%, but 34% switched to hemodialysis (HD), largely due to catheter malfunction (n=5) or peritonitis (n=4). The peritonitis rate was 0.77 per patient-year. Weight and height SDS remained static after 6months on dialysis. In the overall cohort, at final follow-up, 29 children were transplanted, 18 were still on dialysis (15 PD, 3 HD), 19 were in pre-dialysis chronic kidney disease (CKD), and there were 14 deaths (8 on dialysis). Median time on chronic dialysis until transplantation was 9 (6-18) months, and the median age at transplantation was 22 (14-28) months.ConclusionsInfants with CNS on dialysis have a comparable mortality, peritonitis rate, growth, and time to transplantation as infants with other primary renal diseases reported in international registry data. Department of Health [CDF-2016-09-038] Funding Source: Medline

Achieving normal growth is one of the most challenging problems in the management of children with chronic kidney disease (CKD). Treatment with recombinant human growth hormone (GH) promotes longitudinal growth and likely enables children with CKD and short stature to reach normal adult height. Here, members of the European Society for Paediatric Nephrology (ESPN) CKD–Mineral and Bone Disorder (MBD), Dialysis and Transplantation working groups present clinical practice recommendations for the use of GH in children with CKD on dialysis and after renal transplantation. These recommendations have been developed with input from an external advisory group of paediatric endocrinologists, paediatric nephrologists and patient representatives. We recommend that children with stage 3–5 CKD or on dialysis should be candidates for GH therapy if they have persistent growth failure, defined as a height below the third percentile for age and sex and a height velocity below the twenty-fifth percentile, once other potentially treatable risk factors for growth failure have been adequately addressed and provided the child has growth potential. In children who have received a kidney transplant and fulfil the above growth criteria, we recommend initiation of GH therapy 1 year after transplantation if spontaneous catch-up growth does not occur and steroid-free immunosuppression is not a feasible option. GH should be given at dosages of 0.045–0.05 mg/kg per day by daily subcutaneous injections until the patient has reached their final height or until renal transplantation. In addition to providing treatment recommendations, a cost-effectiveness analysis is provided that might help guide decision-making., This Evidence-Based Guideline developed by members of the European Society for Paediatric Nephrology CKD-MBD, Dialysis and Transplantation working groups presents clinical practice recommendations for the use of growth hormone in children with chronic kidney disease on dialysis and after renal transplantation.

BackgroundThere are three principle forms of vascular access available for the treatment of children with end stage kidney disease (ESKD) by haemodialysis: tunnelled catheters placed in a central vein (central venous lines, CVLs), arteriovenous fistulas (AVF), and arteriovenous grafts (AVG) using prosthetic or biological material. Compared with the adult literature, there are few studies in children to provide evidence based guidelines for optimal vascular access type or its management and outcomes in children with ESKD.MethodsThe European Society for Paediatric Nephrology Dialysis Working Group (ESPN Dialysis WG) have developed recommendations for the choice of access type, pre-operative evaluation, monitoring, and prevention and management of complications of different access types in children with ESKD.ResultsFor adults with ESKD on haemodialysis, the principle of “Fistula First” has been key to changing the attitude to vascular access for haemodialysis. However, data from multiple observational studies and the International Paediatric Haemodialysis Network registry suggest that CVLs are associated with a significantly higher rate of infections and access dysfunction, and need for access replacement. Despite this, AVFs are used in only ∼25% of children on haemodialysis. It is important to provide the right access for the right patient at the right time in their life-course of renal replacement therapy, with an emphasis on venous preservation at all times. While AVFs may not be suitable in the very young or those with an anticipated short dialysis course before transplantation, many paediatric studies have shown that AVFs are superior to CVLs.ConclusionsHere we present clinical practice recommendations for AVFs and CVLs in children with ESKD. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system has been used to develop and GRADE the recommendations. In the absence of high quality evidence, the opinion of experts from the ESPN Dialysis WG is provided, but is clearly GRADE-ed as such and must be carefully considered by the treating physician, and adapted to local expertise and individual patient needs as appropriate.

Molecular diagnosis is a useful diagnostic tool in primary nephrogenic diabetes insipidus (NDI), an inherited disease characterized by renal inability to concentrate urine. The AVPR2 and AQP2 genes were screened for mutations in a cohort of 25 patients with clinical diagnosis of NDI. Patients presented with dehydration, polyuria-polydipsia, failure to thrive (mean ± SD; Z-height -1.9 ± 2.1 and Z-weight -2.4 ± 1.7), severe hypernatremia (mean ± SD; Na 150 ± 10 mEq/L), increased plasma osmolality (mean ± SD; 311 ± 18 mOsm/Kg), but normal glomerular filtration rate. Genetic diagnosis revealed that 24 male patients were hemizygous for 17 different putative disease-causing mutations in the AVPR2 gene (each one in a different family). Of those, nine had not been previously reported, and eight were recurrent. Moreover, we found those same AVPR2 changes in 12 relatives who were heterozygous carriers. Further, in one female patient, AVPR2 gene study turned out to be negative and she was found to be homozygous for the novel AQP2 p.Ala86Val alteration.Genetic analysis presumably confirmed the diagnosis of nephrogenic diabetes insipidus in every patient of the studied cohort. We emphasize that we detected a high presence (50 %) of heterozygous females with clinical NDI symptoms.• In most cases (90 %), inherited nephrogenic diabetes insipidus (NDI) is an X-linked disease, caused by mutations in the AVPR2 gene. • In rare occasions (10 %), it is caused by mutations in the AQP2 gene. What is new: • In this study, we report 10 novel mutations associated with NDI. • We have detected a high presence (50 %) of heterozygous carriers with clinical NDI symptoms.

PubMedID: 28873971 In patients with chronic kidney disease (CKD), renal synthesis of active Vitamin D [1, 25-dihydroxyVitamin D (1, 25(OH)2D)] declines and is associated with hypocalcaemia, secondary hyperparathyroidism and the spectrum of CKD-mineral and bone disorder (MBD). In advanced CKD, active Vitamin D analogues, including alfacalcidol, calcitriol and paricalcitol, are routinely administered. There are few studies on the use of Vitamin D analogues in children with CKD and on dialysis. It is difficult to define bone-specific outcomes that can guide treatment with active Vitamin D analogues in children with CKD-MBD. A core working group (WG) of the European Society for Paediatric Nephrology (ESPN) CKD-MBD and Dialysis WGs has developed recommendations for the use of active Vitamin D therapy in children with CKD and on dialysis. A second document in parallel with this one covers treatment recommendations for native Vitamin D therapy. The WGs have performed an extensive literature review to include systematic reviews and randomized controlled trials in adults and children with CKD and prospective observational studies in children with CKD. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system was 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. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. National Institute for Health Research RS holds a fellowship with the National Institute for Health Research (NIHR). Members of the ESPN CKD-MBD Working Group: Belgium: A. Prytula, Ghent University, Utopaed. France: J. Bachetta., University Children’s Hospital, Lyon. Germany: D. Haffner., Hannover Medical School, Hannover. G. Klaus, University Children’s Hospital, Marburg. Hungary: G. Reusz, Semmelweis University, Budapest. Italy: E. Verrina, G. Gaslini Institute, Genoa. The Netherlands: J. Groothoff, Academic Medical Center, Amsterdam. Spain: M.A. Gamero, Reina Sofía Universitary Hospital, Córdoba. Russia: E. Petrosyan, Russian National Research Medical University, Moscow. Turkey: S. A. Bakkaloglu, Gazi University Hospital, Ankara; I. Dursun, Erciyes University Faculty of Medicine, Kayseri. United Kingdom: R. Shroff, Great Ormond Street Hospital, London. Members of the ESPN Dialysis Working Group: Austria: C. Aufricht, Medical University of Vienna, Vienna. Belgium: J. Vande Walle, University Hospital Ghent, Department of Pediatric Nephrology/Urology, Ghent. Czech Republic: K. Vondrak, University Hospital Motol, Charles University Prague, 2nd Faculty of Medicine, Prague. Finland: T. Holtta, Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki. France: B. Ranchin, Centre de Référence des Maladies Rénales Héréditaires, Hospices Civils de Lyon and Université Lyon, Lyon. M. Fischbach, Hautepierre University Hospital, Strasbourg. Germany: Claus Peter Schmitt, University of Heidelberg, Heidelberg. Günter Klaus, University Children’s Hospital, Marburg. Greece: Constantinos J. Stefanidis, A. and P. Kyriakou Childrens Hospital, Athens; N. Printza, Aristotle University of Thessaloniki, Thessaloniki. Italy: Alberto Edefonti, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan; E. Verrina, Giannina Gaslini Children’s Hospital, Dialysis Unit, Genova; E. Vidal, University Hospital of Padova, Padova. Lithuania: A. Jankauskiene, Vilnius

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Nephroblastomatosis (NB) has been considered as a precursor of Wilms tumor (WT). The natural history of NB seems to present significant variation as some lesions may regress spontaneously, while others may grow and expand or relapse and develop into WT later in childhood. Although, most investigators suggest adjutant chemotherapy, the effect and duration of treatment are not well established. Children with diffuse perilobar NB, Beckwith-Wiedemann syndrome, and hemihypertrophy seem to particularly benefit from treatment. We discuss our experience on two cases of NB and we review the literature for the management of this rare condition.

Little information exists regarding the efficacy, modifiers, and outcomes of anemia management in children with CKD or ESRD. We assessed practices, effectors, and outcomes of anemia management in 1394 pediatric patients undergoing peritoneal dialysis (PD) who were prospectively followed in 30 countries. We noted that 25% of patients had hemoglobin levels below target (

Peritoneal dialysis (PD) is an established, effective long term renal replacement treatment modality for children with end stage renal disease (ESRD). A rarely reported complication of PD in children is the development of hydrothorax1. We report the case of an 8-year-old boy that developed a right-sided pleural effusion during automated PD (APD), in order to raise awareness amongst paediatricians; we also review the diversity of clinical presentation and the available diagnostic tools, discuss theories regarding aetiology and highlight the available treatment options.

The contribution of renal biopsy is of major importance in many renal diseases in children. In our study we aimed to evaluate retrospectively the indications, safety, efficacy and the spectrum of histopathological findings of percutaneous ultrasound-guided renal (PRB) biopsy during a 7 year period as well as to analyze specific groups of renal patients.A total of 84 renal biopsies were performed in 81 children. Demographic data, clinical symptoms at presentation, indications for renal biopsy, laboratory findings, complications of the procedure and histological diagnosis were obtained from all patients who underwent PRB.The commonest indication for biopsy accounted was steroid resistant, steroid dependent or frequent relapsing idiopathic nephrotic syndrome (INS). Subcapsular hematoma presented 11% of the patients, but none of them needed blood transfusion. Adequate renal tissue sample was obtained in 97.7% of the renal biopsies. In 80% the histopathology revealed glomerular diseases. The most frequent types of biopsy-proven renal diseases were: focal segmental glomerulosclerosis (FSGS) (15%), IgA nephropathy (13.5%), minimal change disease (10%), various stages of lupus nephritis (8.5%), Henoch-Schonlein nephritis (7.5%), membranous glomerulonephritis (7.5%), mesangioproliferative glomerulonephritis (6%), post-infectious glomerulonephritis (6%), hemolytic uremic syndrome (5%), tubulointerstitial nephropathies (3.5%), acute tubular necrosis 2.5%. Among the 28 cases of INS, FSGS accounted for 43%. The leading histopathological pattern found in patients with recurrent episodes of gross haematuria was IgAN (84.5%). Among 7 cases of lupus nephritis, the observed histological types were: IV+V in 3/7, IIIA in 3/7 (43%) and IIB in 1/7.Our study shows that percutaneous ultrasound-guided renal biopsy is a safe, reliable and effective technique in children. It also provides updated information for childhood renal disease pattern.

Prader - Willi syndrome (PWS) is a neurobehavioral disorder characterized mainly by neonatal hypotonia, dysmorphic features, hypogonadism, mental retardation and behavioral problems. The PWS has not been associated with renal complications. We report the case of an infant with Prader-Willi syndrome due to loss of the paternal copy of chromosome 15q11.2-13, who presented with severe proteinuria and microscopic hematuria. Renal biopsy revealed mesangioproliferative glomerulonephritis (MPGN). The early onset of the primary MPGN in this infant make us consider a possible association between the deficiency of the paternally expressed genes from the 15q11-q13 region and the renal disease.

We present a 7-year old girl with severe urolithiasis due to cystinouria. Medical treatment after the surgical procedures was initiated with intensive hydration, urine alkalinisation and captopril. We discuss the therapeutic efficacy of captopril in resolving lithiasis as well as in preventing new stone formation.