Association between serum phosphate levels within the normal range and all-cause mortality among US adults

Hyperphosphatemia is associated with increased mortality in chronic kidney disease (CKD), but the clinical relevance of variation within the normal serum phosphate range remains unclear. This study evaluated the association between higher-normal serum phosphate levels within the normal range and all-cause mortality among US adults.

We conducted a cohort study using data from 15 848 individuals aged ≥20 years with serum phosphate levels between 2.5 and 4.5 mg/dL from the Third National Health and Nutrition Examination Survey (1988-1994) linked to mortality data ascertained by the National Center for Health Statistics with the National Death Index through December 2019. Baseline serum phosphate was the exposure. Participants were categorized into lower-normal (2.5 mg/dL to <3.5 mg/dL; n = 7691) and higher-normal (3.5 mg/dL to ≤4.5 mg/dL; n = 8157) serum phosphate groups. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) for all-cause mortality. A subgroup analysis was conducted by CKD status (estimated glomerular filtration rate ≥60 and <60 mL/min/1.73 m²).

Over a median follow-up of 26.3 years, 6660 (42%) participants died. Compared to the lower-normal group, the higher-normal group showed no significant increase in all-cause mortality risk in the overall population (aHR 1.06 [95% CI, 0.98-1.13]). However, among individual with CKD, higher-normal serum phosphate was significantly associated with increased all-cause mortality (aHR 1.13 [95% CI, 1.02-1.25]), wheres no association was observed in those with estimated glomerular filtration rate ≥60 mL/min/1.73 m² (aHR 1.01 [95% CI, 0.92-1.12]; P for interaction, .14).

Higher-normal phosphate levels were associated with an increased risk of all-cause mortality among people with CKD.