Research project on causal assessment of CKD-MBD biomarkers in CKD

Objectives:

• To assess the causal effect of longitudinal alterations in key CKD-MBD biomarkers (phosphate, calcium, and parathyroid hormone) on CKD progression in older adults with advanced CKD not yet on dialysis. Specifically, to evaluate the combined versus individual impact of these biomarker alterations on eGFR decline and the risk of dialysis initiation.
• To explore sex-related differences in the association between mineral disorders and CKD outcomes.
• To apply the parametric g-formula, a causal inference method, to account for time-varying confounding, informative censoring, and competing risks.

Results:

• Hyperphosphatemia and hyperparathyroidism, alone or combined, were associated with a faster decline in kidney function and a higher risk of dialysis initiation.
• The most adverse phenotype—hyperphosphatemia + hypocalcemia + hyperparathyroidism—was linked to a mean eGFR difference of −3.7 ml/min/1.73m² and a 75% higher dialysis risk after 3 years.
• Isolated hypercalcemia was not associated with CKD progression.
• The effect of mineral abnormalities on eGFR decline was similar between males and females, but the risk of dialysis appeared stronger in males.