A patient with end-stage renal disease develops secondary hyperparathyroidism. The sequence of events leading to elevated PTH in CKD is:

• A Low 25-hydroxyvitamin D → reduced intestinal Ca absorption → hypocalcaemia → ↑PTH
• B Hypophosphataemia from renal phosphate wasting stimulating PTH
• C FGF-23 deficiency causing calcium-phosphate product elevation
• D Reduced 1,25-dihydroxyvitamin D (calcitriol) AND hyperphosphataemia → hypocalcaemia → ↑PTH with reduced calcitriol further reducing PTH suppression ✓

Explanation

In CKD, reduced functional renal mass decreases 1-alpha-hydroxylase activity, reducing calcitriol synthesis. This impairs intestinal Ca absorption, causing hypocalcaemia, which stimulates PTH. Simultaneously, reduced GFR causes phosphate retention (hyperphosphataemia), which directly stimulates PTH and inhibits 1-alpha-hydroxylase further. Low calcitriol also reduces its direct inhibitory effect on PTH gene transcription. FGF-23 actually rises early in CKD (from osteocytes) to promote phosphaturia, but this itself inhibits 1-alpha-hydroxylase, compounding the calcitriol deficiency.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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