No independent association of serum phosphorus with risk for death or progression to end-stage renal disease in a large screen for chronic kidney disease

Abstract

Whether higher serum phosphorus levels are associated with a higher risk for death and/or progression of chronic kidney disease (CKD) is not well established, and whether the association is confounded by access and barriers to care is unknown. To answer these questions, data of 10,672 individuals identified to have CKD (estimated glomerular filtration rate <60 ml/min per 1.73 m(2)) from those participating in a community-based screening program were analyzed. Over a median follow-up of 2.3 years, there was no association between quartiles of serum phosphorus and all-cause mortality (adjusted hazards ratio for serum phosphorus over 3.3 to 3.7, over 3.7 to 4.1, and over 4.1 mg/dl, respectively: 1.22 (0.95-1.56), 1.00 (0.76-1.32), and 1.00 (0.75-1.33); reference, serum phosphorus of 3.3 mg/dl and below). Individuals in the highest quartile for serum phosphorus had a significantly higher risk for progression to end-stage renal disease (ESRD) (unadjusted hazards ratio, 6.72 (4.16-10.85)); however, the risk became nonsignificant on adjustment for potential confounders. There was no appreciable change in hazards ratio with inclusion of variables related to access and barriers to care. Additional analyses in subgroups based on 12 different variables yielded similar negative associations. Thus, in the largest cohort of individuals with early-stage CKD to date, we could not validate an independent association of serum phosphorus with risk for death or progression to ESRD.

Figure 1

Kaplan–Meier survival analysis of time to death in individuals identified to have chronic kidney disease by quartiles of baseline serum phosphorus (Phos).

Figure 2. Forest plot showing hazards ratio with 95% confidence interval for the association between quartiles of serum phosphorus and all-cause mortality in subgroups based on 12 variables and in the entire study population

The range of serum phosphorus for each of the four quartiles were: quartile 1, <3.3 mg/dl (reference); quartile 2, >3.3 to 3.7 mg/dl; quartile 3, >3.7 to 4.1 mg/dl; and quartile 4, >4.1 mg/dl. All analyses are adjusted for the following covariates (except for the variable used to define the subgroup in each case): age, gender, race/ethnicity, year of screening, diabetes, hypertension, dyslipidemia, current tobacco use, body mass index, estimated glomerular filtration rate (eGFR), albuminuria, plasma glucose, calcium, parathyroid hormone, hemoglobin, chronic kidney disease (CKD) awareness, and health insurance.

Figure 3

Kaplan–Meier survival analysis of time to end-stage renal disease (ESRD) in individuals identified to have chronic kidney disease by quartiles of baseline serum phosphorus (Phos).

Figure 4. Forest plot showing hazards ratio with 95% confidence interval for the association between quartiles of serum phosphorus and progression to end-stage renal disease (ESRD) in subgroups based on 12 variables and in the entire study population

The range of serum phosphorus for each of the four quartiles were: quartile 1, <3.3 mg/dl (reference); quartile 2, >3.3 to 3.7 mg/dl; quartile 3, >3.7 to 4.1 mg/dl; and quartile 4, >4.1 mg/dl. All analyses are adjusted for the following covariates (except for the variable used to define the subgroup in each case): age, gender, race/ethnicity, year of screening, diabetes, hypertension, dyslipidemia, current tobacco use, body mass index, estimated glomerular filtration rate (eGFR), albuminuria, plasma glucose, calcium, parathyroid hormone, hemoglobin, chronic kidney disease (CKD) awareness, and health insurance. Please note that there was only one event of end-stage renal disease in individuals with albumin–creatinine ratio of <30 in quartile 3 of serum phosphorus.

Figure 5

Kaplan–Meier survival analysis of time to death or end-stage renal disease (ESRD) in individuals identified to have chronic kidney disease by quartiles of baseline serum phosphorus (Phos).