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

Background: 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.

Methods: In this 9-year prospective cohort study using the nationwide Japanese registry, we enrolled 78 256 hemodialysis patients aged 18 years 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 ≥6.0 mg/dL and exposure to TA phosphate levels decreasing to 3.5-<5.0 mg/dL using mixed-effects Poisson models.

Results: 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 <5.0 mg/dL in those without. The hazard ratios (95% confidence interval) for phosphate ≥7.0 mg/dL compared with 3.5-<3.9 mg/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 ≥3.8 g/dL, older patients had lower NNEB, while patients with TA albumin <3.45 g/dL showed no benefit in some groups, including the elderly.

Conclusions: 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.