Vitamin D calcium and phosphorus homeostasis

Vitamin D is converted to its active form 1,25-dihydroxyvitamin D by hydroxylation in the kidney, stimulating bone, intestine, and kidney to raise calcium and phosphorus levels. Hypophosphatemia, elevated PTH output, and low 1,25-dihydroxyvitamin D levels increase vitamin D production, while the opposite effects decrease its synthesis. Progressive loss of renal tissue impairs the kidney's ability to generate activated vitamin D.

The kidney plays a major role in calcium homeostasis, housing the hydroxylase enzyme which activates vitamin D. Furthermore, PTH directly enhances distal nephron calcium reabsorption. Roughly 60 per cent of the plasma calcium is filterable; the remainder is bound to albumin. Approximately 98 per cent of filtered calcium is reabsorbed and parallels sodium reabsorption in nephron segments up to the distal convoluted tubule. Loop diuretics promote calciuria by inhibiting sodium and calcium transport in the thick ascending loop of Henle, whereas thiazide diuretics, acting at the distal convoluted tubule, induce natriuresis and hypocalciuria. Finally, acidosis and alkalosis decrease and increase calcium binding respectively. Hence the metabolic acidosis of renal failure may increase ionized calcium levels while total serum calcium remains unchanged.

Several factors, namely dietary phosphorus load and PTH, influence renal regulation of serum phosphorus. An estimated 90 to 95 per cent of phosphorus is filterable; the remainder is protein bound. Roughly 5 to 20 per cent of filtered phosphorus is normally excreted. Increases in PTH levels and phosphorus intake hinder phosphorus reabsorption and promote phosphorus excretion. Other factors, such as extracellular fluid volume expansion, calcitonin, glucocorticoids, metabolic acidosis or alkalosis, and glucagon, induce hyperphosphaturia, whereas 1,25-dihydroxyvitamin D, insulin, growth hormone, and respiratory acidosis generate hypophosphaturia. Phosphorus retention typically occurs when the glomerular filtration rate falls below 25 ml/min.

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