Abstract
PurposeWhether higher serum phosphorus levels increase risk for kidney disease onset and progression to end-stage renal disease in those with normal renal function is largely unknown. We sought to determine whether higher serum phosphorus levels increase risk for end-stage renal disease within a large ethnically diverse population with normal kidney function. MethodsA retrospective longitudinal cohort study was performed in the period January 1, 1998 through December 31, 2008 of adults within a vertically integrated health plan (3.4 million members). The primary objective was to determine risk of incident end-stage renal disease. Baseline and time-averaged phosphorus were used for Cox regressions analyses to calculate hazard ratios (HR) adjusting for age, sex, race, pre-existing hypertension, and diabetes. ResultsA total of 94,989 subjects were identified in the 11-year observation period. Mean age of the cohort was 50 years, with 61% female, 38% white, 14% black, and 25% Hispanic. Population-based phosphorus quartile ranges were 1.9-3.0 mg/dL, 3.1-3.4 mg/dL, 3.5-3.8 mg/dL, and 3.9-5.7 mg/dL. End-stage renal disease occurred in 130 (0.1%) subjects. Every 0.5-mg/dL phosphorus increase demonstrated an adjusted HR of 1.40 (95% confidence interval [CI], 1.06-1.84) and HR for mortality of 1.09 (95% CI, 1.06-1.13). Adjusted HRs were 0.64 (95% CI, 0.37-1.11), 0.83 (95% CI, 0.50-1.39), and 1.48 (95% CI, 0.96-2.28) in the 2nd, 3rd, and 4th quartile, respectively, compared with the first phosphorus quartile. Time-averaged serum phosphorus demonstrated a similar relationship across quartiles and as a continuous variable. ConclusionIn our large, ethnically diverse cohort of non kidney disease subjects, higher serum phosphorus levels were associated with greater risk for end-stage renal disease and mortality.
Highlights
METHODSErized records, which included laboratory databases, disease registries, and electronic medical charts
Ethnically diverse population of nonchronic kidney disease subjects, we found a graded, independent association between higher serum phosphorus levels and risk of end-stage renal disease
Our study demonstrated a positive relationship between rising serum phosphorus and risk of end-stage renal disease, which may not have been as apparent when assessing this relationship using artificial phosphorus quartiles as we did in our analysis
Summary
Erized records, which included laboratory databases, disease registries, and electronic medical charts. The index time for survival analysis was function using estimated glomerular filtration rate (eGFR) This was calculated from the first available serum creatinine date of first serum phosphorus measurement. The causes of end-stage renal disease were identified where available using the Southern California Permanente Medical Group internal database, which is inclusive of all dialysis and renal transplant patients within Kaiser Permanente Southern California. Both baseline and time-averaged phosphorus levels were evaluated. Multivariable hazard ratios (HR) were calculated with adjustment for potential confounders including age, sex, race, and pre-existing hypertension and diabetes mellitus These same adjustments were made for time-averaged phosphorus and for analysis using phosphorus as a continuous variable. The study protocol was approved by the Kaiser Permanente Southern California Institutional Review Board with waiver of the need for informed consent
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