High plasma phosphate as a risk factor for decline in renal function and mortality in pre-dialysis patients

Hyperphosphataemia is associated with increased mortality in patients with chronic kidney disease (CKD) stage IV or on dialysis. Furthermore, in animal studies, elevated plasma phosphate has been shown to be associated with an accelerated decline in renal function. The aim of this study was to determine the association of plasma phosphate with renal function loss and mortality in CKD stage IV-V pre-dialysis patients with GFR <20 ml/min/1.73 m(2).

Incident pre-dialysis patients were included between 1999 and 2001 in the multi-centre PREPARE study, and followed until 2003 or death. Rate of decline in renal function for each patient was calculated by linear regression using the Modification of Diet in Renal Disease (MDRD) formula to estimate GFR (eGFR).

A total of 448 patients were included [mean (SD) age 60 (15) years, eGFR 13 (5.4) ml/min/1.73 m(2), decline in renal function 0.38 (0.95) ml/min/month]. Phosphate concentration at baseline was 4.71 (1.16) mg/dl, calcium 9.25 (0.77) mg/dl and calcium-phosphate product 43.5 (10.9) mg(2)/dl(2). For each mg/dl higher phosphate concentration, the mean (95% CI) decline in renal function increased with 0.154 (0.071-0.237) ml/min/month. After adjustment, this association remained [beta 0.178 (0.082-0.275)]. Seven percent of the patients died. Crude mortality risk was 1.25 (0.85-1.84) per mg/dl increase in phosphate, which increased to 1.62 (1.02-2.59) after adjustment.

High plasma phosphate is an independent risk factor for a more rapid decline in renal function and a higher mortality during the pre-dialysis phase. Plasma phosphate within the normal range is likely of vital importance in pre-dialysis patients.