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Increased serum phosphate concentration within the normal reference levels is associated with all-cause mortality in
Ana Cerqueira1, Janete Quelhas-Santos2, Núria Paulo3
1Unidade Local de Saúde São João, Porto, Portugal; Faculdade de Medicina da Universidade do Porto, Porto, Portugal; RISE - Rede de Investigação em Saúde, Porto, Portugal.
Insights
In non-dialysis chronic kidney disease (CKD) patients, elevated serum phosphate (Pi) and FGF-23 are linked to cardiovascular events. This study suggests Pi, even within reference ranges, independently predicts mortality, warranting reassessment of current Pi levels.
Area of Science:
- Nephrology
- Cardiology
- Biochemistry
Background:
- Cardiovascular disease is a major concern in non-dialysis chronic kidney disease (CKD) patients.
- Managing cardiovascular (CV) risk factors is critical for improving outcomes in CKD.
- Serum phosphate (Pi) and FGF-23 levels are implicated in CV risk, but precise thresholds remain unclear.
Purpose of the Study:
- To evaluate the association of intact FGF-23 (iFGF-23) and Pi with CV and renal outcomes in non-dialysis CKD patients.
- To investigate the independent risk factors for adverse events in this population.
- To explore potential reassessment of Pi reference levels for early intervention.
Main Methods:
- A five-year follow-up study of 82 non-dialysis CKD patients.
- Evaluation of intact FGF-23 (iFGF-23) and serum phosphate (Pi) levels at baseline.
- Analysis of associations with composite CV outcomes, hospitalizations, and all-cause mortality.
Main Results:
- Both iFGF-23 and Pi correlated with age, comorbidities, hypertension, and diabetes.
- iFGF-23 and Pi were associated with composite CV outcomes and mortality.
- Serum phosphate (Pi) independently predicted all-cause mortality, with higher Pi terciles showing increased fatality rates (0%, 20%, 80%).
Conclusions:
- iFGF-23 and Pi are associated with adverse CV outcomes in non-dialysis CKD.
- Serum phosphate (Pi) may be an independent mortality risk factor within current reference levels.
- Revisiting Pi reference ranges for early therapeutic intervention in CKD patients is recommended.
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 45mL/min/1.73m2 (IQ 26.6-73.1), 69.9μg/mL (IQ 33-117) and 3.4mg/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; 3-3.6mg/dL; ≥3.7mg/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.
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