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1-Alpha-Hydroxylase Deficiency CKD Persistent PTH — ESENeph MCQ

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ModerateChronic Kidney Disease1-Alpha-Hydroxylase Deficiency CKD Persistent PTHESENeph

A 40-year-old man with CKD G3b develops secondary hyperparathyroidism (PTH 25 pmol/L). He is started on Cholecalciferol to replete his vitamin D (25-OH D 18 nmol/L). After 3 months, his 25-OH D is 85 nmol/L but PTH has only fallen to 20 pmol/L. His calcium is 2.2 and phosphate 1.5. What explains the persistent PTH elevation despite vitamin D repletion?

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Correct answer: B — In CKD G3b-G4, the kidney has reduced 1-alpha-hydroxylase activity – even with adequate 25-OH D substrate, conversion to active 1,25-dihydroxyvitamin D is impaired; this explains persistent PTH elevation despite replete native vitamin D; the next step is active vitamin D (Alfacalcidol/Calcitriol)

This scenario illustrates the pathophysiology of CKD-MBD: in CKD G3b-G5, progressive nephron loss reduces the mass of proximal tubular cells containing 1-alpha-hydroxylase, the enzyme that converts 25-OH vitamin D to its active form (1,25-dihydroxyvitamin D). Even with replete substrate (25-OH D 85 nmol/L), active vitamin D production is insufficient to suppress PTH. Additionally, elevated FGF23 in CKD directly suppresses 1-alpha-hydroxylase. The treatment ladder is: replete native vitamin D first, then add active vitamin D (Alfacalcidol/Calcitriol) if PTH remains elevated with replete stores.

Reference: KDIGO 2017 – CKD-MBD; NICE – CKD-MBD Pathway