Relationship between serum phosphorus and mortality in non-dialysis chronic kidney disease patients: evidence from NHANES 2001–2018

Background: Hyperphosphatemia is common in chronic kidney disease (CKD), associated with higher mortality in dialysis patients. Its impact in non-dialysis patients, especially those with preserved kidney function, remains uncertain. Methods: A prospective cohort study was conducted using data from the National Health and Nutrition Examination Survey (2001–2008). Serum phosphorus was analyzed as a continuous variable, or categorized into three groups: < 3.5 mg/dL, 3.5 to < 4.5 mg/dL, and ≥ 4.5 mg/dL. Cox proportional hazards models were used to analyze the association between phosphorus with all-cause and cardiovascular disease (CVD) mortality, with or without adjustment for age, sex, race, hemoglobin, estimated glomerular filtration rate (eGFR), serum albumin, serum calcium, 25(OH)D, obesity, hypertension, diabetes, and CVD. Results: A total of 7694 participants were included in the analysis, representing 28 million CKD patients in the United States. During mean 92 months of follow up, 2708 all-cause deaths (including 969 CVD deaths) were observed. Per 1 mg/dL increase in phosphorus was associated with a 13% and 24% increased risk of all-cause mortality (hazard ratio [HR], 1.13; 95%CI, 1.02–1.24) and CVD mortality (HR, 1.24; 95%CI, 1.07–1.45), respectively. Compared with the < 3.5 mg/dL, phosphorus ≥ 4.5 mg/dL was associated with a 28% and 57% increased risk of all-cause mortality (HR, 1.28; 95%CI, 1.05–1.55) and CVD mortality (HR, 1.57; 95CI, 1.19–2.08), respectively. In participants with eGFR < 60 ml/min/1.73m, elevated phosphorus (≥ 4.5 mg/ dL) were significantly associated with increased risk of all-cause mortality (HR, 1.36; 95%CI, 1.07–1.72). No significant association was observed in eGFR ≥ 60 ml/min/1.73m group (HR, 1.31; 95%CI, 0.86–1.99). This correlation does not differ significantly between subgroups defined by eGFR level (P for interaction = 0.889). Conclusion: Serum phosphorus above 4.5 mg/dL is significantly associated with a 28% and 57% increased risk of all-cause and CVD death in non-dialysis CKD patients, respectively. This relationship still demonstrated in patients with eGFR < 60 ml/min/1.73m. However, for population with eGFR ≥ 60 ml/min/1.73m, further verification is needed.