Effects of Normal Reference Range of Phosphorus and Corresponding PTH on Endothelial Function in CKD Patients

Area of Science:

• Nephrology
• Cardiovascular Medicine
• Endocrinology

Background:

• Endothelial dysfunction is prevalent in chronic kidney disease (CKD) and elevates cardiovascular disease (CVD) risk.
• Biomarkers of CKD-mineral bone disorder (CKD-MBD), including phosphorus, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23), are implicated in CKD-MBD pathogenesis and associated with endothelial dysfunction.
• The specific role of these biomarkers in inducing endothelial dysfunction in CKD patients with normal phosphorus levels requires further investigation.

Purpose of the Study:

• To investigate the association between CKD-MBD biomarkers (phosphorus, PTH, FGF23) and endothelial dysfunction in CKD patients with normal phosphorus levels.
• To determine if phosphorus and PTH levels independently predict endothelial dysfunction in this patient cohort.
• To explore the mediating effects of PTH on endothelial function.

Main Methods:

• Cross-sectional study involving 85 CKD patients with normal phosphorus levels, excluding those with estimated glomerular filtration rate (eGFR) <15 or on dialysis.
• Assessment of endothelial function using iontophoresis with laser doppler flowmetry (ILDF) and peripheral arterial tonometry (assessing reactive hyperemia index, RHI).
• Statistical analyses included Pearson's correlation, multiple regression, and mediation analyses to examine associations between CKD-MBD biomarkers and endothelial dysfunction.

Main Results:

• Endothelial dysfunction was detected in all subjects via ILDF and in 27% via RHI.
• Acetylcholine (Ach)-induced ILDF was significantly associated with eGFR, intact parathyroid hormone (iPTH), and VCAM-1.
• Reactive hyperemia index (RHI) was significantly related to phosphorus levels and iPTH. After adjusting for eGFR, iPTH and VCAM-1 remained independent predictors for ILDF-measured endothelial dysfunction, while iPTH and phosphorus were independent predictors for RHI-measured endothelial dysfunction. Mediation analyses confirmed PTH's significant indirect effects on ILDF and RHI.

Conclusions:

• Serum phosphorus and iPTH levels are significantly associated with endothelial dysfunction in CKD patients, even when phosphorus levels are normal.
• These findings highlight the importance of monitoring phosphorus and PTH in CKD patients for cardiovascular risk assessment.
• Targeting these biomarkers may offer therapeutic potential for mitigating endothelial dysfunction and associated cardiovascular complications in CKD.