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Chronic kidney disease (CKD) profoundly disturbs the delicate balance of calcium (Ca), phosphate (POâ‚„), vitamin D, and parathyroid hormone (PTH). As GFR declines, the kidneys fail to excrete phosphate and to activate vitamin D, leading to:
Abnormality | Mechanism | Consequence | Typical Stage |
---|---|---|---|
↓ Vitamin D Activation | ↓ 1α-hydroxylase → ↓ calcitriol (1,25-dihydroxyvitamin D) → ↓ intestinal Ca absorption | ↓ Serum Ca (hypocalcemia) | Begins CKD stage 3 (eGFR <60) |
↑ Phosphate Retention | ↓ Renal excretion → ↑ serum phosphate | Binds Ca → ↓ serum Ca Promotes vascular calcification | Early CKD (eGFR <60) |
Secondary Hyperparathyroidism | Low Ca + ↓ calcitriol chronically stimulate parathyroid glands | ↑ PTH → ↑ bone resorption → renal osteodystrophy | Typically CKD stage 3–5 |
↑ FGF-23 | Early rise to ↑ phosphate excretion | Suppresses 1α-hydroxylase → further ↓ calcitriol → worsens hypocalcemia | Early CKD (stages 2–3) |
Reduced Receptor Sensitivity | CKD milieu (↑ phosphate, uraemia) ↓ Ca-sensing and vitamin D receptor expression in parathyroid glands | ↓ Feedback sensitivity → further ↑ PTH | Advanced CKD |
Bone–Mineral Axis Dysregulation | Disruption of kidney–parathyroid–bone signalling | CKD-MBD: high-turnover bone disease (osteitis fibrosa) or low-turnover (adynamic bone disease) | CKD stages 3–5 |
Chronic kidney disease (CKD) sets up a “perfect storm” for mineral imbalance:
↑ Phosphate retention and...
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