The benefit of reduced serum phosphate levels depends on patient characteristics: a nationwide prospective cohort study.

Abstract

In cohort studies of hyperphosphatemic hemodialysis patients, reduced serum phosphate levels have been linked to a lower mortality risk. To investigate whether this benefit is influenced by patient characteristics, we calculated the number needed to be exposed (NNE), stratified by patient characteristics. In this 9-year prospective cohort study using the nationwide Japanese registry, we enrolled 78256 hemodialysis patients aged 18years or older. We investigated the relationship between time-averaged (TA) phosphate levels and mortality due to cardiovascular disease (CVD) using Cox proportional models. We estimated the 1-year NNE for CVD death in patients with baseline serum phosphate levels ≥6.0mg/dL and exposure to TA phosphate levels decreasing to 3.5-<5.0mg/dL using mixed-effects Poisson models. The hazard ratio of CVD mortality decreased linearly with lower serum TA phosphate levels in those with prior atherosclerotic CVD (ACVD) or diabetic nephropathy (DN) but plateaued with serum phosphate <5.0mg/dL in those without. The hazard ratios (95% confidence interval) for phosphate ≥7.0mg/dL compared with 3.5-<3.9mg/dL were 1.58 (1.38-1.81) in those with prior ACVD, 1.91 (1.68-2.17) in those without, 1.87 (1.63-2.16) in those with DN and 1.65 (1.46-1.87) in those without. However, the NNE for one more person to benefit (NNEB) for CVD death was lower in patients with a history of ACVD than in those without (61 vs 118). Patients with DN had lower NNEB than those without (69 vs 113). In patients with TA albumin ≥3.8g/dL, older patients had lower NNEB, while patients with TA albumin <3.45g/dL showed no benefit in some groups, including the elderly. The benefit of intensive phosphate management may be pronounced in patients with a history of ACVD or DN. A comprehensive approach that considers both age and nutritional status may be necessary when managing serum phosphate levels.