Relationship of phosphorus and calcium-phosphorus product with mortality in CKD

Background: Abnormalities of mineral metabolism are prevalent in patients with kidney failure and are associated with increased risk for cardiovascular events. There are limited data investigating relationships of phosphorus and calcium-phosphorus product with outcomes in patients with chronic kidney disease (CKD) stages 3 to 4. Methods: Serum phosphorus and calcium were measured at baseline in 840 participants from the randomized cohort of the Modification of Diet in Renal Disease Study. Survival status until December 31, 2000, was obtained from the National Death Index. Cox models were performed to assess the relationship of serum phosphorus level and calcium-phosphorus product with all-cause and cardiovascular disease (CVD) mortality. Results: Mean serum phosphorus level was 3.8 ± 0.7 mg/dL (1.23 ± 0.23 mmol/L), calcium-phosphorus product was 34.7 ± 6.3 mg²/dL², and glomerular filtration rate (GFR) was 33 ± 12 mL/min/1.73 m ² (0.55 ± 0.20 mL/s/1.73 m²). All-cause and CVD mortality rates were 25% and 15%. Serum phosphorus level was not related to all-cause mortality in multivariable models (P = 0.46). In unadjusted analysis, serum phosphorus level was associated with (hazard ratio [HR] per 1 mg/dL increase, 1.34; 95% confidence interval [CI], 1.05 to 1.71; P = 0.02) increased risk for CVD mortality, but this association was partly attenuated and not statistically significant after adjustment for GFR and other confounders (HR, 1.27; 95% CI, 0.94 to 1.73; P = 0.12). Calcium-phosphorus product was not associated with all-cause mortality in unadjusted (P = 0.23) or multivariate analysis (P = 0.35). Calcium-phosphorus product was related to CVD mortality in unadjusted (HR per 10 mg²/dL² increase, 1.30; 95% CI, 1.01 to 1.69; P = 0.04) analysis, but this association was not statistically significant after adjustment for GFR and other confounders (HR, 1.22; 95% CI, 0.89 to 1.66; P = 0.23). Conclusion: In the Modification of Diet in Renal Disease Study cohort, serum phosphorus level and calcium-phosphorus product were not statistically associated with all-cause or CVD mortality after adjustment for GFR; however larger studies with additional statistical power are needed to evaluate these relationships, especially in the context of current practice patterns in patients with CKD.