The mortality rates which we have seen now over several decades of routine provision of renal replacement therapy are truly remarkable – even if, with time, we have become familiar, if not comfortable, with them. The remarkable nature of this mortality issue is its severity, and persistence, despite numerous efforts to combat it with ‘active interventions’. These have included, in no particular order, correction of anaemia, better provision of dialysis adequacy, use of more permeable dialysis membranes, better control of dyslipidaemia, better control of mineral and bone metabolic parameters, correction of hyperhomocysteinaemia, and use of ACE inhibitors. One can now in 2008 be forgiven for some pessimism, nihilism (sometimes known as ‘renalism’) about the prospects for useful prolongation of life on dialysis except of course by transplantation. In this article (a fuller version of which appears also in Nephrology Dialysis and Transplantation, I discuss the reasons for the failure of the trials to date, the likely obstacles to future trials succeeding, and some suggestions for alternative strategies to try to grapple with this immense burden of vascular and all-cause morbidity and mortality.

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