Increased serum phosphate concentration within the normal reference levels is associated with all-cause mortality in non-dialysis CKD patients: A five-year prospective cohort study

Introduction and objectives: Cardiovascular (CV) morbidity and mortality are markedly increased in non-dialysis patients with chronic kidney disease (CKD). Thus, the precise management of CV risk factors involved in CKD is crucial to improving outcomes. Serum phosphate (Pi) and FGF-23 levels have been linked with a higher risk of CV events in CKD. However, the exact thresholds of Pi and FGF-23, at which the risk of adverse events increases remain unknown. Materials and methods: We evaluated the expression of intact FGF-23 (iFGF-23) and Pi in a non-dialysis CKD patient population (n=82; 42M:40F; median age 61 years) and investigated their association with CV and renal outcomes, in a five-year follow-up period. Results: At baseline, the median estimated glomerular filtration rate (eGFR), iFGF-23, and Pi were 45 ml/min/1.73m 2 (IQ 26.6-73.1), 69.9 µg/ml (IQ 33-117) and 3.4 mg/dL (IQ 3.3-3.9), respectively. Univariate analysis showed a strong association of both iFGF-23 and Pi with age, Charlson Comorbidity Index, hypertension, and diabetes. In addition, iFGF-23 and Pi were both associated with the composite outcome (major CV and cerebrovascular events – MACCEs, hospitalizations, and all-cause mortality) during follow-up. Moreover, Pi was independently associated with all-cause mortality during follow-up. The segmentation of the population in terciles, according to Pi (<3mg/dL; 3-3.6 mg/dL; ≥3.7 mg/dL) within reference serum levels, showed a distribution of the fatality of 0%, 20% and 80% (p =0.034), respectively. Conclusions: Our results reinforce the association of both iFGF-23 and Pi with composite CV outcomes in non-dialysis CKD patients and further suggest that Pi, within current reference levels, may behave as an independent risk factor for mortality in this population. It is suggested that reassessing Pi reference levels for early therapeutic intervention in this population may be justified