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The primary hormone responsible for maintaining calcium (Ca++) balance in the body is PTH. It exerts the most powerful control on renal Ca++ excretion by stimulating Ca++ reabsorption by the kidneys. PTH reduces Ca++ excretion by inhibiting the reabsorption of NaCl and fluid in the proximal tubule. However, it stimulates Ca++ reabsorption in the TAL of the loop of Henle and the distal tubule. Overall, PTH enhances renal Ca++ reabsorption. Changes in plasma [Ca++] levels also influence urinary Ca++ excretion. Hypercalcemia increases excretion while hypocalcemia decreases it. Hypercalcemia achieves this by reducing proximal tubule Ca++ reabsorption, inhibiting Ca++ reabsorption in the TAL of the loop of Henle through the CaSR activation, and suppressing Ca++ reabsorption in the distal tubule by reducing PTH levels. As a result, urinary Ca++ excretion increases. Conversely, hypocalcemia increases Ca++ reabsorption in the proximal tubule and TAL, leading to decreased urinary Ca++ excretion. While calcitriol enhances Ca++ reabsorption in the distal tubule, it is not as effective as PTH.

Several factors can disrupt Ca++ excretion. An increase in plasma [Pi] concentration, caused by a sudden increase in dietary Pi intake or reduced kidney function, elevates PTH levels and decreases Ca++ excretion by lowering ionized plasma [Ca++] levels. A decline in plasma [Pi], due to dietary Pi depletion, has the opposite effect. Changes in extracellular fluid volume (ECFV) mainly affect Ca++ excretion by influencing NaCl and fluid reabsorption in the proximal tubule. Volume contraction increases Ca++ reabsorption by enhancing NaCl and water reabsorption in the proximal tubule, resulting in decreased urinary Ca++ excretion. On the other hand, volume expansion has the opposite effect. Acidemia increases Ca++ excretion, while alkalemia decreases it. The regulation of Ca++ reabsorption by pH primarily occurs in the distal tubule. Alkalosis stimulates the apical membrane Ca++ channel (TRPV5), leading to increased Ca++ reabsorption. Acidosis, on the other hand, inhibits the same channel, reducing Ca++ reabsorption. Additionally, loop diuretics inhibit Ca++ reabsorption in the TAL, while thiazide diuretics stimulate Ca++ reabsorption in the distal tubule.

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Table 36.2 ). Of these, PTH exerts the most powerful control on renal Ca++ excretion; it is the primary hormone/ factor responsible for maintaining Ca++ homeostasis. Overall this hormone stimulates Ca++ reabsorption by the kidneys (i.e., reduces Ca++ excretion). Although PTH inhibits reabsorption of NaCl and fluid, and therefore Ca++ reabsorption by the proximal tubule, PTH stimulates Ca++ reabsorption by the TAL of the loop of Henle and the distal tubule. Thus the net effect of PTH is to enhance renal Ca++ reabsorption. Changes in plasma [Ca++] also regulate urinary Ca++ excretion, with hypercalcemia increasing excretion and hypocalcemia decreasing excretion. Hypercalcemia increases urinary Ca++ excretion by: (1) reducing proximal tubule Ca++ reabsorption (reduced paracellular reabsorption due to increased interstitial fluid [Ca++]); (2) inhibiting Ca++ reabsorption by the TAL of the loop of Henle via activation of the CaSR located in the basolateral membrane of these cells (NaCl reabsorption is decreased, thereby reducing the magnitude of the lumen-positive Vte); and (3) suppressing Ca++ reabsorption by the distal tubule by reducing PTH levels. As a result, urinary Ca++ excretion increases. Hypocalcemia has the opposite effect on urinary Ca++ excretion, primarily by increasing Ca++ reabsorption by the proximal tubule and TAL. Calcitriol enhances Ca++ reabsorption by the distal tubule, but it is less effective than PTH.
Several factors disturb Ca++ excretion. An increase in plasma [Pi] concentration (e.g., caused by a dramatic increase in dietary intake of Pi or by reduced kidney function) elevates PTH levels both directly and by decreasing the ionized plasma [Ca++] and thereby decreases Ca++ excretion. A decline in plasma [Pi] (e.g., caused by dietary Pi depletion) has the opposite effect (NOTE: with normal kidney function, changes in dietary Pi intake over a sevenfold range has no effect on plasma [Pi]). Changes in ECFV alter Ca++ excretion mainly by affecting NaCl and fluid reabsorption in the proximal tubule. Volume contraction increases NaCl and water reabsorption by the proximal tubule and thereby enhances Ca++ reabsorption. Accordingly, urinary Ca++ excretion declines. Volume expansion has the opposite effect. Acidemia increases Ca++ excretion, whereas alkalemia decreases excretion. Regulation of Ca++ reabsorption by pH
CHAPTER 36 Potassium, Calcium, and Phosphate Homeostasis aPTH inhibits Ca++ reabsorption by the proximal tubule but stimulates reabsorption by the TAL and distal tubule. Overall the net effect is to increase Ca++ reabsorption and thereby reduce urinary Ca++ excretion. CaSR, calcium-sensing receptor. Modified from Mount DB, Yu A. Transport of inorganic solutes: sodium, chloride, potassium, magnesium, calcium and phosphate. In: Brenner BM (ed). Brenner and Rector’s The Kidney. 8th ed. Philadelphia: Saunders; 2008.
occurs primarily in the distal tubule. Alkalosis stimulates the apical membrane Ca++ channel (TRPV5), thereby increasing Ca++ reabsorption. By contrast, acidosis inhibits the same channel, thereby reducing Ca++ reabsorption. Finally, as noted earlier, loop diuretics inhibit Ca++ reabsorption by the TAL, and thiazide diuretics stimulate Ca++ reabsorption by the distal tubule.