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Context: The pathophysiology of cystinosis-associated metabolic bone disease is complex., Objective: We hypothesized a disturbed interaction between osteoblasts and osteoclasts., Methods: This binational cross-sectional multicenter study included 103 patients with cystinosis (61% children) with chronic kidney disease (CKD) stages 1 to 5D/T at hospital clinics. Ten key bone markers were evaluated., Results: Skeletal complications occurred in two-thirds of the patients, with adults having a 5-fold increased risk compared with children. Patients with CKD stages 1 to 3 showed reduced z-scores for serum phosphate and calcium and suppressed fibroblast growth factor 23 (FGF23) and parathyroid hormone levels, in conjunction with elevated bone-specific alkaline phosphatase levels. Serum phosphate was associated with estimated glomerular filtration rate, combined phosphate and active vitamin D treatment, and native vitamin D supplementation, while serum calcium was associated with age and dosage of active vitamin D. Sclerostin was generally elevated in children, and associated with age, FGF23 levels, and treatment with active vitamin D and growth hormone. The osteoclast marker tartrate-resistant acid phosphatase 5b was increased, and associated with age and treatment with active vitamin D. The ratio of soluble ligand of receptor activator of nuclear factor-κB (sRANKL) and osteoprotegerin (OPG), a surrogate for the regulation of osteoclastogenesis by osteoblasts, was decreased and associated with phosphate and 1,25(OH)2D3 levels. These changes were only partly corrected after transplantation., Conclusion: Bone health in cystinosis deteriorates with age, which is associated with increased osteoclast activity despite counter-regulation of osteoblasts via OPG/RANKL, which in conjunction with elevated sclerostin levels and persistent rickets/osteomalacia, may promote progressive bone loss., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Background: Therapeutic apheresis (TA) are promising treatment option for neuroimmunological disorders. In paediatrics, the available data is limited, particularly for the use of IA. The aim of this study was to analyse the use of PE and IA in children and adolescents, with emphasis on outcome and neurological course after treatment as well as the safety of the two modalities., Methods: Clinical data from paediatric patients with neuroimmunological disorders treated with TA in two German university children's hospitals between 2015 and 2022 were retrospectively analysed., Results: In total, 39 patients underwent 322 sessions of TA, of which 184 were IA and 138 PE. The most common diagnosis was autoimmune encephalitis in 39 % (n = 15) of the patients. Other indications were central nervous system inflammatory demyelinating disorders in 21 % (n = 8), Guillain-Barré syndrome in 18 % (n = 7), Myelin Oligodendrocyte Glycopeptide-antibody associated syndromes in 8 % (n = 3), Myasthenia gravis in 5 % (n = 2) and other neurological disorders in 10 % (n = 4). Overall, there was an improvement in 76 % of patients (81 % with IA, 70 % with PE; p = 0.41) immediately after treatment and an improvement in 88 % of patients (90 % with IA, 85 % with PE; p = 0.63) one month after treatment. Complications occurred in 13 % of all sessions (13 % with IA and 13 % with PE; p = 1). Most complications were considered as moderate., Conclusion: Both, IA and PE, are effective treatment options in the therapy of neuroimmunological disorders in children and adolescents, with no major differences in terms of efficiency or safety., Competing Interests: Declaration of competing interest None of the authors has any conflicts of interest to declare in association with this manuscript., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We present a case of lamotrigine-triggered DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome with acute kidney injury stage 3. A 17-year-old girl with known epilepsy treated with lamotrigine presented with acute kidney injury as well as skin eruption, fever, and apathy. Extended diagnostics, considering infectious and autoimmune diseases, remained unremarkable. Lamotrigine blood levels were within the target range. Kidney biopsy showed acute interstitial nephritis with tubular necrosis. Methylprednisolone pulse therapy led to an improvement in kidney function; skin eruption and neurological symptoms resolved. During the hospital stay, the girl admitted to inconsistent and variable intake of lamotrigine, occasionally resulting in notable overdosing. This report demonstrates that acute kidney injury in lamotrigine-induced DRESS syndrome is an acute interstitial nephritis with tubular necrosis, an aspect that has not been deeply characterized so far. Additionally, we aim to elevate awareness towards non-adherence as cause of disease, especially among the adolescent population., (© 2024. The Author(s).)

Introduction: The choice and timing of kidney replacement therapy (KRT) is influenced by clinical factors, laboratory features, feasibility issues, family preferences, and clinicians' attitudes. We analyzed the factors associated with KRT modality and timing in a multicenter, multinational prospective pediatric cohort study., Methods: A total of 695 pediatric patients with chronic kidney disease (CKD) enrolled into the Cardiovascular Comorbidity in Children with CKD (4C) study at age 6 to 17 years with estimated glomerular filtration rate (eGFR) of 10 to 60 ml/min per 1.73 m 2 were investigated. Competing risk regression was performed to identify factors associated with initiation of dialysis or preemptive transplantation (Tx), including primary renal diagnosis, demographics, anthropometrics, and laboratory parameters., Results: During the 8-year observation period, 342 patients (49%) started KRT. Of these, 200 patients started dialysis, whereas 142 patients underwent preemptive Tx. A lower eGFR at enrolment (Hazard ratio [HR]: 0.76 [95% confidence interval: 0.74-0.78]), a steeper eGFR slope (HR: 0.90 [0.85-0.95], and a higher systolic blood pressure SD score (SDS) (HR: 2.07 [1.49-2.87]) increased the likelihood of KRT initiation. Patients with glomerulopathies were more likely to start dialysis than children with congenital anomalies of the kidneys and urinary tracts (CAKUT) (HR: 3.81 [2.52-5.76]). Lower body mass index (BMI) SDS (HR: 0.73 [0.6-0.89]) and lower hemoglobin (HR: 0.8 [0.72-0.9]) were associated with higher likelihood of dialysis. A significant center effect was observed, accounting for 6.8% (dialysis) to 8.7% (preemptive Tx) of explained variation., Conclusion: The timing and choice of KRT in pediatric patients is influenced by the rate of kidney function loss, the underlying kidney disease, nutritional status, blood pressure, anemia and center-specific factors., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Introduction: Hepatocyte nuclear factor 1-beta ( HNF1B ) gene variants or the chromosome 17q12 deletion (17q12del) represent the most common monogenic cause of developmental kidney disease. Although neurodevelopmental disorders have been associated with the 17q12del, specific genotype-phenotype associations with respect to kidney function evolution have not yet been fully defined. Here, we aimed to determine whether 17q12del or specific HNF1B variants were associated with kidney survival in a large patient population with HNF1B disease., Methods: This was a retrospective observational study involving 521 patients with HNF1B disease from 14 countries using the European Reference Network for rare kidney diseases with detailed information on the HNF1B genotype ( HNF1B variants or the 17q12del). Median follow-up time was 11 years with 6 visits per patient. The primary end point was progression to chronic kidney disease (CKD) stage 3 (estimated glomerular filtration rate [eGFR] < 60 ml/min per 1.73 m 2 ). Secondary end points were the development of hypomagnesemia or extrarenal disorders, including hyperuricemia and hyperglycemia., Results: Progression toward CKD stage 3 was significantly delayed in patients with the 17q12del compared to patients with HNF1B variants (hazard ratio [HR]: 0.29, 95% confidence interval [CI]: 0.19-0.44, P  < 0.001). Progression toward CKD stage 3 was also significantly delayed when HNF1B variants involved the HNF1B Pit-1, Oct-1, and Unc-86 homeodomain (POU h ) DNA-binding and transactivation domains rather than the POU-specific domain (POU s ) DNA-binding domain (HR: 0.15 [95% CI: 0.06-0.37), P  < 0.001 and HR: 0.25 (95% CI: 0.11-0.57), P  = 0.001, respectively). Finally, the 17q12del was positively associated with hypomagnesemia and negatively associated with hyperuricemia, but not with hyperglycemia., Conclusion: Patients with the 17q12del display a significantly better kidney survival than patients with other HNF1B variants; and for the latter, variants in the POU s DNA-binding domain lead to the poorest kidney survival. These are clinically relevant HNF1B kidney genotype-phenotype correlations that inform genetic counseling., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Introduction: Fluid and salt overload in patients on dialysis result in high blood pressure (BP), left ventricular hypertrophy (LVH) and hemodynamic instability, resulting in cardiovascular morbidity., Methods: Analysis of 910 pediatric patients on maintenance hemodialysis/hemodiafiltration (HD/HDF), prospectively followed-up with 2758 observations recorded every 6-months in the International Pediatric Hemodialysis Network (IPHN)., Results: Uncontrolled hypertension was present in 55% of observations, with 27% of patients exhibiting persistently elevated predialysis BP. Systolic and diastolic age- and height-standardized BP (BP-SDS) were independently associated with the number of antihypertensive medications (odds ratio [OR] = 1.47, 95% confidence interval 1.39-1.56, 1.36 [1.23-1.36]) and interdialytic weight gain (IDWG; 1.19 [1.14-1.22], 1.09 [1.06-1.11]; all  P  < 0.0001). IDWG was related to urine output (OR = 0.27 [0.23-0.32]) and dialysate sodium (dNa; 1.06 [1.01-1.10]; all P  < 0.0001). The prevalence of masked hypertension was 24%, and HD versus HDF use was an independent risk factor of elevated age- and height-standardized mean arterial pressure (MAP-SDS) (OR = 2.28 [1.18-4.41], P  = 0.01). Of the 1135 echocardiograms, 51% demonstrated LVH. Modifiable risk factors included predialysis systolic BP-SDS (OR = 1.06 [1.04-1.09], P  < 0.0001), blood hemoglobin (0.97 [0.95-0.99], P = 0.004), HD versus HDF modality (1.09 [1.02-1.18], P  = 0.01), and IDWG (1.02 [1.02-1.03], P  = 0.04). In addition, HD modality increased the risk of LVH progression (OR = 1.23 [1.03-1.48], P = 0.02). Intradialytic hypotension (IDH) was prevalent in patients progressing to LVH and independently associated with predialysis BP-SDS below 25th percentile, lower number of antihypertensives, HD versus HDF modality, ultrafiltration (UF) rate, and urine output, but not with dNa., Conclusion: Uncontrolled hypertension and LVH are common in pediatric HD, despite intense pharmacologic therapy. The outcome may improve with use of HDF, and superior anemia and IDWG control; the latter via lowering dNa, without increasing the risk of IDH., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Background: Infantile nephropathic cystinosis (INC) is a systemic lysosomal storage disease causing intracellular cystine accumulation, resulting in renal Fanconi syndrome, progressive kidney disease (CKD), rickets, malnutrition, and myopathy. An INC-specific disproportionately diminished trunk length compared to leg length poses questions regarding the functionality of the trunk., Methods: Thus, we prospectively investigated thoracic dimensions and proportions, as well as their clinical determinants in 44 pediatric patients with INC with CKD stages 1-5 and 97 age-matched patients with CKD of other etiology between the ages of 2-17 years. A total of 92 and 221 annual measurements of patients with INC and CKD, respectively, were performed, and associations between anthropometric and clinical parameters were assessed using linear mixed-effects models., Results: Patients with INC exhibited altered chest dimensions that were distinct from CKD controls, characterized by markedly increased chest depth to height and chest depth to chest width ratio z-scores (> 1.0), while those of patients with CKD were only mildly affected (z-score within ± 1.0). Ratio z-scores differed significantly between both patient groups from 2-6 years of age onward. The degree of chest disproportion in INC patients was significantly associated with both the degree of CKD and tubular dysfunction (e.g., low serum phosphate and bicarbonate) across three different age groups (2-6, 7-12, and 13-17 years)., Conclusion: Our data show an INC-specific alteration in thoracic shape from early childhood onward, which is distinct from CKD of other etiologies, suggesting early childhood subclinical changes of the musculoskeletal unit of the thoracic cage, which are associated with kidney function. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2023. The Author(s).)

Neonatal sclerosing cholangitis (NSC) is associated with progressing biliary fibrosis that often requires liver transplantation in childhood. Several recent studies have identified variants in DCDC2, encoding doublecortin domain-containing protein 2 (DCDC2), expressed in primary cilia, that accompany syndromic disease and NSC. We report four patients with hepatobiliary disease associated with two novel homozygous or compound heterozygous variants in DCDC2. Three patients with protein-truncating variants in DCDC2, expressing no DCDC2, presented with the originally described severe hepatic phenotype in infancy. One patient with a novel homozygous DCDC2 missense variant shows a markedly milder phenotype only manifest in childhood and with retained DCDC2 expression. Concomitant nephronophthisis is present in three patients and learning disability in two. This report widens the phenotypic spectrum of DCDC2-associated hepatobiliary disease. Testing for DCDC2 expression and DCDC2 variants should be included in the evaluation of cholangiopathy of unknown aetiology in childhood as well as in infancy., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Chronic life-limiting illnesses such as chronic kidney disease (CKD) require integral support to the families concerned in addition to medical care. Palliative care is an option to facilitate families to address future concerns, such as procedures for acute life-threatening complications, or to relieve physical and psychosocial suffering. The exact needs of patients or parents have not yet been investigated. To assess needs in supportive palliative care, we conducted a monocentric qualitative interview study. We included patients 14 to 24 years old as well as parents of younger children (below 14 years) with CKD ≥ stage 3. In total, fifteen interviews were conducted. Data were analyzed with a deductive and descriptive approach using qualitative content analysis as described by Mayring. Sociodemographic data and basic information of disease were collected using questionnaires. In contrast to caregivers, adolescents and young adults do not express worries about their own mortality or reduced life expectancy. Rather, they report about their limitations to everyday life associated with the disease, especially in the areas of school and work. They wish to live a normal life. Caregivers are concerned about the future and the disease trajectory. They also describe difficulties in balancing the management of the disease with other responsibilities such as work and healthy siblings' needs. Patients and caregivers appear to need a chance to talk about their everyday struggles and disease-related fears and concerns. Talking about their concerns and needs may help deal with their emotions and facilitate acceptance of their situation characterized by a life-limiting disease. Our study confirms the need for psychosocial support in pediatric nephrology to address the needs of the affected families. This can be offered by pediatric palliative care teams.

Protection of adult kidney transplant recipients against SARS-CoV2 was shown to be strongly impaired owing to low reactogenicity of available vaccines. So far, data on vaccination outcomes in adolescents are scarce due to later vaccination approval for this age group. We therefore comprehensively analyzed vaccination-specific humoral-, T- and B-cell responses in kidney transplanted adolescents aged 12-18 years in comparison to healthy controls 6 weeks after standard two-dose BNT162b2 ("Comirnaty"; Pfizer/BioNTech) vaccination. Importantly, 90% (18/20) of transplanted adolescents showed IgG seroconversion with 75% (15/20) developing neutralizing titers. Still, both features were significantly diminished in magnitude compared to controls. Correspondingly, spike-specific B cells were quantitatively reduced and enriched for non-isotype-class-switched IgD + 27 + memory cells in patients. Whereas spike specific CD4 + T cell frequencies were similar in both groups, cytokine production and memory differentiation were significantly impaired in transplant recipients. Although our data identify limitations in all arms of vaccine-specific immunity, the majority of our adolescent patients showed robust humoral responses despite antimetabolite-based treatment being associated with poor vaccination outcomes in adults., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sattler, Thumfart, Tóth, Schrezenmeier, Proß, Stahl, Siegle, He, Thole, Ludwig, Straub-Hohenbleicher, Friedersdorff, Jahrsdörfer, Schrezenmeier, Bufler and Kotsch.)

Introduction: Nephronophthisis (NPH) comprises a group of rare disorders accounting for up to 10% of end-stage kidney disease (ESKD) in children. Prediction of kidney prognosis poses a major challenge. We assessed differences in kidney survival, impact of variant type, and the association of clinical characteristics with declining kidney function., Methods: Data was obtained from 3 independent sources, namely the network for early onset cystic kidney diseases clinical registry ( n = 105), an online survey sent out to the European Reference Network for Rare Kidney Diseases ( n = 60), and a literature search ( n = 218)., Results: A total of 383 individuals were available for analysis: 116 NPHP1 , 101 NPHP3 , 81 NPHP4 and 85 NPHP11/TMEM67 patients. Kidney survival differed between the 4 cohorts with a highly variable median age at onset of ESKD as follows: NPHP3, 4.0 years (interquartile range 0.3-12.0); NPHP1 , 13.5 years (interquartile range 10.5-16.5); NPHP4, 16.0 years (interquartile range 11.0-25.0); and NPHP11/TMEM67, 19.0 years (interquartile range 8.7-28.0). Kidney survival was significantly associated with the underlying variant type for NPHP1 , NPHP3 , and NPHP4 . Multivariate analysis for the NPHP1 cohort revealed growth retardation (hazard ratio 3.5) and angiotensin-converting enzyme inhibitor (ACEI) treatment (hazard ratio 2.8) as 2 independent factors associated with an earlier onset of ESKD, whereas arterial hypertension was linked to an accelerated glomerular filtration rate (GFR) decline., Conclusion: The presented data will enable clinicians to better estimate kidney prognosis of distinct patients with NPH and thereby allow personalized counseling., (© 2022 International Society of Nephrology. Published by Elsevier Inc.)

Introduction: Autosomal recessive polycystic kidney disease (ARPKD) is a rare monogenic disorder characterized by early onset fibrocystic hepatorenal changes. Previous reports have documented pronounced phenotypic variability even among siblings in terms of patient survival. The underlying causes for this clinical variability are incompletely understood., Methods: We present the longitudinal clinical courses of 35 sibling pairs included in the ARPKD registry study ARegPKD, encompassing data on primary manifestation, prenatal and perinatal findings, genetic testing, and family history, including kidney function, liver involvement, and radiological findings., Results: We identified 70 siblings from 35 families with a median age of 0.7 (interquartile range 0.1-6.0) years at initial diagnosis and a median follow-up time of 3.5 (0.2-6.2) years. Data on PKHD1 variants were available for 37 patients from 21 families. There were 8 patients from 7 families who required kidney replacement therapy (KRT) during follow-up. For 44 patients from 26 families, antihypertensive therapy was documented. Furthermore, 37 patients from 24 families had signs of portal hypertension with 9 patients from 6 families having substantial hepatic complications. Interestingly, pronounced variability in the clinical course of functional kidney disease was documented in only 3 sibling pairs. In 17 of 20 families of our cohort of neonatal survivors, siblings had only minor differences of kidney function at a comparable age., Conclusion: In patients surviving the neonatal period, our longitudinal follow-up of 70 ARPKD siblings from 35 families revealed comparable clinical courses of kidney and liver diseases in most families. The data suggest a strong impact of the underlying genotype., (© 2022 International Society of Nephrology. Published by Elsevier Inc.)

Objective: To introduce and evaluate a modified version of the "zipper method"-a treatment strategy alternating intravenous immunoglobulin (IVIG) and plasma exchange (PLEX) first reported for 9 pediatric cases of Guillain-Barré syndrome in 2018-for treatment of severe immune-mediated neurologic disorders in children., Methods: The modified zipper method comprised longer intervals between PLEX-IVIG cycles (48   hours instead of 24   hours), more cycles (7-10 instead of 5), a consistent plasma volume exchange (instead of the original multistep approach), and variable infusion times for IVIGs (4-8   hours). The modified zipper method was applied as an individual treatment approach once standard therapy failed. The follow-up ranged from 6 months to 2 years. Cases were analyzed retrospectively. Disease severity was mainly quantified by the Guillain-Barré syndrome disability score., Results: Four children (9-15 years) with (1) Miller-Fisher syndrome, (2) Bickerstaff brainstem encephalitis, (3) common Guillain-Barré syndrome, and (4) severe acute disseminated encephalomyelitis were treated by the modified zipper method. Results for duration of mechanical ventilation (median of 12 days, interquartile range [IQR] 8-16), hospital stay (median of 23 days, IQR 22-24), and time to unaided walking (median of 22 days, IQR 21-37) outperformed previous studies with IVIG/PLEX alone or IVIG + PLEX combinations unlike the zipper method., Conclusion: The modified zipper method is associated with a low mortality, a short mechanical ventilation time, a short hospital stay, and an excellent outcome in children with severe Guillain-Barré syndrome or acute disseminated encephalomyelitis. Our regimen is streamlined for applicability. Results emphasize its robust effectiveness as an option for therapy escalation in severe neuroimmunologic diseases. Now, multicenter trials are needed to evaluate this novel treatment strategy.

Background: To describe treatment practices for juvenile proliferative lupus nephritis (LN) class III and IV of pediatric rheumatologists and nephrologists in Germany and Austria in preparation for a treat-to-target treatment protocol in LN., Methods: Survey study by members of the Society for Pediatric and Adolescent Rheumatology (GKJR) and the German Society for Pediatric Nephrology (GPN) on diagnostics and (concomitant) therapy of LN., Results: Fifty-eight physicians completed the survey. Overall, there was a considerable heterogeneity regarding the suggested diagnostics and management of juvenile proliferative LN. Increased urinary protein excretion, either assessed by 24 h urine collection or spot urine (protein-creatinine ratio), and reduced estimated glomerular filtration rate were specified as important parameters for indication of kidney biopsy to diagnose proliferative LN and monitoring of therapy. Corticosteroids were generally proposed for induction and maintenance therapy, most often in conjunction with either mycophenolate mofetil (MMF) or cyclophosphamide (CP) as steroid-sparing immunosuppressants. MMF was clearly preferred over CP for induction therapy of LN class III, whereas CP and MMF were equally proposed for LN class IV. MMF was most often recommended for maintenance therapy in conjunction with oral corticosteroids and continued for at least 3 years and 1 year, respectively, after remission. Hydroxychloroquine was widely accepted as a concomitant measure followed by renin-angiotensin system inhibitors in cases of arterial hypertension and/or proteinuria., Conclusion: The majority of pediatric rheumatologists and nephrologists in Germany and Austria propose the use of corticosteroids, most often in combination with either MMF or CP, for treatment of proliferative LN in children. The considerable heterogeneity of responses supports the need for a treat-to-target protocol for juvenile proliferative LN between pediatric rheumatologists and nephrologists., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Vollbach, Schuetz, Hedrich, Speth, Mönkemöller, Brunner, Neudorf, Rietschel, Hospach, Kallinich, Hinze, Wagner, Tönshoff, Weber, Latta, Thumfart, Bald, Wiemann, Zappel, Tenbrock and Haffner.)

Background: Therapeutic apheresis (TA) is based on the principles of either removing dissolved pathogenic substances (e.g., antibodies) from the blood plasma or replacing plasma factors. It expands the therapeutic scope for a variety of diseases. Safety analysis in the pediatric field are scant. The aim of this analysis was to analyze specific complications of TA modalities - plasma exchange (PE) and immunoadsorption (IA) - in children and adolescents., Methods: Children and adolescents ( n = 298) who had received TA from 2008 to 2018 in five pediatric nephrology centers were analyzed retrospectively. In total, 4.004 treatments (2.287 PE and 1.717 IA) were evaluated., Results: Indications for TA were mainly nephrological and neurological diseases. The three main indications were antibody-mediated graft rejection (13.4%), hemolytic uremic syndrome mainly with neurological involvement (12.8%), and AB0-incompatible transplantation (11.7%). Complications developed in 440 of the 4004 sessions (11%), of which one third were non-specific (nausea, headache). IA was better tolerated than PE. Complications were reported in 9.5% ( n = 163) of the IA versus 12.1% (277) of the PE sessions ( p < 0.001). When considering different types of complications, significantly more non-specific/non-allergic events ( p = 0.02) and allergic reactions occurred in PE sessions ( p < 0.001). More complications occurred with PE, when using fresh frozen plasma (16.2%; n = 145) in comparison to human albumin (14.5%; n = 115) ( p < 0.001)., Conclusions: Therapeutic apheresis in childhood and adolescence is a safe treatment procedure. IA showed a lower complication rate than PE. Therefore, IA may be preferably provided if the underlying disease pathomechanisms do not require PE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Taylan, Schaaf, Dorn, Schmitt, Loos, Kanzelmeyer, Pape, Müller, Weber and Thumfart.)

Children with infantile nephropathic cystinosis (INC), an inherited lysosomal storage disease resulting in cystine accumulation in all body cells, are prone to progressive chronic kidney disease (CKD), impaired growth and reduced weight gain; however, systematic anthropometric analyses are lacking. In this prospective multicenter study we investigated linear growth, body proportion, body mass index (BMI), upper arm fat area (UFA) and biochemical parameters in 43 pediatric INC patients with CKD stages 1 to 5 and 49 age-matched CKD controls, with 193 annual measurements. INC patients showed more impaired height than CKD controls (-1.8 vs -0.7 z-score; P < .001), despite adequate cysteamine therapy, treatment for Fanconi syndrome and more frequent use of growth hormone. Only the youngest INC patients shared the same body pattern with CKD controls characterized by preferential impairment of leg length and rather preserved trunk length. In late-prepuberty, body pattern changed only in INC patients due to improved leg growth and more impaired trunk length. Mean UFA z-score in INC patients was slightly reduced in early childhood and progressively decreased thereafter reaching -0.8 z-score in adolescence, while CKD controls showed a steady increase in standardized BMI and UFA especially during adolescent age. Menarche in female INC patients was significantly delayed compared to CKD controls. Our data indicate that with age and progression of disease, pediatric INC patients undergo unique changes of body growth and fat stores that are distinct from those with CKD stemming from other causes, suggesting other factors apart from CKD to contribute to this development. Pediatric patients with infantile nephropathic cystinosis display more severe impaired linear growth than other peer CKD patients, despite of cysteamine treatment, supplementation for Fanconi syndrome, and more frequent use of growth hormone, with a distinct change of body proportions and overall lower body fat., (© 2022 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

Autosomal recessive polycystic kidney disease (ARPKD) is a severe disease of early childhood that is clinically characterized by fibrocystic changes of the kidneys and the liver. The main cause of ARPKD are variants in the PKHD1 gene encoding the large transmembrane protein fibrocystin. The mechanisms underlying the observed clinical heterogeneity in ARPKD remain incompletely understood, partly due to the fact that genotype-phenotype correlations have been limited to the association of biallelic null variants in PKHD1 with the most severe phenotypes. In this observational study we analyzed a deep clinical dataset of 304 patients with ARPKD from two independent cohorts and identified novel genotype-phenotype correlations during childhood and adolescence. Biallelic null variants frequently show severe courses. Additionally, our data suggest that the affected region in PKHD1 is important in determining the phenotype. Patients with two missense variants affecting amino acids 709-1837 of fibrocystin or a missense variant in this region and a null variant less frequently developed chronic kidney failure, and patients with missense variants affecting amino acids 1838-2624 showed better hepatic outcome. Variants affecting amino acids 2625-4074 of fibrocystin were associated with poorer hepatic outcome. Thus, our data expand the understanding of genotype-phenotype correlations in pediatric ARPKD patients and can lay the foundation for more precise and personalized counselling and treatment approaches., (Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Hemolytic uremic syndrome caused by invasive pneumococcal disease (P-HUS) is rare in children and adolescents, but accompanied by high mortality in the acute phase and complicated by long-term renal sequelae. Abnormalities in the alternative complement pathway may additionally be contributing to the course of the disease but also to putative treatment options., Methods: Retrospective study to assess clinical course and laboratory data of the acute phase and outcome of children with P-HUS., Results: We report on seven children (median age 12 months, range 3-28 months) diagnosed with P-HUS. Primary organ manifestation was meningitis in four and pneumonia in three patients. All patients required dialysis which could be discontinued in five of them after a median of 25 days. In two patients, broad functional and genetic complement analysis was performed and revealed alternative pathway activation and risk haplotypes in both. Three patients were treated with the complement C5 inhibitor eculizumab. During a median follow-up time of 11.3 years, one patient died due to infectious complications after transplantation. Two patients showed no signs of renal sequelae., Conclusions: Although pathophysiology in P-HUS remains as yet incompletely understood, disordered complement regulation seems to provide a clue to additional insights for pathology, diagnosis, and even targeted treatment.

Background: To analyse the validity of membrane-bound SIGLEC1 (CD169) as a sensitive biomarker for monitoring disease activity in pediatric systemic lupus erythematosus (SLE)., Methods: 27 children and adolescents with SLE were followed for a mean of 13.5 months. During consecutive routine visits SLEDAI-2k, C3, C4 and ds-DNA values were determined. Additionally, expression of SIGLEC1 on monocytes was determined by flow cytometry. The amount of PE-labelled CD169 mAb bound per monocyte was analyzed using QuantiBRITE™ PE tubes. Associations between biomarkers and the clinical course were investigated by regression analysis., Results: In general, SIGLEC1 expression is high on SLE-derived monocytes (mean 6 359 (SD 6 056) molecules/monocyte, cut-off 2 500 molecules/monocyte), all patients with newly diagnosed SLE exhibit elevated expression (mean 13366 (SD 7 750) molecules/monocyte). Changes (Δ) in SIGLEC1 levels during the clinical course is the only biomarker that significantly correlates with the change in SLEDAI-2k (beta ST  = 0.28, p = 0.001). At follow-up visit, a clinically important worsening was experienced by 47.6% of patients with a Δ SIGLEC1 > 2 151 molecules/cell (OR 5.31) and 72.4% with a Δ SIGLEC1 > 756 molecules/cell (OR 8.90). Conversely, 36.4% of patients with a Δ SIGLEC1 < -2 818 molecules/cell (OR 4.16, percentiles as cut-off criteria) and 50.0% of patients with a Δ SIGLEC1 < -1 370 molecules/cell (OR 3.55, application of Youden index) showed clinical improvement. SIGLEC1 expression correlates inversely with the amount of therapeutically applied hydroxychloroquine (p < 0.001)., Conclusions: SIGLEC1 expression on monocytes is a sensitive biomarker for adjusting disease activity in childhood SLE and represents a promising and easily applicable tool for disease monitoring.

Context: Children with nephropathic cystinosis (NC) show persistent hypophosphatemia, due to Fanconi syndrome, as well as mineral and bone disorders related to chronic kidney disease (CKD); however, systematic analyses are lacking., Objective: To compare biochemical parameters of bone and mineral metabolism between children with NC and controls across all stages of CKD., Design: Cross-sectional multicenter study., Setting: Hospital clinics., Patients: Forty-nine children with NC, 80 CKD controls of the same age and CKD stage., Main Outcome Measures: Fibroblast growth factor 23 (FGF23), soluble Klotho, bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin, osteoprotegerin (OPG), biochemical parameters related to mineral metabolism, and skeletal comorbidity., Results: Despite Fanconi syndrome medication, NC patients showed an 11-fold increased risk of short stature, bone deformities, and/or requirement for skeletal surgery compared with CKD controls. This was associated with a higher frequency of risk factors such as hypophosphatemia, hypocalcemia, low parathyroid hormone (PTH), metabolic acidosis, and a specific CKD stage-dependent pattern of bone marker alterations. Pretransplant NC patients in mild to moderate CKD showed a delayed increase or lacked an increase in FGF23 and sclerostin, and increased BAP, TRAP5b, and OPG concentrations compared with CKD controls. Post-transplant, BAP and OPG returned to normal, TRAP5b further increased, whereas FGF23 and PTH were less elevated compared with CKD controls and associated with higher serum phosphate., Conclusions: Patients with NC show more severe skeletal comorbidity associated with distinct CKD stage-dependent alterations of bone metabolism than CKD controls, suggesting impaired mineralization and increased bone resorption, which is only partially normalized after renal transplantation., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of end-stage renal disease in children and adolescents. The diversity of the malformations summarized by CAKUT is high and there are numerous associated syndromes. The genetic background of these malformations remains unknown in the majority of cases. The aim of this study was to evaluate factors associated with the development of chronic kidney disease (CKD) and underlying genetic aberrations in children and adolescents with CAKUT. For this purpose, data from patients with CAKUT presented at the pediatric nephrology outpatient clinic were analyzed in a cross-sectional single-center study. Among the 405 patients, the commonest findings related to CAKUT were renal hypoplasia/dysplasia (65%), followed by hydronephrosis (43%). Forty-four percent of the patients were suffering from CKD, 6% were ranked as end-stage renal disease. In the univariate analysis, male gender and premature birth were associated with higher CKD stages ( p = 0.004 resp. p < 0.001). Children with an abnormal prenatal ultrasound had more often a glomerular filtration rate of <30 ml/min/1.73 m 2 ( p = 0.004). Patients with urinary tract infections as first symptom whereas had significant lower CKD stages ( p = 0,006). In the multivariate analysis, premature birth ( p = 0.033) and urinary tract infection as the first symptom ( p = 0.043) were significantly associated with CKD stage ≥ II. Among the 16% of the children who have undergone genetic analyses the most frequent genetic aberration was a mutation in HNF1 β-gene. These results can be used for the care of patients with CAKUT subject to factors associated with developing CKD., (Copyright © 2020 Isert, Müller and Thumfart.)

Rationale & Objective: Arteriovenous fistulas (AVFs) have been recommended as the preferred vascular access for pediatric patients on maintenance hemodialysis (HD), but data comparing AVFs with other access types are scant. We studied vascular access choice, placement, complications, and outcomes in children., Study Design: Prospective observational cohort study., Setting & Participants: 552 children and adolescents from 27 countries on maintenance HD followed up prospectively by the International Pediatric HD Network (IPHN) Registry between 2012 and 2017., Predictor: Type of vascular access: AVF, central venous catheter (CVC), or arteriovenous graft., Outcome: Infectious and noninfectious vascular access complication rates, dialysis performance, biochemical and hematologic parameters, and clinical outcomes., Analytical Approach: Univariate and multivariable linear mixed models, generalized linear mixed models, and proportional hazards models; cumulative incidence functions., Results: During 314 cumulative patient-years, 628 CVCs, 225 AVFs, and 17 arteriovenous grafts were placed. One-third of the children with an AVF required a temporary CVC until fistula maturation. Vascular access choice was associated with age and expectations for early transplantation. There was a 3-fold higher living related transplantation rate and lower median time to transplantation of 14 (IQR, 6-23) versus 20 (IQR, 14-36) months with CVCs compared with AVFs. Higher blood flow rates and Kt/V urea were achieved with AVFs than with CVCs. Infectious complications were reported only with CVCs (1.3/1,000 catheter-days) and required vascular access replacement in 47%. CVC dysfunction rates were 2.5/1,000 catheter-days compared to 1.2/1,000 fistula-days. CVCs required 82% more revisions and almost 3-fold more vascular access replacements to a different site than AVFs (P<0.001)., Limitations: Clinical rather than population-based data., Conclusions: CVCs are the predominant vascular access choice in children receiving HD within the IPHN. Age-related anatomical limitations and expected early living related transplantation were associated with CVC use. CVCs were associated with poorer dialysis efficacy, higher complication rates, and more frequent need for vascular access replacement. Such findings call for a re-evaluation of pediatric CVC use and practices., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Aim: Children and adolescents with end-stage renal disease face a high morbidity and mortality. Palliative care provides a multidisciplinary approach to reduce disease burden and improve quality of life. This study evaluated concepts and current structures of palliative care from the perspective of a multidisciplinary paediatric nephrology team including physicians, nurses and psychosocial health professionals., Methods: Evaluation was done by an online survey sent to the members of the German Society of Nephrology and to the nurse managers of German paediatric dialysis centres between April 9, 2018 and May 31, 2018., Results: Out of the 52 respondents, 54% were physicians, 21% nurses and 25% psychosocial health professionals. The quality of actual palliative care service was rated as moderate (3.3 on a scale from one to six). Specialised palliative care teams (54%) and the caring paediatric nephrologist (50%) were considered as primarily responsible for palliative care. Two thirds wished for training in palliative care. In only 15% of the respondents' centres, palliative care specialisation existed., Conclusion: Palliative care structures in paediatric nephrology were not sufficient in the view of the multidisciplinary healthcare team. Therefore, efforts should be taken to integrate palliative care into the routine treatment of children and adolescents with chronic kidney diseases., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: HNF1B gene mutations are an important cause of bilateral (cystic) dysplasia in children, complicated by chronic renal insufficiency. The clinical variability, the absence of genotype-phenotype correlations, and limited long-term data render counseling of affected families difficult., Methods: Longitudinal data of 62 children probands with genetically proven HNF1B nephropathy was obtained in a multicenter approach. Genetic family cascade screening was performed in 30/62 cases., Results: Eighty-seven percent of patients had bilateral dysplasia, 74% visible bilateral, and 16% unilateral renal cysts at the end of observation. Cyst development was non-progressive in 72% with a mean glomerular filtration rate (GFR) loss of - 0.33 ml/min/1.73m 2 per year (± 8.9). In patients with an increase in cyst number, the annual GFR reduction was - 2.8 ml/min/1.73m 2 (± 13.2), in the total cohort - 1.0 ml/min/1.73m 2 (±10.3). A subset of HNF1B patients differs from this group and develops end stage renal disease (ESRD) at very early ages < 2 years. Hyperuricemia (37%) was a frequent finding at young age (median 1 year), whereas hypomagnesemia (24%), elevated liver enzymes (21%), and hyperglycemia (8%) showed an increased incidence in the teenaged child. Genetic analysis revealed no genotype-phenotype correlations but a significant parent-of-origin effect with a preponderance of 81% of maternal inheritance in dominant cases., Conclusions: In most children, HNF1B nephropathy has a non-progressive course of cyst development and a slow-progressive course of kidney function. A subgroup of patients developed ESRD at very young age < 2 years requiring special medical attention. The parent-of-origin effect suggests an influence of epigenetic modifiers in HNF1B disease.

Background: In Germany, practice patterns of conservative renal care (CRC), dialysis withdrawal (DW), and concomitant palliative care in patients who choose these options are unknown., Method: A survey was designed including 13 structured and one open questions on the management and frequency of CRC and DW, local palliative care structure, and fundamentals of the decision-making process, and addressed to the head physicians of all renal centers (n = 193) of a non-profit renal care provider (KfH - Kuratorium für Dialyse und Nierentransplantation, Neu-Isenburg, Germany)., Results: Response rate was 62.2% (n = 122 centers) comprising 14,197 prevalent dialysis patients and 159,652 renal outpatients. Two-thirds of the respondents were men (85% in the age group between 45 and 64 years). Mean time of experience in renal medicine was 22.2 years in men, 20.8 years in women. 94% of all centers provided CRC with a different frequency and proportion of patients (mean 8.4% of the center population, median 5%, range 0-50%). Mean proportion of DW was 2.85% per year (median 2%, range 1-15%). Physicians and center features were not significantly associated with utilization of CRC or DW. Palliative care management varied including local palliative teams, support by general physicians, or by the renal team itself. Hospice care was only established in patients undergoing CRC. Fundamentals of the decision-making process were the desire of the patient (90% in CRC, 67% in DW). Patients undergoing CRC changed their opinion towards treatment modality "frequently" in 18% of the cases, "occasionally" in 73%. Physicians' decisions were mostly driven by presumed fatal prognosis and poor physical or mental conditions of the individual patient. Different barriers to provide palliative care for the renal population like lack of education in palliative medicine, shortness of staff, lack of financial resources, and local palliative care structures were reported., Conclusion: Compared to international numbers, in Germany, proportion of CRC and DW reported by non-profit renal centers is in the lower range. Center practice of palliative care management varies and is driven by availability of local palliative care resources and presumably by attitudes of the renal teams. Quality of palliative care and the decision-making process need further evaluation., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Background: Membranoproliferative glomerulonephritis (MPGN) is a rare cause of glomerulopathy in children. Recently, a new classification based on immunohistological features has been established. Infections and anomalies in complement-regulating genes, leading to alternative complement pathway activation, are suspected to trigger the disease. Nevertheless, little is known about optimal treatment and outcome in children with immune-complex-MPGN (IC-MPGN) and C3-glomerulopathy (C3G)., Methods: The method used is retrospective analysis of clinical, histological, and genetic characteristics of 14 pediatric patients with MPGN in two medical centers., Results: Mean age of the patients was 10.6 ± 4.5 years. Patients were grouped into C3G (n = 6) and IC-MPGN (n = 8). One patient showed a likely pathogenic variant in the CFHR5 gene. All 10 patients had risk polymorphisms in complement-regulating genes. Most patients were treated with ACE inhibition, steroids, and mycophenolate mofetil. Three patients with C3G received eculizumab. Median follow-up was 2.3 years. After 1 year of disease, three patients (two C3G, one IC-MPGN) reached complete, five patients partial (three IC-MPGN, two C3G), and five patients no remission (four IC-MPGN, one C3G). One patient progressed to end-stage renal disease (ESRD) 6 years after disease onset., Conclusions: IC-MPGN and C3G are rare disorders in children. Most patients have signs of complement activation associated with risk polymorphisms or likely pathogenic variants in complement-regulating genes. Steroids and mycophenolate mofetil seem to be effective and for some patients, eculizumab might be a treatment option. Outcome is heterogeneous and precise differentiation between IC-MPGN and C3G is still pending.

Aims: Intensified hemodialysis (HD) programs have been developed to overcome the shortcomings of conventional HD. However, there are no data on the implementation of intensified HD programs into routine care. Therefore, we investigated the attitude of nephrologists towards intensified HD, its penetrance into clinical practice, and barriers to implementation., Materials and Methods: We performed an online survey within the German Society of Nephrology on the beliefs and attitudes towards intensified HD., Results: 44% of the respondents believe that there is sufficient evidence in favor of intensified HD independent of whether the respondent offers intensified HD or not. Before expanding intensified HD, adequate funding (81%) and more staff (60%) are needed. 44% of the respondents offer intensified HD to their patients. The offer of intensified HD is made to the patients mainly if the patient is not adequately treated with conventional HD (50%); only 19% offer it routinely to all patients with CKD stage 4, in preparation for renal replacement therapy. 33% of the respondents offer short daily HD, 70% nocturnal intermittent, and 4% daily nocturnal. In 30% of the respondent centers, intensified dialysis is performed at home., Conclusion: Nearly one-half of the respondents already offer intensified HD. Inappropriate funding of intensified HD programs represents the most important barrier for further implementation.
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Introduction: Hemolytic-uremic syndrome (HUS) is a common cause for intrarenal acute kidney injury in childhood. More than 90% of HUS cases are associated with an infection by Shigatoxin-producing Escherichia coli (STEC) whereas the reminder comprises a heterogeneous group (here classified as Non-STEC-HUS). Renal impairment can persist in patients with HUS. This study presents data from four decades investigating the short- and long-term outcome of HUS in childhood. Materials and Methods: In a retrospective single-center-study clinical and laboratory data of the acute phase and of 1- to 10-year follow-up visits of children with HUS were analyzed. Results: 92 HUS-patients were identified from 1996 to 2014 (STEC-HUS-group: n = 76; Non-STEC-HUS-group: n = 16) and 220 HUS-patients between 1976 and 1995. STEC-HUS was increasingly caused by Non-O157 strains and mortality rate declined over the past decades (1.3 vs. 9.5%). Renal sequelae persisted more often in the group 1976-1995 (39.3%) than in the group 1996-2014 (28.3%), but more than 50% of all patients were lost to follow-up. Conclusion: Although renal outcome has improved over the investigated last decades, patients with HUS still face a high risk of permanent renal damage. These findings underline the importance of a consequent long-term follow-up in HUS-patients.

Objective: To identify prenatal, perinatal, and postnatal risk factors for dialysis within the first year of life in children with autosomal recessive polycystic kidney disease (ARPKD) as a basis for parental counseling after prenatal and perinatal diagnosis., Study Design: A dataset comprising 385 patients from the ARegPKD international registry study was analyzed for potential risk markers for dialysis during the first year of life., Results: Thirty-six out of 385 children (9.4%) commenced dialysis in the first year of life. According to multivariable Cox regression analysis, the presence of oligohydramnios or anhydramnios, prenatal kidney enlargement, a low Apgar score, and the need for postnatal breathing support were independently associated with an increased hazard ratio for requiring dialysis within the first year of life. The increased risk associated with Apgar score and perinatal assisted breathing was time-dependent and vanished after 5 and 8 months of life, respectively. The predicted probabilities for early dialysis varied from 1.5% (95% CI, 0.5%-4.1%) for patients with ARPKD with no prenatal sonographic abnormalities to 32.3% (95% CI, 22.2%-44.5%) in cases of documented oligohydramnios or anhydramnios, renal cysts, and enlarged kidneys., Conclusions: This study, which identified risk factors associated with onset of dialysis in ARPKD in the first year of life, may be helpful in prenatal parental counseling in cases of suspected ARPKD., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Assisted home dialysis (AHD) is an option to combine the benefits of home dialysis therapy with the needs of dialysis patients who are unable to perform self-treatment at home. While this method is growing in many countries worldwide, no data so far are reported for Germany., Methods: A survey was designed to identify the barriers to the implementation of AHD with the focus on attitudes and beliefs concerning AHD. The survey was sent to all 2060 members of the Germany Society of Nephrology., Results: The response rate was 14% of nephrologists ( n  = 286), representing 24% of all German centres. AHD was regarded as a highly meaningful option (>90% of all responding nephrologists). Fifty-five percent of the centres practice AHD (preferred peritoneal dialysis). The number of treated patients on AHD was small (77% of the centres treat no more than 10 patients). The nephrologists in centres that performed AHD were of older age and the number of dialysis patients treated in these centres was greater. AHD was offered in 57% of centres at chronic kidney disease Stage 4. Inadequate conventional dialysis and patient's request were reasons for choosing AHD. Barriers for offering AHD were lack of reimbursement, shortage of staff, lack of expertise and lack of team motivation., Conclusions: In the view of German nephrologists, AHD is a meaningful method to provide home dialysis care. Inadequate funding and a lack of qualified staff were identified as severe barriers to implementation of AHD. To overcome these barriers and to achieve a higher penetration of AHD, dedicated actions have to be considered. Further studies are needed to prove the AHD concept with regard to outcome effects and cost efficacy.

Background: In patients on conventional hemodialysis (HD), morbidity is high and quality of life is poor. Intensified HD programs have been developed to help overcome these shortcomings, , but very few pediatric dialysis centers have reported the implementation of such a HD program., Methods: An online survey was sent to all 221 pediatric dialysis centers which participate in the International Pediatric Dialysis Network (IPDN). The aim of the survey was to assess the attitude of pediatric nephrologists towards intensified HD, the penetrance of intensified HD into their clinical practice and barriers to implementation., Results: Of the 221 pediatric dialysis centers sent the survey, respondents from 61% (134) replied. Among these respondents, 69% acknowledged being aware of the evidence in support of the use of intensified HD, independent of whether intensified HD was offered at their own center, and 50% associated the use of daily nocturnal HD with the best overall patient outcome. In contrast, only 2% of respondents were in favor of conventional HD. Overall, 38% of the respondents stated that at their center intensified HD is prescribed to a subgroup of patients, most commonly in the form of short daily HD sessions. The most important barriers to expansion of intensified HD programs were lack of adequate funding (66%) and shortage of staff (63%), whereas lack of expertise and of motivation were reported infrequently as obstacles (21 and 14%, respectively)., Conclusion: Intensified HD is considered by many pediatric nephrologists to be the dialysis modality most likely associated with the best patient outcome. The limited use of this treatment approach highlights the importance of defining and successfully addressing the barriers to implementation.

Paediatric palliative care is no longer restricted to patients with cancer and has been extended to patients with other chronic conditions, such as cystic fibrosis or neuromuscular disorders. This review focused on the current state of palliative care for children and adolescents with chronic kidney disease (CKD). We assessed the literature on CKD published up to August 2017. All the papers, except one from 1996, were published this century. This review discusses the role that palliative care plays in the process of decision-making and explores the possibilities of implementing palliative care into the routine therapy of affected patients and providing support for their families. Offering early palliative care as an integral part of the kidney, supportive care provided by the nephrology care team is both necessary and feasible for patients with CKD. As a minimum, a specialised palliative care team should be involved in patients with multiple comorbidities, in conservative treatment scenarios and in acute life-threatening complications. Further studies and guidelines are required to improve the care of patients with CKD and their families., Conclusion: Supportive palliative care should be implemented into the routine care of patients with life-limiting kidney disease., (©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background/aims: Whether the immunosuppressive regimen is associated with micro- and macro-vascular status in pediatric kidney transplant recipients (KTx) is unknown., Methods: We performed a cross-sectional, case-control study in 44 pediatric KTx patients on either everolimus (EVR) plus calcineurin inhibitor or standard treatment, i.e. mycophenolate mofetil plus calcineurin inhibitor. Measurement of carotid intima-media thickness (cIMT) via ultrasound, central pulse wave velocity (PWV) by a cuff-based oscillometric technique, and skin microvascular blood flow during local heating via laser-Doppler-fluximetry (LDF) served as marker of subclinical vascular disease. Serum concentrations of angiopoietin-1 and -2, fibroblast-growth factor 23 (FGF23) and soluble klotho were measured., Results: EVR-treated patients exhibited a similar degree of hypertension, increased cIMT, elevated pro-inflammatory angiopoietin-2, and diminished endothelial survival factor angiopoietin-1 compared to healthy children but presented with a twofold more reduced skin micro-vascular function compared to standard treatment (each p< 0.001). By contrast, PWV and soluble klotho levels were normal in both groups., Conclusion: Endothelial dysfunction seems more frequent in KTx patients on EVR-based immunosuppressive regimen compared to standard immunosuppression., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Objectives: It is known that transition, as a shift of care, marks a vulnerable phase in the adolescents' lives with an increased risk for non-adherence and allograft failure. Still, the transition process of adolescents and young adults living with a kidney transplant in Germany is not well defined. The present research aims to assess transition-relevant structures for this group of young people. Special attention is paid to the timing of the process., Setting: In an observational study, we visited 21 departments of paediatric nephrology in Germany. Participants were doctors (n=19), nurses (n=14) and psychosocial staff (n=16) who were responsible for transition in the relevant centres. Structural elements were surveyed using a short questionnaire. The experiential viewpoint was collected by interviews which were transcribedverbatim before thematic analysis was performed., Results: This study highlights that professionals working within paediatric nephrology in Germany are well aware of the importance of successful transition. Key elements of transitional care are well understood and mutually agreed on. Nonetheless, implementation within daily routine seems challenging, and the absence of written, structured procedures may hamper successful transition., Conclusions: While professionals aim for an individual timing of transfer based on medical, social, emotional and structural aspects, rigid regulations on transfer age as given by the relevant health authorities add on to the challenge., Trial Registration Number: ISRCTN Registry no 22988897; results (phase I) and pre-results (phase II)., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Case Report: We report on a male patient with Tuberous Sclerosis Complex (TSC), which was prenatally diagnosed. At the age of 3 months the patient developed acute renal failure with excessive hyperuricemia. Kidney function improved after rehydration and application of rasburicase, however without full recovery. Due to the inappropriate high levels of uric acid compared to kidney function, screening of hypoxanthine-guanine phosphoribosyltransferase (HPRT) related diseases was initiated. Mutation analysis revealed a deletion of exon 2 and 3 of the HPRT gene confirming the diagnosis of Lesch-Nyhan Disease (LND). After initiation of allopurinol therapy renal function further improved. In the following months the patient developed clinically a typical neurological phenotype of LND and TSC with seizures, severe dystonia and developmental delay., Conclusion: Acute renal failure is a rare complication of HPRT related diseases. Combination of two inherited diseases may lead to a delayed diagnosis due to a mixed and maybe misleading phenotype., (Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Claudin-16 protein (CLDN16) is a component of tight junctions (TJ) with a restrictive distribution so far demonstrated mainly in the kidney. Here, we demonstrate the expression of CLDN16 also in the tooth germ and show that claudin-16 gene (CLDN16) mutations result in amelogenesis imperfecta (AI) in the 5 studied patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). To investigate the role of CLDN16 in tooth formation, we studied a murine model of FHHNC and showed that CLDN16 deficiency led to altered secretory ameloblast TJ structure, lowering of extracellular pH in the forming enamel matrix, and abnormal enamel matrix protein processing, resulting in an enamel phenotype closely resembling human AI. This study unravels an association of FHHNC owing to CLDN16 mutations with AI, which is directly related to the loss of function of CLDN16 during amelogenesis. Overall, this study indicates for the first time the importance of a TJ protein in tooth formation and underlines the need to establish a specific dental follow-up for these patients., (© 2015 American Society for Bone and Mineral Research.)

Transition from child to adult-oriented care is widely regarded a challenging period for young people with kidney transplants and is associated with a high risk of graft failure. We analyzed the existing transition structures in Germany and Austria using a questionnaire and retrospective data of 119 patients transferred in 2011 to 2012. Most centers (73%) confirmed agreements on the transition procedure. Patients' age at transfer was subject to regulation in 73% (18 years). Median age at transition was 18.3 years (16.5-36.7). Median serum creatinine increased from 123 to 132 μmol/L over the 12 month observation period before transfer (P = 0.002). A total of 25/119 patients showed increased creatinine ≥ 20% just before transfer. Biopsy proven rejection was found in 10/119 patients. Three patients lost their graft due to chronic graft nephropathy.Mean coefficient of variation (CoV%) of immunosuppression levels was 0.20 ± 0.1. Increased creatinine levels ≥ 20% just before transfer were less frequently seen in patients with CoV < 0.20 (P = 0.007). The majority of pediatric nephrology centers have internal agreements on transitional care. More than half of the patients had CoV of immunosuppression trough levels consistent with good adherence. Although, 20% of the patients showed increase in serum creatinine close to transfer.

Background: Peritoneal dialysis (PD) or conventional hemodialysis (HD) are considered to be equally efficient dialysis methods in children and adolescents. The aim of our study was to analyze whether an intensified, nocturnal HD program (NHD) is superior to PD in an adolescent cohort., Methods: Thirteen patients were prospectively enrolled in a NHD program. We measured uremia-associated parameters, parameters for nutrition, medication and blood pressure and analyzed the data. These data were compared to those of 13 PD controls, matched for gender, age and weight at the beginning the respective dialysis program and after 6 months of treatment., Results: Serum phosphate levels decreased significantly in the NHD group and remained unchanged in the PD group. Arterial blood pressure in the NHD was significantly lower despite the reduction of antihypertensive treatment, whereas blood pressure levels remained unchanged in the PD controls. Preexisting left ventricular hypertrophy resolved and albumin levels improved with NHD. Dietary restrictions could be lifted for those on NHD, whereas they remained in place for the patients on PD treatment. Residual diuresis remained unchanged after 6 months of either NHD or PD. NHD patients experienced fewer days of hospitalization than the PD controls., Conclusions: Based on our results, NHD results in significantly improved parameters of uremia and nutrition. If individually and logistically possible, NHD should be the treatment modality of preference for older children and adolescents.

Preemptive renal transplantation is the method of choice for end stage renal disease in childhood and adolescence. However, without preemptive transplantation, waiting time for kidney transplantation might exceed several years. The poor quality of life and the extremely high morbidity and mortality rates of dialysis patients have led to the development of intensified hemodialysis programs in which the modes of dialysis (short daily, nocturnal intermittent or daily nocturnal) are different. Such programs have been shown to significantly improve several uremia-associated parameters, such as blood pressure, phosphate control, anemia and growth retardation, in both adult and pediatric (children and adolescents) patients and lead to a reduction in medications, including phosphate binders, erythropoietin and antihypertensive agents. Fluid limitations and dietary restrictions can also be lifted. With respect to psychosocial rehabilitation and quality of life, nocturnal intermittent dialysis programs provide a reasonable compromise of all forms of intensified programs. Experiences and practical approaches of our own in-center nocturnal intermittent hemodialysis program in the light of the recent publications are described in this review.