First genetic analysis of aneurysm genes in familial and sporadic abdominal aortic aneurysm

Genetic causes for abdominal aortic aneurysm (AAA) have not been identified and the role of genes associated with familial thoracic aneurysms in AAA has not been explored. We analyzed nine genes associated with familial thoracic aortic aneurysms, the vascular Ehlers–Danlos gene COL3A1 and the MTHFR p.Ala222Val variant in 155 AAA patients. The thoracic aneurysm genes selected for this study were the transforming growth factor-beta pathway genes EFEMP2, FBN1, SMAD3, TGBF2, TGFBR1, TGFBR2, and the smooth muscle cells genes ACTA2, MYH11 and MYLK. Sanger sequencing of all coding exons and exon–intron boundaries of these genes was performed. Patients with at least one first-degree relative with an aortic aneurysm were classified as familial AAA (n = 99), the others as sporadic AAA. We found 47 different rare heterozygous variants in eight genes: two pathogenic, one likely pathogenic, twenty-one variants of unknown significance (VUS) and twenty-three unlikely pathogenic variants. In familial AAA we found one pathogenic and segregating variant (COL3A1 p.Arg491X), one likely pathogenic and segregating (MYH11 p.Arg254Cys), and fifteen VUS. In sporadic patients we found one pathogenic (TGFBR2 p.Ile525Phefs*18) and seven VUS. Thirteen patients had two or more variants. These results show a previously unknown association and overlapping genetic defects between AAA and familial thoracic aneurysms, indicating that genetic testing may help to identify the cause of familial and sporadic AAA. In this view, genetic testing of these genes specifically or in a genome-wide approach may help to identify the cause of familial and sporadic AAA. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00439-015-1567-0) contains supplementary material, which is available to authorized users

Reducing the costs of chronic kidney disease while delivering quality health care : a call to action

The treatment of chronic kidney disease (CKD) and of end-stage renal disease (ESRD) imposes substantial societal costs. Expenditure is highest for renal replacement therapy (RRT), especially in-hospital haemodialysis. Redirection towards less expensive forms of RRT (peritoneal dialysis, home haemodialysis) or kidney transplantation should decrease financial pressure. However, costs for CKD are not limited to RRT, but also include nonrenal health-care costs, costs not related to health care, and costs for patients with CKD who are not yet receiving RRT. Even if patients with CKD or ESRD could be given the least expensive therapies, costs would decrease only marginally. We therefore propose a consistent and sustainable approach focusing on prevention. Before a preventive strategy is favoured, however, authorities should carefully analyse the cost to benefit ratio of each strategy. Primary prevention of CKD is more important than secondary prevention, as many other related chronic diseases, such as diabetes mellitus, hypertension, cardiovascular disease, liver disease, cancer, and pulmonary disorders could also be prevented. Primary prevention largely consists of lifestyle changes that will reduce global societal costs and, more importantly, result in a healthy, active, and long-lived population. Nephrologists need to collaborate closely with other sectors and governments, to reach these aims