Phosphate Balance and Outcome in Advanced CKD

Background: Perturbation of phosphate homeostasis portends unfavorable outcome in CKD. Although some lines of evidence suggest an association with mortality, serum levels of phosphate poorly reflect phosphate balance. A considerable effort is devoted to definine new markers of phosphate homeostasis. We investigated the association of fraction excretion of phosphate (FeP) with relevant outcome in advanced CKD. Methods: Retrospective, longitudinal study of 407 CKD subjects (age 66 years, 43% female, mean creatinine clearance 32 ml/min) receiving Nephrology care in Italy. Demographic and clinical characteristics were obtained at the time of referral. Routine laboratory and 24-urine collection were used. Risk of CKD progression to ESRD, all-cause mortality as well as the composite of the 2 were regarded as outcome of interest. ANOVA, logistic regression and survival analysis were used to compare patients’ characteristics across quartiles of FeP, detect predictors of FeP and the association of FeP with the outcome of interest. Results: Higher FeP was associated with older age, higher azotemia and PTH levels as well as lower creatinine clearance, serum phosphate and 24-h urine potassium excretion (all p-values<0.01). After adjustment for confounders, abnormal FeP (>20%) was inversely associated with creatinine clearance (B-0.03, p=0.006), diastolic blood pressure (B-0.04, p=0.01) and serum phosphate (B-0.43, p=0.008). Independent of multiple adjustments, a graded and independent association between quartiles of FeP and ESRD but not all-cause mortality was detected. Risk/quartile of FeP Low Mid-Low Mid-High High ESRD ref 3.28(0.87-12.3) 7.33(2.13-25.1) 12.3(3.64-41.7) Mortality ref 1.44(0.83-2.48) 1.68(0.98-2.88) 1.33(0.72-2.45) Composite ref 2.01(1.22-3.31) 2.29(1.41-3.70) 2.39(1.44-3.99) Conclusions: FeP is associated with ESRD but not all-cause mortality risk in a large cohort of advanced CKD patients. Future efforts are required to validate FeP as a marker of phosphate balance and if CKD progression explains the risk burden of phosphate imbalances in this high-risk population.