Familial hypercholesterolemia (FH) is a dominantly inherited disorder present from birth that markedly elevates plasma low-density lipoprotein cholesterol and causes premature coronary heart disease. There are at least 20 million people with FH worldwide, but the majority remains undetected, and current treatment is often suboptimal. To address this major gap in coronary prevention we present, from an international perspective, consensus-based guidance on the care of FH. The guidance was generated from seminars and workshops held at an international symposium. The recommendations focus on the detection, diagnosis, assessment, and management of FH in adults and children and set guidelines for clinical purposes. They also refer to best practice for cascade screening and risk notifying and testing families for FH, including use of genetic testing. Guidance on treatment is based on risk stratification, management of noncholesterol risk factors, and the safe and effective use of low-density lipoprotein-lowering therapies. Recommendations are given on lipoprotein apheresis. The use of emerging therapies for FH is also foreshadowed. This international guidance acknowledges evidence gaps but aims to make the best use of contemporary practice and technology to achieve the best outcomes for the care of FH. It should accordingly be used to inform clinical judgment and be adjusted for country-specific and local healthcare needs and resources.
Familial hypercholesterolaemia (FH) is a dominantly inherited disorder present from birth that markedly elevates plasma low-density lipoprotein (LDL) cholesterol and causes premature coronary heart disease. There are at least 20 million people with FH worldwide, but the majority remains undetected and current treatment is often suboptimal.To address this major gap in coronary prevention we present, from an international perspective, consensus-based guidance on the care of FH. The guidance was generated from seminars and workshops held at an international symposium. The recommendations focus on the detection, diagnosis, assessment and management of FH in adults and children, and set guidelines for clinical purposes. They also refer to best practice for cascade screening and risk notifying and testing families for FH, including use of genetic testing. Guidance on treatment is based on risk stratification, management of non-cholesterol risk factors and safe and effective use of LDL lowering therapies. Recommendations are given on lipoprotein apheresis. The use of emerging therapies for FH is also foreshadowed.This international guidance acknowledges evidence gaps, but aims to make the best use of contemporary practice and technology to achieve the best outcomes for the care of FH. It should accordingly be employed to inform clinical judgment and be adjusted for country-specific and local healthcare needs and resources.
The effect of peritoneal dialysates with low-glucose degradation products on peritoneal membrane morphology is largely unknown, with functional relevancy predominantly derived from experimental studies. To investigate this, we performed automated quantitative histomorphometry and molecular analyses on 256 standardized peritoneal and 172 omental specimens from 56 children with normal renal function, 90 children with end-stage kidney disease at time of catheter insertion, and 82 children undergoing peritoneal dialysis using dialysates with low-glucose degradation products. Follow-up biopsies were obtained from 24 children after a median peritoneal dialysis of 13 months. Prior to dialysis, mild parietal peritoneal inflammation, epithelial-mesenchymal transition and vasculopathy were present. After up to six and 12 months of peritoneal dialysis, blood microvessel density was 110 and 93% higher, endothelial surface area per peritoneal volume 137 and 95% greater, and submesothelial thickness 23 and 58% greater, respectively. Subsequent peritoneal changes were less pronounced. Mesothelial cell coverage was lower and vasculopathy advanced, whereas lymphatic vessel density was unchanged. Morphological changes were accompanied by early fibroblast activation, leukocyte and macrophage infiltration, diffuse podoplanin presence, epithelial mesenchymal transdifferentiation, and by increased proangiogenic and profibrotic cytokine abundance. These transformative changes were confirmed by intraindividual comparisons. Peritoneal microvascular density correlated with peritoneal small-molecular transport function by uni- and multivariate analysis. Thus, in children on peritoneal dialysis neutral pH dialysates containing low-glucose degradation products induce early peritoneal inflammation, fibroblast activation, epithelial-mesenchymal transition and marked angiogenesis, which determines the PD membrane transport function.