Introduction to epigenetic inheritance: Definition, mechanisms, implications and relevance.

Complex phenotypes result from the interaction between genetic and environmental informations. Almost a decade ago, the discovery of acquired epigenetic inheritance has shown that individual’s environmental experiences can influence developmental and phenotypic trajectories across several generations. The field is now starting to unveil the molecular mechanisms, while its relevance for complex disease risk and adaptive evolution is still unclear and strongly debated. The aim of this chapter is to introduce the reader to the concept of epigenetic inheritance, provide an overview on the underlying molecular determinants and highlight its potential relevance for individual’s susceptibility to complex, non-mendelian, diseases

The current and future landscape of dialysis

The development of dialysis by early pioneers such as Willem Kolff and Belding Scribner set in motion several dramatic changes in the epidemiology, economics and ethical frameworks for the treatment of kidney failure. However, despite a rapid expansion in the provision of dialysis - particularly haemodialysis and most notably in high-income countries (HICs) - the rate of true patient-centred innovation has slowed. Current trends are particularly concerning from a global perspective: current costs are not sustainable, even for HICs, and globally, most people who develop kidney failure forego treatment, resulting in millions of deaths every year. Thus, there is an urgent need to develop new approaches and dialysis modalities that are cost-effective, accessible and offer improved patient outcomes. Nephrology researchers are increasingly engaging with patients to determine their priorities for meaningful outcomes that should be used to measure progress. The overarching message from this engagement is that while patients value longevity, reducing symptom burden and achieving maximal functional and social rehabilitation are prioritized more highly. In response, patients, payors, regulators and health-care systems are increasingly demanding improved value, which can only come about through true patient-centred innovation that supports high-quality, high-value care. Substantial efforts are now underway to support requisite transformative changes. These efforts need to be catalysed, promoted and fostered through international collaboration and harmonization. Dialysis is a life-saving therapy; however, costs of dialysis are high, access is inequitable and outcomes are inadequate. This Review describes the current landscape of dialysis therapy from an epidemiological, economic, ethical and patient-centred framework, and describes initiatives that are aimed at stimulating innovations in the field to one that supports high-quality, high-value care