CHD1L: a new candidate gene for congenital anomalies of the kidneys and urinary tract (CAKUT)

Background. Recently, we identified a microduplication in chromosomal band 1q21.1 encompassing the CHD1L/ALC1 gene encoding a chromatin-remodelling enzyme in congenital anomalies of the kidneys and urinary tract (CAKUT) patient. Methods. To explore the role of CHD1L in CAKUT, we screened 85 CAKUT patients for mutations in the CHD1L gene and performed functional analyses of the three heterozygous missense variants detected. In addition, we quantitatively determined CHD1L expression in multiple human fetal and adult tissues and analysed expression of CHD1L protein in human embryonal, adult and hydronephrotic kidney sections. Results. Two of three novel heterozygous missense variants identified in three patients were not found in >400 control chromosomes. All variants lead to amino acid substitutions in or near the CHD1L macro domain, a poly-ADP-ribose (PAR)-binding module interacting with PAR polymerase 1 (PARP1), and showed decreased interaction with PARP1 by pull-down assay of transfected cell lysates. Quantitative messenger RNA analysis demonstrated high CHD1L expression in human fetal kidneys, and levels were four times higher than in adult kidneys. In the human embryo at 7-11 weeks gestation, CHD1L immunolocalized in the early ureteric bud and the S- and comma-shaped bodies, critical stages of kidney development. In normal postnatal sections, CHD1L was expressed in the cytoplasm of tubular cells in all tubule segments. CHD1L expression appeared higher in the hydronephrotic kidney of one patient with a hypofunctional CHD1L variant than in normal kidneys, recapitulating high fetal levels. Conclusion. Our data suggest that CHD1L plays a role in kidney development and may be a new candidate gene for CAKU

The limits of partial life cycle assessment studies in road construction practices: A case study on the use of hydrated lime in Hot Mix Asphalt

Extensive published literature shows that hydrated lime improves Hot Mix Asphalt (HMA) durability. Its impact on the environmental impact of HMA has not been investigated. This paper presents a comparative Life Cycle Assessment (LCA) for the use of HMA without hydrated lime (classical HMA) and with hydrated lime (modified HMA) for the lifetime of a highway. System boundaries cover the life cycle from cradle-to-grave, meaning extraction of raw materials to end of life of the road. The main assumptions were: 1. Lifetime of the road 50 years; 2. Classical HMA with a life span of 10 years, maintenance operations every 10 years; 3. Modified HMA with an increase in the life span by 25%, maintenance operations every 12.5 years. For the lifetime of the road, modified HMA has the lowest environmental footprint compared to classical HMA with the following benefits: 43% less primary total energy consumption resulting in 23% lower emissions of greenhouse gases. Partial LCAs focusing only on the construction and/or maintenance phase should be used with caution since they could lead to wrong decisions if the durability and the maintenance scenarios differ. Sustainable construction technologies should not only consider environmental impact as quantified by LCA, but also economic and social impacts as well. Avoiding maintenance steps means less road works, fewer traffic jams and hence less CO2 emissions

CHD1L: a new candidate gene for congenital anomalies of the kidneys and urinary tract (CAKUT)

Recently, we identified a microduplication in chromosomal band 1q21.1 encompassing the CHD1L/ALC1 gene encoding a chromatin-remodelling enzyme in congenital anomalies of the kidneys and urinary tract (CAKUT) patient

Mortality risk disparities in children receiving chronic renal replacement therapy for the treatment of end-stage renal disease across Europe: an ESPN-ERA/EDTA registry analysis

Item does not contain fulltextBACKGROUND: We explored the variation in country mortality rates in the paediatric population receiving renal replacement therapy across Europe, and estimated how much of this variation could be explained by patient-level and country-level factors. METHODS: In this registry analysis, we extracted patient data from the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry for 32 European countries. We included incident patients younger than 19 years receiving renal replacement therapy. Adjusted hazard ratios (aHR) and the explained variation were modelled for patient-level and country-level factors with multilevel Cox regression. The primary outcome studied was all-cause mortality while on renal replacement therapy. FINDINGS: Between Jan 1, 2000, and Dec 31, 2013, the overall 5 year renal replacement therapy mortality rate was 15.8 deaths per 1000 patient-years (IQR 6.4-16.4). France had a mortality rate (9.2) of more than 3 SDs better, and Russia (35.2), Poland (39.9), Romania (47.4), and Bulgaria (68.6) had mortality rates more than 3 SDs worse than the European average. Public health expenditure was inversely associated with mortality risk (per SD increase, aHR 0.69, 95% CI 0.52-0.91) and explained 67% of the variation in renal replacement therapy mortality rates between countries. Child mortality rates showed a significant association with renal replacement therapy mortality, albeit mediated by macroeconomics (eg, neonatal mortality reduced from 1.31 [95% CI 1.13-1.53], p=0.0005, to 1.21 [0.97-1.51], p=0.10). After accounting for country distributions of patient age, the variation in renal replacement therapy mortality rates between countries increased by 21%. INTERPRETATION: Substantial international variation exists in paediatric renal replacement therapy mortality rates across Europe, most of which was explained by disparities in public health expenditure, which seems to limit the availability and quality of paediatric renal care. Differences between countries in their ability to accept and treat the youngest patients, who are the most complex and costly to treat, form an important source of disparity within this population. Our findings can be used by policy makers and health-care providers to explore potential strategies to help reduce these health disparities. FUNDING: ERA-EDTA and ESPN

The European Society for Paediatric Nephrology study of pediatric renal care in Europe: comparative analysis 1998-2017

BACKGROUND: In 1998, a survey of the European Society for Paediatric Nephrology (ESPN) revealed substantial disparities in pediatric renal care among European countries. Therefore, ESPN aimed at harmonizing renal care in all European countries in the following 20 years. In 2017, we conducted a survey to evaluate the current status of renal health policies for children in Europe. METHODS: A 33-question web-based survey was designed and sent to presidents or representatives of national societies of pediatric nephrology in 44 European countries. RESULTS: Data was reported from 42 (95.5%) countries. The number of pediatric nephrologists per million child population increased from 1998 to 2017 in 70% of countries. Pediatric dialysis facilities for acute kidney injury and end-stage kidney disease were available in 95% of countries. The availability of pediatric kidney transplantation increased from 55 to 93% of countries. Considerable variation was found in the current availability of allied health professionals, including psychosocial and nutritional support, high-tech diagnostic methods, and treatment with expensive drugs for children with kidney diseases between different European countries. CONCLUSIONS: The 20-year follow-up analysis of pediatric renal care services in European countries revealed that pediatric nephrology has become a well-established subspecialty in pediatrics and nephrology in 2017. The ESPN will continue its efforts to further improve pediatric renal care for European children by harmonizing remaining disparities of renal care services.status: publishe