Association of serum phosphorus concentration with mortality in elderly and nonelderly hemodialysis patients

Abstract

Objective: Hypo- and hyperphosphatemia have each been associated with increased mortality in maintenance hemodialysis (MHD) patients. There has not been previous evaluation of a differential relationship between serum phosphorus level and death risk across varying age groups in MHD patients.

Design and settings: In a 6-year cohort of 107,817 MHD patients treated in a large dialysis organization, we examined the association between serum phosphorus levels with all-cause and cardiovascular mortality within 5 age categories (15 to <45, 45 to <65, 65 to <70, 70 to <75, and ≥75 years old) using Cox proportional hazards models adjusted for case-mix covariates and malnutrition inflammation complex syndrome (MICS) surrogates.

Main outcome measure: All-cause and cardiovascular mortality.

Results: The overall mean age of the cohort was 60 ± 16 years, among whom there were 45% women, 35% Blacks, and 58% diabetics. The time-averaged serum phosphorus level (mean ± SD) within each age category was 6.26 ± 1.4, 5.65 ± 1.2, 5.26 ± 1.1, 5.11 ± 1.0, and 4.88 ± 1.0 mg/dL, respectively (P for trend <.001). Hyperphosphatemia (>5.5 mg/dL) was consistently associated with increased all-cause and cardiovascular mortality risks across all age categories, including after adjustment for case-mix and MICS-related covariates. In fully adjusted models, a low serum phosphorus level (<3.5 mg/dL) was associated with increased all-cause mortality only in elderly MHD patients ≥65 years old (hazard ratio [95% confidence interval]: 1.21 [1.07-1.37], 1.13 [1.02-1.25], and 1.28 [1.2-1.37] for patients 65 to <70, 70 to <75, and ≥75 years old, respectively), but not in younger patients (<65 years old). A similar differential cardiovascular mortality risk for low serum phosphorus levels between old and young age groups was observed.

Conclusions: The association between hyperphosphatemia and mortality is similar across all age groups of MHD patients, whereas hypophosphatemia is associated with increased mortality only in elderly MHD patients. Preventing very low serum phosphorus levels in elderly dialysis patients may be associated with better outcomes, which needs to be examined in future studies.

Figure 1

Time-averaged serum phosphorus levels in 107,817 maintenance hemodialysis patients according to age category and sex.

Figure 2

Restricted cubic spline models adjusted for case-mix and malnutrition inflammation complex syndrome surrogates representing logistic regression odds ratio of high serum phosphorus levels (phosphorus≥5.5 mg/dL) (A) and low serum phosphorus levels (phosphorus<3.5 mg/dL) (B). Fully adjusted cubic spline models include adjustment for age, gender, race/ethnicity, presence of diabetes mellitus, baseline comorbid conditions, history of tobacco smoking, dialysis vintage categories, primary insurance, marital status, residual renal function, dialysis dose as indicated by single pool Kt/V, serum intact parathyroid hormone and calcium concentrations.

Figure 3

Association between time-averaged serum phosphorus levels and all-cause mortality using Cox proportional hazard models in patients aged 15-<45 years (A), 45-<65 years (B), 65-<70 years (C), 70-<75 years (D) and ≥75 years (E). Case-mix model was adjusted for age, gender, race/ethnicity, presence of diabetes mellitus, baseline comorbidities, history of tobacco smoking, dialysis vintage categories, primary insurance, marital status, types of vascular access, dialysis dose as indicated by single pool Kt/V and residual renal function. Case-mix and MICS model was adjusted for all case-mix covariates plus body mass index, serum levels of albumin, total-iron binding capacity, ferritin, creatinine, calcium, intact parathyroid hormone, bicarbonate, hemoglobin, blood white blood cells, lymphocyte percentage and normalized protein nitrogen appearance. Abbreviation: MICS, malnutrition-inflammation complex syndrome.

Figure 4

Association between time-averaged serum phosphorus levels and cardiovascular mortality using Cox proportional hazard models in patients aged 15-<45 years (A), 45-<65 years (B), 65-<70 years (C), 70-<75 years (D) and ≥75 years (E). Case-mix model was adjusted for age, gender, race/ethnicity, presence of diabetes mellitus, baseline comorbidities, history of tobacco smoking, dialysis vintage categories, primary insurance, marital status, types of vascular access, dialysis dose as indicated by single pool Kt/V and residual renal function. Case-mix and MICS model was adjusted for all case-mix covariates plus body mass index, serum levels of albumin, total-iron binding capacity, ferritin, creatinine, calcium, intact parathyroid hormone, bicarbonate, hemoglobin, blood white blood cells, lymphocyte percentage and normalized protein nitrogen appearance. Abbreviation: MICS, malnutrition-inflammation complex syndrome.