Is early chronic kidney disease an important risk factor for cardiovascular disease? A background paper prepared for the UK Consensus Conference on early chronic kidney disease.

Patients with severe chronic kidney disease (CKD) who require renal replacement therapy (RRT), either dialysis or renal transplantation, have a markedly increased risk of cardiovascular disease [1–4]. This increased incidence and prevalence of vascular disease accounts for much of the reduced life expectancy of these patients. The average life expectancy of a 40to 44-year-old white male in the general population in the US is more than 35 years. However, if he is on long-term dialysis he can expect, on average, to live for only eight more years [4]. In Scotland, a patient aged between 20 and 44 on starting renal replacement can expect to survive, on average, a further 16.9 years [5]. Once patients have reached RRT, modification of traditional risk factors such as smoking, obesity, hyperlipidaemia and hypertension may have a disappointing impact upon overall mortality. One of the reasons adduced for this is that by the time RRT is reached it is too late. The burden of years of cardiovascular risk factors appears to overwhelm any intervention. In 1995, in an attempt to improve the quality of life of dialysis patients, the Dialysis Outcomes Quality Initiative (DOQI) was launched by the National Kidney Foundation in the US. In 1997, clinical practice guidelines (DOQI guidelines) were published [6–9]. However, during the development of these guidelines, it became clear that to further improve the quality of life outcomes of patients on dialysis and perhaps impact on the early, persistent, marked and seemingly resistant separation of the survival curves of these patients compared with the general population [10–12] intervention at an earlier stage of progressive CKD was likely to be essential. Therefore, in 1999 the Dialysis Outcomes Quality Initiative became the Kidney Disease Outcomes Quality Initiative (K/DOQI). This resulted in the publication in 2002 of clinical practice guidelines for CKD [3]. During the course of this initiative two factors further shifted the emphasis towards earlier CKD. Firstly, patients with early CKD appeared to have a significantly higher overall mortality and cardiovascular disease burden compared with the general population. Secondly, the majority of patients with CKD died before progressing to renal replacement [13]. A recent large observational study of patients with early CKD followed for 5.5 years found that though only 3.1% progressed to requiring RRT, 24.9% died before reaching dialysis. Cardiovascular Disease (CVD) may have accounted for many of these deaths [14]. This early CKD population deserved attention to their cardiovascular risks in their own right not just to improve the dialysis survival curves of the relative few who progressed to RRT. This excess cardiovascular risk was estimated by the K/DOQI guidelines to be high enough to suggest that ‘All patients with chronic kidney disease should be considered in the ‘‘highest risk’’ group for cardiovascular disease, irrespective of levels of traditional CVD risk factors’ [3]. This, together with the possibility that the optimal management of cardiovascular risk factors in early CKD may in addition delay or reduce progression of CKD, led to increasing interest in identifying CKD earlier and considering modifying these risk factors earlier [3,15]. This aritcle will review the evidence as to whether early CKD is an important risk factor for the presence, severity and progression of CVD. Correspondence to: Conal Daly, Consultant Nephrologist, Renal Unit, Western Infirmary Glasgow, Dumbarton Road, Glasgow, UK. Email: Conal.Daly@NorthGlasgow.Scot. NHS.UK Nephrol Dial Transplant (2007) 22 [Suppl 9]: ix19–ix25