Parathyroid hormone (PTH) binds the PTH1 receptor (PTH1R), a Gs- and Gq-coupled GPCR. In chronic kidney disease (CKD), secondary hyperparathyroidism develops. The initial biochemical trigger in CKD that drives increased PTH secretion is:
- A Hyperphosphatemia directly activating PTH gene transcription
- B Hypocalcemia from reduced calcitriol synthesis and hyperphosphatemia causing CaSR activation ✓
- C Reduced FGF-23 production from bone causing increased PTH
- D Increased 1-alpha-hydroxylase activity in remnant nephrons causing hypervitaminosis D
Explanation
In CKD, reduced functional nephron mass reduces 1-alpha-hydroxylase activity, decreasing calcitriol (1,25-OH2-D3) synthesis. Reduced calcitriol causes: (1) impaired intestinal calcium absorption leading to hypocalcemia, and (2) reduced calcitriol-mediated suppression of PTH gene transcription in the parathyroid. Simultaneously, reduced GFR causes phosphate retention and hyperphosphatemia; excess phosphate precipitates calcium, worsening hypocalcemia, and phosphate directly (via reduced FGF-23 or Pit2 receptor) also stimulates PTH secretion. The calcium-sensing receptor (CaSR) on parathyroid cells detects low Ca2+ and releases its inhibition of PTH secretion. FGF-23 from osteocytes normally inhibits 1-alpha-hydroxylase and PTH; it is actually elevated in CKD (a compensatory response).
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.