Pediatr Nephrol

BACKGROUND: Hemolytic uremic syndrome due to Shiga toxin-producing E. coli (STEC-HUS) is the main cause of acute kidney injury in young children. Most fully recover kidney function; however, some develop long-term sequelae. We aimed to determine whether kidney injury 1 year after HUS onset is associated with long-term kidney outcome in pediatric STEC-HUS. METHODS: A retrospective population-based study of children /= 1 signs of kidney injury. Data from 81 patients were collected after median follow-up of 8.7 (IQR 3.5-12.7) years. At last follow-up, 42 (44% of survivors) had >/= 1 signs of kidney injury including decreased estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m(2) (n = 30), proteinuria (n = 17), or hypertension (n = 5). Among 42 patients with kidney injuries at 1-year follow-up, only 22 (52%) still had kidney disease at last follow-up. Conversely, of 33 patients without kidney injury at 1-year and available long-term outcome data, 11 (33%) had proteinuria or decreased GFR at last follow-up. There was no statistically significant association between kidney injury at 1 year and long-term kidney outcome. CONCLUSIONS: Since kidney sequelae may appear at variable time intervals after acute HUS, all patients need lifelong follow-up to detect early signs of chronic kidney disease and propose measures to slow progression

Nephrol Dial Transplant

BACKGROUND: Treatment with eculizumab in Shiga toxin-associated haemolytic and uraemic syndrome (STEC-HUS) remains controversial despite its increasing utilization. The aim of our study was to evaluate the outcomes of children treated with eculizumab for STEC-HUS in a single-centre matched cohort study. METHODS: Data were retrospectively collected from medical records of children diagnosed with STEC-HUS. The outcomes of patients treated with eculizumab for STEC-HUS were compared with those of a control group of untreated patients matched for age, sex and severity of acute kidney injury with a 1:2 matching scheme. RESULTS: Eighteen children (median age 40.6 months) with STEC-HUS treated with eculizumab were compared with 36 matched control patients (median age 36.4 months) who did not receive eculizumab. All patients survived in the two groups. Within 1 month of HUS onset, the evolution of haematological and renal parameters did not differ between the two groups. At 12 months of follow-up, renal outcome was not significantly different between the two groups. At the last follow-up, the prevalence of decreased glomerular filtration rate in the eculizumab group (27%) was not statistically different from that in controls (38%), as was the prevalence of proteinuria and high blood pressure. Children who received eculizumab more often had extrarenal sequelae during follow-up. Eculizumab treatment appeared to be safe in children with STEC-HUS. CONCLUSION: The benefit of eculizumab on renal and extrarenal outcomes in STEC-HUS could not be established based on our findings. However, efficacy and safety are not best assessed by the observational design and small sample size of our study. Randomized controlled trials are thus required to determine the efficacy of eculizumab in this indication

Pediatr Nephrol

BACKGROUND: Hemolytic uremic syndrome (HUS) has been associated with a number of infectious agents. We report here the case of an infant with severe Bordetella pertussis infection who developed HUS. CASE DIAGNOSIS/TREATMENT: A 2-month-old preterm male was admitted for severe Bordetella pertussis infection. Symptoms leading to a diagnosis of hemolytic uremic syndrome (HUS) rapidly appeared: hemolytic anemia, thrombocytopenia, and acute kidney injury. He was treated with 25 days of peritoneal dialysis and received complement-targeting therapy with eculizumab (five injections over 2 months), in addition to blood transfusions, antibiotics, and respiratory support. The outcome was favorable. The genetic workup found a complement factor H gene variant which has been associated with atypical HUS. This variant was located in the C3b-binding site and functional tests revealed that it perturbed the regulatory activity of factor H. CONCLUSION: This case suggests that pertussis is a strong trigger of HUS and that complement investigations are necessary to guide treatment and understand the pathophysiology

ADPedKD: A Global Online Platform on the Management of Children With ADPKD

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of renal failure. For several decades, ADPKD was regarded as an adult-onset disease. In the past decade, it has become more widely appreciated that the disease course begins in childhood. However, evidence-based guidelines on how to manage and approach children diagnosed with or at risk of ADPKD are lacking. Also, scoring systems to stratify patients into risk categories have been established only for adults. Overall, there are insufficient data on the clinical course during childhood. We therefore initiated the global ADPedKD project to establish a large international pediatric ADPKD cohort for deep characterization. Methods: Global ADPedKD is an international multicenter observational study focusing on childhooddiagnosed ADPKD. This collaborative project is based on interoperable Web-based databases, comprising 7 regional and independent but uniformly organized chapters, namely Africa, Asia, Australia, Europe, North America, South America, and the United Kingdom. In the database, a detailed basic data questionnaire, including genetics, is used in combination with data entry from follow-up visits, to provide both retrospective and prospective longitudinal data on clinical, radiologic, and laboratory findings, as well as therapeutic interventions. Discussion: The global ADPedKD initiative aims to characterize in detail the most extensive international pediatric ADPKD cohort reported to date, providing evidence for the development of unified diagnostic, follow-up, and treatment recommendations regarding modifiable disease factors. Moreover, this registry will serve as a platform for the development of clinical and/or biochemical markers predicting the risk of early and progressive disease

Treatment and long-term outcome in primary distal renal tubular acidosis

Background Primary distal renal tubular acidosis (dRTA) is a rare disorder, and we aimed to gather data on treatment and long-term outcome.Methods We contacted paediatric and adult nephrologists through European professional organizations. Responding clinicians entered demographic, biochemical, genetic and clinical data in an online form.Results Adequate data were collected on 340 patients (29 countries, female 52%). Mutation testing had been performed on 206 patients (61%); pathogenic mutations were identified in 170 patients (83%). The median (range) presentation age was 0.5 (0-54) years and age at last follow-up was 11.0 (0-70.0) years. Adult height was slightly below average with a mean (SD score) of -0.57 (1.16). There was an increased prevalence of chronic kidney disease (CKD) Stage 2 in children (35%) and adults (82%). Nephrocalcinosis was reported in 88%. Nephrolithiasis was more common with SLC4A1 mutations (42% versus 21%). Thirty-six percent had hearing loss, particularly in ATP6V1B1 (88%). The median (interquartile range) prescribed dose of alkali (mEq/kg/day) was 1.9 (1.2-3.3). Adequate metabolic control (normal plasma bicarbonate and normocalciuria) was achieved in 158 patients (51%), more commonly in countries with higher gross domestic product (67% versus 23%), and was associated with higher height and estimated glomerular filtration rate.Conclusion Long-term follow-up from this large dRTA cohort shows an overall favourable outcome with normal adult height for most and no patient with CKD Stage 5. However, 82% of adult patients have CKD Stages 2-4. Importance of adequate metabolic control was highlighted by better growth and renal function but was achieved in only half of patients.C1 [Lopez-Garcia, Sergio Camilo; Kleta, Robert; Bockenhauer, Detlef] NHS Fdn Trust, Great Ormond St Hosp Children, Dept Paediat Nephrol, London, England.[Lopez-Garcia, Sergio Camilo; Walsh, Stephen B.; Dufek, Stephanie; Iancu, Daniela; Kleta, Robert; Bockenhauer, Detlef] UCL, Ctr Nephrol, London, England.[Walsh, Stephen B.] Bambino Gesu Childrens Hosp IRCCS, Div Nephrol, Rome, Italy.[Fila, Marc] Montpellier Univ Hosp, CHU Arnaud Villeneuve, Pediat Nephrol, Montpellier, France.[Hooman, Nakysa] Iran Univ Med Sci, Ali Asghar Clin Res Dev Ctr, Tehran, Iran.[Zaniew, Marcin] Univ Zielona Gora, Dept Pediat, Zielona Gora, Poland.[Bertholet-Thomas, Aurelia] Ctr Reference Malad Renales Rares, Bron, France.[Colussi, Giacomo] ASST Niguarda, Milan, Italy.[Burgmaier, Kathrin] Univ Hosp Cologne, Dept Pediat, Cologne, Germany.[Levtchenko, Elena] Univ Hosp Leuven, Leuven, Belgium.[Sharma, Jyoti; Singhal, Jyoti] King Edward Mem Hosp, Pune, Maharashtra, India.[Soliman, Neveen A.] Cairo Univ, Dept Pediat, Ctr Pediat Nephrol & Transplantat, Kasr Al Ainy Sch Med, Cairo, Egypt.[Ariceta, Gema] Hosp Univ Vall dHebron, Barcelona, Spain.[Basu, Biswanath] NRS Med Coll, Div Pediat Nephrol, Kolkata, India.[Murer, Luisa] Azienda Osped & Univ Padova, Pediat Nephrol Dialysis & Transplant Unit, Padua, Italy.[Tasic, Velibor] Univ Childrens Hosp, Med Sch, Skopje, Macedonia.[Tsygin, Alexey] Natl Med & Res Ctr Childrens Hlth, Moscow, Russia.[Decramer, Stephane] CHU Toulouse, Serv Nephrol Pediat, Hop Enfants, Ctr Reference Malad Renales Rares Sud Ouest, Toulouse, France.[Gil-Pena, Helena] Hosp Univ Cent Asturias, Oviedo, Spain.[Koster-Kamphuis, Linda] Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands.[La Scola, Claudio] Azienda Osped Univ St Orsola Malpighi, Nephrol & Dialysis Unit, Dept Woman Child & Urol Dis, Bologna, Italy.[Gellermann, Jutta; Thumfart, Julia] Charite Univ Med Berlin, Berlin, Germany.[Konrad, Martin; Koenig, Jens] Univ Childrens Hosp, Munster, Germany.[Lilien, Marc] Univ Med Ctr, Wilhelmina Childrens Hosp, Utrecht, Netherlands.[Francisco, Telma] Ctr Hosp Lisboa Cent, Lisbon, Portugal.[Tramma, Despoina] Aristotle Univ Thessaloniki, Pediat Dept 4, Thessaloniki, Greece.[Trnka, Peter] Lady Cilento Childrens Hosp, Brisbane, Qld, Australia.[Trnka, Peter; Mallett, Andrew] Univ Queensland, Sch Med, Brisbane, Qld, Australia.[Yuksel, Selcuk] Pamukkale Univ, Dept Pediat Nephrol, Sch Med, Denizli, Turkey.[Caruso, Maria Rosa] Azienda Osped Papa Giovani XXIII, Nephrol Unit, Bergamo, Italy.[Chromek, Milan] Lund Univ, Karolinska Inst, Lund, Sweden.[Ekinci, Zelal] Grp Florence Nightingale Hosp, Istanbul, Turkey.[Gambaro, Giovanni] Univ Cattolica Sacro Cuore, Fdn Policlin A Gemelli, Rome, Italy.[Kari, Jameela A.] King Abdulaziz Univ, Pediat Nephrol Ctr Excellence, Fac Med, Jeddah, Saudi Arabia.[Kari, Jameela A.] King Abdulaziz Univ, Pediat Dept, Fac Med, Jeddah, Saudi Arabia.[Taroni, Francesca] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Pediat Nephrol Dialysis & Transplant Unit, Milan, Italy.[Trepiccione, Francesco] Univ Campania L Vanvitelli, Dept Translat Med Sci, Naples, Italy.[Winding, Louise] Lillebaelt Hosp Kolding, Pediat Dept, Kolding, Denmark.[Wuehl, Elke; Schaefer, Franz] Univ Hosp Heidelberg, Div Pediat Nephrol, Ctr Pediat & Adolescent Med, Heidelberg, Germany.[Agbas, Ayse] Haseki Educ & Res Hosp, Istanbul, Turkey.[Belkevich, Anna] Belarusian State Med Univ, Minsk, BELARUS.[Vargas-Poussou, Rosa; Blanchard, Anne] Hop Europeen Georges Pompidou, AP HP, Dept Genet, Paris, France.[Conti, Giovanni] AOU Policlin G Martino, Pediat Nephrol Unit, Messina, Italy.[Boyer, Olivia] Hop Necker Enfants Malad, Paris, France.[Dursun, Ismail; Pinarbasi, Ayse Seda] Erciyes Univ, Dept Pediat Nephrol, Fac Med, Kayseri, Turkey.[Melek, Engin] Cukurova Univ, Adana, Turkey.[Miglinas, Marius] Vilnius Univ, Nephrol Ctr, Santaros Klin, Vilnius, Lithuania.[Novo, Robert] Univ Hosp Lille, Lille, France.[Mallett, Andrew] Royal Brisbane & Womens Hosp, Dept Renal Med, Brisbane, Qld, Australia.[Milosevic, Danko] Univ Hosp Ctr Zagreb, Zagreb, Croatia.[Szczepanska, Maria] SUM Katowice, Dept Pediat, SMDZ Zabrze, Katowice, Poland.[Wente, Sarah] Hannover Med Sch, Dept Pediat Nephrol, Hannover, Germany.[Cheong, Hae Il] Seoul Univ, Dept Pediat, Childrens Hosp, Seoul, South Korea.[Sinha, Rajiv] Inst Child Hlth, Kolkata, India.[Gucev, Zoran] Univ Childrens Hosp, Med Sch, Skopje, Macedonia.[Peco-Antic, Amira] Univ Childrens Hosp, Dept Nephrol, Belgrade, Serbia.[Kaur, Amrit] Royal Manchester Childrens Hosp, Dept Paediat Nephrol, Manchester, Lancs, England.[Paglialunga, Antonino] ASP Ragusa, Modica, Italy.[Servais, Aude] CHU Necker, APHP, Dept Nephrol, Paris, France.[Lutovac, Branko] Inst Childrens Dis, Clin Ctr Montenegro, Podgorica, Montenegro.[Hoorn, Ewout J.] Erasmus MC, Rotterdam, Netherlands.[Shasha-Lavsky, Hadas] Galilee Med Ctr, Nahariyya, Israel.[Harambat, Jerome; Godron-Dubrasquet, Astrid] Bordeaux Univ Hosp, Pediat Nephrol Unit, Bordeaux, France.[Buder, Kathrin] Univ Hosp Carl Gustav Carus Dresden, Pediat Dept, Dresden, Germany.[Allard, Lise] Angers Univ Hosp, Dept Pediat, Angers, France.[Patzer, Ludwig] Childrens Hosp St Elisabeth & St Barbara, Halle, Germany.[Shumikhina, Marina] Filatov Childrens Clin Hosp 13, Moscow, Russia.[Hansen, Matthias] Clementine Childrens Hosp, KfH Ctr Paediat Nephrol, Frankfurt, Germany.[Printza, Nikoleta] Aristotle Univ Thessaloniki, Pediat Dept 1, Thessaloniki, Greece.[Kucuk, Nuran] Kartal Dr Lutfi Kirdar Training & Res Hosp, Istanbul, Turkey.[Beringer, Ortraud] Univ Childrens Hosp, Ulm, Germany.[Bhimma, Rajendra] Cent Hosp, Inkosi Albert Luthuli, Durban, South Africa.[Cerkauskiene, Rimante] Vilnius Univ, Childrens Hosp, Fac Med, Vilnius, Lithuania.[Cerkauskiene, Rimante] Vilnius Univ Hosp, Santaros Klin, Vilnius, Lithuania.[Neuhaus, Thomas J.] Cantonal Hosp Lucerne, Childrens Hosp Lucerne, Luzern, Switzerland.[Stavileci, Valbona] Pediat Clin, Prishtina, Kosovo.[Ulinski, Tim] Armand Trousseau Univ Hosp, APHP, Pediat Nephrol Dept, Paris, France.[Dincel, Nida Temizkan] Hlth Sci Univ, Izmir Dr Behcet Uz Childrens Hosp, Izmir, Turkey.[Mohebbi, Nilufar] Univ Hosp Zurich, Div Nephrol, Zurich, Switzerland

ADPedKD: A Global Online Platform on the Management of Children With ADPKD

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of renal failure. For several decades, ADPKD was regarded as an adult-onset disease. In the past decade, it has become more widely appreciated that the disease course begins in childhood. However, evidence-based guidelines on how to manage and approach children diagnosed with or at risk of ADPKD are lacking. Also, scoring systems to stratify patients into risk categories have been established only for adults. Overall, there are insufficient data on the clinical course during childhood. We therefore initiated the global ADPedKD project to establish a large international pediatric ADPKD cohort for deep characterization. Methods: Global ADPedKD is an international multicenter observational study focusing on childhood-diagnosed ADPKD. This collaborative project is based on interoperable Web-based databases, comprising 7 regional and independent but uniformly organized chapters, namely Africa, Asia, Australia, Europe, North America, South America, and the United Kingdom. In the database, a detailed basic data questionnaire, including genetics, is used in combination with data entry from follow-up visits, to provide both retrospective and prospective longitudinal data on clinical, radiologic, and laboratory findings, as well as therapeutic interventions. Discussion: The global ADPedKD initiative aims to characterize in detail the most extensive international pediatric ADPKD cohort reported to date, providing evidence for the development of unified diagnostic, follow-up, and treatment recommendations regarding modifiable disease factors. Moreover, this registry will serve as a platform for the development of clinical and/or biochemical markers predicting the risk of early and progressive disease