Ratio of Urinary Proteins to Albumin Excretion Shifts Substantially during Progression of the Podocytopathy Alport Syndrome, and Spot Urine Is a Reliable Method to Detect These Pathologic Changes.

The urinary albumin- and protein-to-creatinine ratios (UACR and UPCR, respectively) are key endpoints in most clinical trials assessing risk of progression of chronic kidney disease (CKD). For the first time, the current study compares the UACR versus the UPCR head-to-head at early stages of CKD, taking use of the hereditary podocytopathy Alport syndrome (AS) as a model disease for any CKD. Urine samples originated from the prospective randomized, controlled EARLY PRO-TECT Alport trial (NCT01485978).

Effects of Burosumab Treatment on Mineral Metabolism in Children and Adolescents With X-linked Hypophosphatemia.

Context: Burosumab has been approved for the treatment of children and adults with X-linked hypophosphatemia (XLH). Real-world data and evidence for its efficacy in adolescents are lacking.

Objective: To assess the effects of 12 months of burosumab treatment on mineral metabolism in children (aged <12 years) and adolescents (aged 12-18 years) with XLH.

Prevalence and potential relevance of hyperuricemia in pediatric kidney transplant recipients-a CERTAIN registry analysis.

Background: Asymptomatic hyperuricemia is frequently observed in pediatric kidney transplant recipients; symptomatic hyperuricemia, however, is a rare complication. Only few data are available in this patient population. We, therefore, investigated the prevalence of hyperuricemia and its association with kidney transplant function and blood pressure in a multicenter cohort of pediatric kidney transplant recipients.

Medulloblastoma in Adults: Cytogenetic Phenotypes Identify Prognostic Subgroups.

Adult medulloblastomas (MB) are rare. We investigated the genetic landscape and prognostic impact of genetic aberrations in a cohort of 117 adult medulloblastomas. Histological features and pathway activation were evaluated at the protein level; 14.

Varicella-zoster-virus vaccination of immunosuppressed children with inflammatory bowel disease or autoimmune hepatitis: A prospective observational study.

Background And Aims: Children with inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH) receiving immunosuppressive treatment are at risk for severe varicella zoster virus (VZV)-induced disease. This study evaluated vaccination of susceptible patients with stable disease and documented immunoreactivity without interruption of their current immunosuppression (IS).

Methods: This prospective multicentre observational study used a prevaccination checklist to select patients with low-intensity and high-intensity IS for VZV vaccination.

Precise variant interpretation, phenotype ascertainment, and genotype-phenotype correlation of children in the EARLY PRO-TECT Alport trial.

Early initiation of therapy in patients with Alport syndrome (AS) slows down renal failure by many years. Genotype-phenotype correlations propose that the location and character of the individual's variant correlate with the renal outcome and any extra renal manifestations. In-depth clinical and genetic data of 60/62 children who participated in the EARLY PRO-TECT Alport trial were analyzed.

Nonmetastatic Medulloblastoma of Early Childhood: Results From the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort.

Purpose: The HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy.

Patients And Methods: From 2001-2011, 87 patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for nonresponse or progression.

A multicenter, randomized, placebo-controlled, double-blind phase 3 trial with open-arm comparison indicates safety and efficacy of nephroprotective therapy with ramipril in children with Alport's syndrome.

Children with Alport syndrome develop renal failure early in life. Since the safety and efficacy of preemptive nephroprotective therapy are uncertain we conducted a randomized, placebo-controlled, double-blind trial in 14 German sites of pediatric patients with ramipril for three to six years plus six months follow-up to determine these parameters. Pretreated children and those whose parents refused randomization became an open-arm control, which were compared to prospective real-world data from untreated children.

Twelve-month outcome in juvenile proliferative lupus nephritis: results of the German registry study.

Background: Children presenting with proliferative lupus nephritis (LN) are treated with intensified immunosuppressive protocols. Data on renal outcome and treatment toxicity is scare.

Methods: Twelve-month renal outcome and comorbidity were assessed in 79 predominantly Caucasian children with proliferative LN reported to the Lupus Nephritis Registry of the German Society of Paediatric Nephrology diagnosed between 1997 and 2015.

HNF1B nephropathy has a slow-progressive phenotype in childhood-with the exception of very early onset cases: results of the German Multicenter HNF1B Childhood Registry.

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.

Effects of 1-Methyltryptophan on Immune Responses and the Kynurenine Pathway after Lipopolysaccharide Challenge in Pigs.

An enhanced indoleamine 2,3-dioxygenase 1 (IDO1) activity is associated with an increased mortality risk in sepsis patients. Thus, the preventive inhibition of IDO1 activity may be a promising strategy to attenuate the severity of septic shock. 1-methyltryptophan (1-MT) is currently in the interest of research due to its potential inhibitory effects on IDO1 and immunomodulatory properties.

Impaired Microcirculation in Children After Kidney Transplantation: Everolimus Versus Mycophenolate Based Immunosuppression Regimen.

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.

Effects of growth hormone treatment on adult height in severely short children with X-linked hypophosphatemic rickets.

Background: We recently showed that a 3-year growth hormone (GH) treatment improves linear growth in severely short children with X-linked hypophosphatemic rickets (XLH). It is unknown if GH therapy increases adult height in XLH patients.

Methods: We carried out a follow-up analysis of a randomized controlled open-label GH study in short prepubertal children with XLH on phosphate and active vitamin D treatment.

Comparison of calcimimetic R568 and calcitriol in mineral homeostasis in the Hyp mouse, a murine homolog of X-linked hypophosphatemia.

X-linked hypophosphatemia (XLH) caused by mutations in the Phex gene is the most common human inherited phosphate wasting disorder characterized by enhanced synthesis of fibroblast growth factor 23 (FGF23) in bone, renal phosphate wasting, 1,25(OH)D (1,25D) deficiency, rickets and osteomalacia. Here we studied the effects of calcimimetic R568 and calcitriol treatment in the Hyp mouse, a murine homolog of XLH. We hypothesized that mineral homeostasis is differentially affected by R568 and 1,25D with respect to the PTH-vitamin D-FGF23-Klotho axis and bone health.

Tropomyosin receptor kinase C (TrkC) expression in medulloblastoma: relation to the molecular subgroups and impact on treatment response.

Purpose: High messenger RNA (mRNA) expression of the tropomyosin receptor kinase C gene (TrkC) has been associated with favorable survival in medulloblastoma patients. Untested is whether it plays a role through modulating the response to therapy or whether it might be a surrogate marker for a favorable molecular subgroup.

Methods: The medulloblastoma-derived cell line DAOY was stably transfected to overexpress TrkC (clone DAOY-TrkC) and compared to a control (clone DAOY-EV, empty vector transfected).

Utility of surrogate markers for the prediction of relapses in inflammatory bowel diseases.

Patients with diagnosed inflammatory bowel disease (IBD) will commonly experience a clinical relapse in spite of a prolonged therapy-induced period of clinical remission. The current methods of assessing subclinical levels of low-grade inflammation which predispose patients to relapse are not optimal when considering both cost and patient comfort. Over the past few decades, much investigation has discovered that proteins such as calprotectin that are released from inflammatory cells are capable of indicating disease activity.

Optimizing the process of nucleofection for professional antigen presenting cells.

Background: In times of rapidly increasing numbers of immunological approaches entering the clinics, antigen delivery becomes a pivotal process. The genuine way of rendering antigen presenting cells (APC) antigen specific, largely influences the outcome of the immune response. Short peptides bear the demerit of HLA restriction, whereas the proper way of delivery for long peptide sequences is currently a matter of debate.

Immunoregulatory Role of Myeloid-derived Cells in Inflammatory Bowel Disease.

As the frontiers of immunological research expand, new insights into the pathogenesis of long poorly understood diseases, such as inflammatory bowel disease (IBD), are opening up new possible avenues for treatment. Myeloid-derived cells (i.e.

Cardiovascular risk and mineral bone disorder in patients with chronic kidney disease.

The term chronic kidney disease-mineral bone disorder has been coined recently to highlight that the disturbed mineral and bone metabolism is a major contributor to vascular calcification and finally cardiovascular disease. This syndrome is characterized by clinical, biochemical and/or histological findings, i.e.

Paediatric reference values for the C-terminal fragment of fibroblast-growth factor-23, sclerostin, bone-specific alkaline phosphatase and isoform 5b of tartrate-resistant acid phosphatase.

Background: Paediatric reference values for novel markers of phosphate homeostasis, bone formation and resorption and their putative relationship to growth are lacking.

Methods: A total of 424 healthy children, adolescents and young adults (221 males) aged 0.1-21 y, were enrolled in this cross-sectional study.

Arterial microcalcification in atherosclerotic patients with and without chronic kidney disease: a comparative high-resolution scanning X-ray diffraction analysis.

Vascular calcification, albeit heterogeneous in terms of biological and physicochemical properties, has been associated with ageing, lifestyle, diabetes, and chronic kidney disease (CKD). It is unknown whether or not moderately impaired renal function (CKD stages 2-4) affects the physiochemical composition and/or the formation of magnesium-containing tricalcium phosphate ([Ca,Mg](3)[PO(4)](2), whitlockite) in arterial microcalcification. Therefore, a high-resolution scanning X-ray diffraction analysis (European Synchrotron Radiation Facility, Grenoble, France) utilizing histological sections of paraffin-embedded arterial specimens derived from atherosclerotic patients with normal renal function (n = 15) and CKD (stages 2-4, n = 13) was performed.

Non-small cell lung carcinoma in an adolescent manifested by acute paraplegia due to spinal metastases: a case report.

Introduction: Bronchial carcinomas in childhood and adolescence are extremely rare; only individual cases have been reported previously.

Case Presentation: We report on a 16-year-old Caucasian German boy with non-small cell lung carcinoma (squamous cell non-small cell lung carcinoma) stage IV, T4N2M1, without epidermal growth factor receptor overexpression and/or mutation or k-ras mutation. He presented with paraplegia due to spinal metastases of the bronchial carcinoma.