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.

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Title:	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.
Alternate Title:	El aumento de la concentració n de fosfato sérico dentro de los niveles de referencia normales se asocia con la mortalidad por todas las causas en pacientes con ERC sin diálisis: un estudio de cohorte prospectivo de cinco años.
Authors:	Cerqueira, Ana^1,2,3 ana.cerqueira@ulssjoao.min-saude.pt, Quelhas-Santos, Janete^2,3, Paulo, Núria¹, Dias, Claúdia Camila^2,3, Pestana, Manuel^1,2,3
Source:	Nefrologia. Nov2025, Vol. 45 Issue 9, p1-7. 7p.
Subjects:	MORTALITY, PHOSPHATES, MORTALITY risk factors, CARDIOVASCULAR diseases risk factors, CHRONIC kidney failure, FIBROBLAST growth factors, HEMODIALYSIS, COHORT analysis
Abstract (English):	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/1.73 m² (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 (<3 mg/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. [ABSTRACT FROM AUTHOR]
Abstract (Spanish):	Introducció n y objetivos: La morbilidad y mortalidad cardiovascular (CV) están marcadamente aumentadas en pacientes con enfermedad renal crónica (ERC) no sometidos a diálisis. Por lo tanto, el manejo preciso de los factores de riesgo CV involucrados en la ERC es crucial para mejorar los resultados. Los niveles de fosfato sérico (Pi) y FGF-23 se han relacionado con un mayor riesgo de eventos CV en la ERC. Sin embargo, los umbrales exactos de Pi y FGF-23, a partir de los cuales aumenta el riesgo de eventos adversos, siguen siendo desconocidos. Material y métodos: Evaluamos la expresió n de FGF-23 intacto (iFGF-23) y Pi en una població n de pacientes con ERC no sometidos a diálisis (n=82; 42 hombres, 40 mujeres; edad mediana de 61 años) e investigamos su asociació n con los resultados CV y renales durante un período de seguimiento de cinco años. Resultados: Al inicio, la tasa de filtració n glomerular estimada (eGFR), el iFGF-23 y el Pi medianos fueron de 45 ml/min/1.73m² (IQR 26.6-73.1), 69.9 μg/ml (IQR 33-117) y 3.4 mg/dL (IQR 3.3-3.9), respectivamente. El análisis univariante mostró una fuerte asociació n de tanto iFGF-23 como Pi con la edad, el índice de comorbilidad de Charlson, la hipertensió n y la diabetes. Además, tanto el iFGF-23 como el Pi se asociaron con el resultado compuesto (eventos CV y cerebrovasculares mayores - MACCEs, hospitalizaciones y mortalidad por todas las causas) durante el seguimiento. Asimismo, el Pi se asoció de manera independiente con la mortalidad por todas las causas durante el seguimiento. La segmentació n de la població n en terciles, según los niveles de Pi (<3 mg/dL; 3-3.6 mg/dL; ≥3.7 mg/dL) dentro de los niveles séricos de referencia, mostró una distribució n de la mortalidad de 0%, 20% y 80% (p=0.034), respectivamente. Conclusiones: Nuestros resultados refuerzan la asociació n de tanto iFGF-23 como Pi con resultados CV compuestos en pacientes con ERC no sometidos a diálisis y sugieren además que el Pi, dentro de los niveles de referencia actuales, puede comportarse como un factor de riesgo independiente de mortalidad en esta població n. Se sugiere que una reevaluació n de los niveles de referencia de Pi para una intervenció n terapéutica temprana en esta població n podría estar justificada. [ABSTRACT FROM AUTHOR]
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Database:	MedicLatina

Description
Abstract:	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/1.73 m² (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 (<3 mg/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. [ABSTRACT FROM AUTHOR]
ISSN:	02116995
DOI:	10.1016/j.nefro.2025.501352