Publications by authors named "Levtchenko E"

X-linked hypophosphataemia (XLH) is a rare metabolic bone disorder caused by pathogenic variants in the PHEX gene, which is predominantly expressed in osteoblasts, osteocytes and odontoblasts. XLH is characterized by increased synthesis of the bone-derived phosphaturic hormone fibroblast growth factor 23 (FGF23), which results in renal phosphate wasting with consecutive hypophosphataemia, rickets, osteomalacia, disproportionate short stature, oral manifestations, pseudofractures, craniosynostosis, enthesopathies and osteoarthritis. Patients with XLH should be provided with multidisciplinary care organized by a metabolic bone expert.

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Dent disease is a rare X-linked tubulopathy that is characterized by low-molecular-weight (LMW) proteinuria associated with hypercalciuria, which may lead to nephrolithiasis, nephrocalcinosis, and kidney failure between the 3rd and the 5th decades of life in 30-80% of affected males. The disease is most often associated with various manifestations of proximal tubular dysfunction. Affected individuals may present nephrotic range proteinuria which may be misinterpreted and cause diagnostic delay.

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Background: There is a lack of information on the current healthcare systems for children with kidney diseases across Europe. The aim of this study was to explore the different national approaches to the organization and delivery of pediatric nephrology services within Europe.

Methods: In 2020, the European society for Paediatric Nephrology (ESPN) conducted a cross-sectional survey to identify the existing pediatric nephrology healthcare systems in 48 European countries covering a population of more than 200 million children.

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Introduction: Apolipoprotein L1 (APOL1) risk variants (G1, G2) are known to enhance the protective ability against human African trypanosomiasis (HAT), in addition to their role in kidney and cardiovascular disease. The effects of these variants on trypanosome infection could differ regionally owing to local adaptations of the host and pathogen. This study explored APOL1 risk variants distribution in HAT-infected and non-infected populations from a rural Trypanosoma brucei gambiense (T.

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Background: Steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) significantly affect children's quality of life. There are frequent relapses in SSNS and progression in SRNS. IPNA guidelines suggest that monoclonal antibodies like rituximab (RTX) are promising treatments.

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Background: C3 glomerulopathy is a rare clinical entity characterized by dysregulation of the alternative complement pathway in glomerular disease. Studies defining the natural history of C3G in the pediatric population are scarce.

Methods: Patients included in this retrospective study were diagnosed between 2011 and 2020 in 12 European pediatric nephrology units.

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Congenital nephrogenic diabetes insipidus (NDI; also known as arginine vasopressin resistance) is a rare inherited disorder of water homeostasis, caused by insensitivity of the distal nephron to arginine vasopressin. Consequently, the kidney loses its ability to concentrate urine, which leads to polyuria, polydipsia and the risk of hypertonic dehydration. The diagnosis and management of NDI are very challenging and require an integrated, multidisciplinary approach.

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Article Synopsis
  • The study investigates the role of a protein called CCDC158 in kidney function, specifically in the reabsorption of proteins in the renal proximal tubules, highlighting its importance in kidney and reproductive health.
  • Whole exome sequencing identified a missense variant in CCDC158 in a male patient with kidney issues, which also appeared in a sister with similar symptoms, suggesting a hereditary component.
  • Functional analyses showed that CCDC158 likely interacts with other proteins involved in endocytosis, affecting kidney function and contributing to conditions like proteinuria and oligospermia, but further research is needed to clarify its exact mechanisms.
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Schimke immuno-osseous-dysplasia (SIOD) is an autosomal recessive systemic disease due to pathogenic variants in SMARCAL1. Manifestations include nephrotic syndrome (NS), kidney failure, T-cell dysfunction, vaso-occlusive disease, and disproportionate short stature, a general feature of this disease. Here, we present a markedly different growth pattern in two brothers with SIOD sharing the same homozygous R561C missense variant.

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Article Synopsis
  • Personalized disease models are essential for testing treatments on diseased cells, particularly innovative therapies, and this study focuses on extracellular vesicles (EVs) from kidney progenitor cells (nKPCs) as a potential treatment for steroid-resistant nephrotic syndrome in children.
  • Urinary podocytes from affected patients were treated with nKPC-EVs and compared to standard drugs, showing that nKPC-EVs significantly reduced permeability in podocytes, while standard treatments had limited effectiveness.
  • RNA sequencing identified the upregulation of two genes, SUMO1 and SENP2, linked to the treatment's effectiveness, suggesting that the SUMOylation pathway plays a crucial role in the therapeutic impact of nKPC-EVs
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Background: Focal segmental glomerulosclerosis (FSGS) is a histological pattern of glomerular damage that includes idiopathic conditions as well as genetic and non-genetic forms. Among these various etiologies, different phenotypes within the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT) have been associated with FSGS.

Summary: Until recently, the main pathomechanism of how congenital kidney and urinary tract defects lead to FSGS was attributed to a reduced number of nephrons, resulting in biomechanical stress on the remaining glomeruli, detachment of podocytes, and subsequent inability to maintain normal glomerular architecture.

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Glomerular hyperfiltration and albuminuria are frequent kidney abnormalities in children with sickle cell anaemia (SCA). However, little is known about their persistence in African SCA children. This prospective study included 600 steady-state SCA children aged 2-18 years from the Democratic Republic of Congo.

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Article Synopsis
  • - X-linked hypophosphatemia (XLH) is a rare disorder caused by high levels of FGF23, leading to phosphate loss and decreased vitamin D production, while burosumab is a treatment that helps restore phosphate levels by inhibiting FGF23.
  • - This post-authorization safety study (PASS) monitors the long-term safety of burosumab in children and adolescents aged 1-17 years, with this first interim analysis focusing on the initial safety outcomes based on registry data.
  • - The analysis involved 67 participants, with 37.3% reporting at least one adverse event, primarily musculoskeletal issues; however, there were no serious adverse events or treatment withdrawals, indicating that the safety profile of
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Cystinosis is a rare, autosomal recessive, lysosomal storage disease caused by mutations in the gene , leading to cystine accumulation in the lysosomes. While cysteamine lowers the cystine levels, it does not cure the disease, suggesting that CTNS exerts additional functions besides cystine transport. This study investigated the impact of infantile and juvenile mutations with discrepant genotype/phenotype correlations on CTNS expression, and subcellular localisation and function in clinically relevant cystinosis cell models to better understand the link between genotype and CTNS function.

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Background: Cystine-depleting therapy in nephropathic cystinosis is currently monitored via the white blood cell cystine assay, although its application and usefulness are limited by practical and technical issues. Therefore, alternative biomarkers that are widely available, more economical and less technically demanding, while reliably reflecting long-term adherence to cysteamine treatment, are desirable. Recently, we proposed chitotriosidase enzyme activity as a potential novel biomarker for the therapeutic monitoring of cysteamine treatment in cystinosis.

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Preterm birth, defined as birth before the gestational age of 37 weeks, affects 11% of the newborns worldwide. While extensive research has focused on the immediate complications associated with prematurity, emerging evidence suggests a link between prematurity and the development of kidney disease later in life. It has been demonstrated that the normal course of kidney development is interrupted in infants born prematurely, causing an overall decrease in functional nephrons.

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Article Synopsis
  • The Schwartz equation is widely used to estimate GFR in European children, but its applicability for African children remains uncertain.
  • A study involving 513 African children found that normalizing serum creatinine using European Q-values was effective, with 93.4% of participants falling within the reference range.
  • Among various equations tested, the FAS-Age formula was the most reliable as it showed no dependency on age or sex and does not require height measurements.
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Cystinosis is an autosomal recessive lysosomal storage disorder, caused by mutations in the gene, resulting in an absent or altered cystinosin (CTNS) protein. Cystinosin exports cystine out of the lysosome, with a malfunction resulting in cystine accumulation and a defect in other cystinosin-mediated pathways. Cystinosis is a systemic disease, but the kidneys are the first and most severely affected organs.

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Article Synopsis
  • * Patients and families often face significant psychological and social difficulties, requiring support from psychologists and social workers, many of whom lack expertise in this specific disorder.
  • * A committee of experts developed key insights and practical advice on addressing the psychosocial challenges associated with cystinosis, based on collective agreement due to the limited evidence available for rare diseases.
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Background: Personalized disease models are crucial for assessing the specific response of diseased cells to drugs, particularly novel biological therapeutics. Extracellular vesicles (EVs), nanosized vesicles released by cells for intercellular communication, have gained therapeutic interest due to their ability to reprogram target cells. We here utilized urinary podocytes obtained from children affected by steroid-resistant nephrotic syndrome with characterized genetic mutations as a model to test the therapeutic potential of EVs derived from kidney progenitor cells.

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Cystinosis is a rare, inherited, lysosomal storage disorder characterized by the progressive accumulation of intralysosomal cystine and subsequent organ and tissue damage. The kidneys are the first and most severely impacted organ. Although cystinosis was once considered a fatal pediatric disease, patients with cystinosis are living well into adulthood with advances in medical care, including kidney transplant and early and continuous use of cysteamine therapy.

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Background: Primary, secondary and tertiary healthcare services in Europe create complex networks covering pediatric subspecialties, sociology, economics and politics. Two surveys of the European Society for Paediatric Nephrology (ESPN) in 1998 and 2017 revealed substantial disparities of kidney care among European countries. The purpose of the third ESPN survey is to further identify national differences in the conceptualization and organization of European pediatric kidney health care pathways during and outside normal working hours.

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Messenger RNA (mRNA) therapies are emerging in different disease areas, but have not yet reached the kidney field. Our aim was to study the feasibility to treat the genetic defect in cystinosis using synthetic mRNA in cell models and ctns zebrafish embryos. Cystinosis is a prototype lysosomal storage disorder caused by mutations in the CTNS gene, encoding the lysosomal cystine-H symporter cystinosin, and leading to cystine accumulation in all cells of the body.

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Background: Nephropathic cystinosis (NC) is a rare lysosomal disease, leading to early kidney failure and extra-renal comorbidities. Its prognosis strongly relies on early diagnosis and treatment by cysteamine. Developing economies (DEing) face many challenges when treating patients for rare and chronic diseases.

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