Current Controversies on Adequate Circulating Vitamin D Levels in CKD

Area of Science:

• Endocrinology
• Nephrology
• Mineral Metabolism

Background:

• Secondary hyperparathyroidism (SHPT) management in chronic kidney disease (CKD) has evolved significantly over 50 years.
• Understanding of the vitamin D endocrine system's role in CKD progression has been reshaped by key discoveries.
• Three critical paradigm shifts have altered the approach to SHPT in CKD.

Purpose of the Study:

• To synthesize pathophysiological insights and clinical evidence underlying major shifts in SHPT management in CKD.
• To review the evolution from calcitriol replacement to selective vitamin D receptor activators (VDRAs).
• To discuss the impact of nutritional vitamin D deficiency and the FGF23-Klotho axis on CKD pathophysiology and treatment.

Main Methods:

• Review of key pathophysiological insights in SHPT and CKD.
• Synthesis of clinical evidence related to vitamin D therapy and the FGF23-Klotho axis.
• Analysis of the therapeutic dilemmas posed by current treatment strategies.

Main Results:

• Selective vitamin D receptor activators (VDRAs) offer survival benefits beyond mineral metabolism.
• Nutritional vitamin D deficiency is prevalent in CKD, posing mortality risks, but optimal management is controversial.
• The FGF23-Klotho axis presents a therapeutic dilemma: VDRAs increase FGF23, while calcimimetics do not improve Klotho.

Conclusions:

• SHPT management in CKD is complex, involving intricate interactions beyond PTH control.
• Nuanced therapeutic strategies are needed to balance FGF23 burden and Klotho preservation.
• Overcoming diagnostic limitations in monitoring the FGF23-Klotho axis is crucial for personalized therapy and improved CKD outcomes.