Hyperphosphataemia and related mortality

End-stage renal disease (ESRD) patients have a dramatically higher risk of death compared with the general population [1]. In 1998, Block et al. showed that hyperphosphataemia and a high calcium phosphorus product are independently associated with mortality in dialysis patients [2]. More recently, based on a large cohort, the same authors have confirmed these findings adding hypercalcaemia and severe hyperparathyroidism (HPT) to risk factors for mortality. They have shown that the mortality risk associated with disorders of mineral metabolism is higher than that associated with a low urea reduction ratio (URR) and anaemia [3]. These risk factors for mortality were confirmed in the DOPPS study [4] and more recently in the USRDS waves study [5]. The excess mortality observed in dialysis patients is mainly of cardiovascular origin and it has been associated with cardiovascular calcifications in ESRD patients [6–8]. Non-modifiable risk factors (such as age, diabetes and dialysis vintage) and co-morbid factors (such as hypertension, tobacco use, hyperlipidaemia and chronic inflammation), which are prevalent among dialysis patients, are the main risk factors for increased mortality; disorders of bone mineral metabolism and related treatments are also contributory, as shown by Guerin and London [9,10]. Recently, these authors also pointedout that hyperphosphataemia per se, its associated treatments (calciumbased and aluminium-containing phosphate binders) and complications (parathyroidectomy and adynamic bone disease) are linked to a high prevalence of vascular calcification. However, the underlying relationship between calcium–phosphorus balance and vascular calcification is still unclear. Based on earlier data, the DOQI guidelines for management of bone and mineral disease recommend targets for serum phosphorus level (3.5–5.5mg/dl) and serum calcium phosphorus product (55mg/dl) for calcium corrected for albumin [11]. The general acceptance and wide dissemination of these guidelines enable us to estimate the proportion of patients meeting the guidelines in each country. In the USRDS Dialysis Morbidity and Mortality Study, a HD patient in 1993 had a 53.6% rate of hyperphosphataemia [5]. Bone mineral disorders were reported 10 years later by the DOPPS study (Table 1) [4] and the prevalence of hyperphosphataemia remained high in most countries, with 46.7% of patients having phosphate levels >5.5mg/dl in spite of phosphate binders being used in 80% of patients (DOPPS II). We can conclude from this that current dialysis schedules, dietary interventions and medications are not sufficient to meet the DOQI targets for phosphate. Why? Are the treatments available inadequate or just not powerful enough? Can we improve their use?