A patient with chronic kidney disease stage 4 develops secondary hyperparathyroidism. Which sequence of events correctly describes the pathogenesis?

• A Reduced GFR → phosphate retention → hyperphosphatemia → direct FGF23 suppression → reduced 1,25-dihydroxyvitamin D → hypocalcemia → PTH secretion stimulated
• B Reduced renal 1α-hydroxylase activity → decreased 1,25-(OH)2D3 → reduced intestinal Ca2+ absorption → hypocalcemia → PTH secretion; additionally, phosphate retention develops ✓
• C Increased PTH directly causes renal failure by promoting nephrocalcinosis
• D CKD causes primary hyperparathyroidism due to adenoma formation under uremic conditions

Explanation

In CKD, multiple mechanisms drive secondary hyperparathyroidism: (1) reduced functional renal mass decreases 1α-hydroxylase → less 1,25-(OH)2D3 (calcitriol) → impaired intestinal Ca2+ and phosphate absorption → hypocalcemia → increased PTH. (2) Phosphate retention (reduced GFR) → hyperphosphatemia → forms insoluble calcium-phosphate complexes → hypocalcemia → further PTH stimulation. (3) FGF23 (elevated early in CKD) suppresses 1α-hydroxylase, worsening calcitriol deficiency. (4) Uremia reduces CaSR sensitivity on parathyroid cells. All these converge to cause the elevated PTH of secondary hyperparathyroidism.

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

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