(C-022) Exploring the prognostic importance of serum phosphate levels and hyperphosphatemia on mortality and composite endpoints in non-dialysis CKD patients: a real-world evidence study

Background: Serum markers of disordered mineral metabolism, such as abnormal serum phosphate levels, are associated with adverse outcomes in dialysis patients; however, their role in non-dialysis chronic kidney disease (CKD) remains unclear.

Objectives: To investigate the prognostic importance of serum phosphate levels and hyperphosphatemia on mortality and composite endpoints in non-dialysis CKD patients.

Methods:

Design: A prospective cohort study.
Setting: A cohort of 360 non-dialysis CKD patients aged ≥18 years, enrolled at the renal clinic of a tertiary care public teaching hospital, and followed for over 12 months. Patients on dialysis, receiving renal replacement therapy (RRT), or with end-stage renal disease (ESRD) at the baseline were excluded.
Exposures: Serum phosphate levels categorized into quartiles (Q1 to Q4), and hyperphosphatemia defined as serum phosphate levels exceeding 4.5 mg/dL.
Main outcome measures: Mortality and composite renal endpoints, including dialysis initiation, advancing to ESRD, and doubling of serum creatinine from the baseline.
Statistical analysis: Survival analyses using Kaplan-Meier curves and the Log-rank test, along with Cox proportional hazards models, were conducted to evaluate the association of serum phosphate quartiles and hyperphosphatemia with mortality and composite endpoints in STATA. A p-value < 0.05 was deemed statistically significant.

Results: The incidence of mortality significantly increased across quartiles, with the highest rate observed in Q4 (26.4%). The incidence of composite endpoints also rose significantly from 20.4% in Q1 to 64.4% in Q4. Dialysis initiation was most prevalent in Q4 (43.7%), and both ESRD progression and serum creatinine doubling exhibited similar upward trends.
Cox proportional hazards regression revealed a significant association between serum phosphate quartiles and mortality, with Q4 exhibiting over a threefold increased hazard of mortality (HR = 3.29, CI 95% 1.51-7.16, p=0.003) and composite endpoints (HR = 3.59, CI 95% 2.15-5.99, p< 0.005). When serum phosphate was modeled as a continuous variable, a 20% increased hazard of mortality (HR = 1.20, CI 95% 1.05-1.37, p=0.005) and a 20% increased hazard for composite endpoints (HR = 1.20, CI 95% 1.11-1.30, p< 0.005) were observed. Hyperphosphatemia was an independent predictor of both mortality (HR = 2.59, CI 95% 1.47-4.57, p=0.001) and composite endpoints (HR = 2.55, CI 95% 1.80-3.60, p< 0.005).

Conclusions: Elevated serum phosphate levels significantly increase the risk of mortality and composite endpoints in non-dialysis CKD patients. These findings underscore the importance of addressing phosphate levels as part of clinical management and risk stratification in non-dialysis CKD patients.