A 67-year-old man was found to have a plasma calcium level of 12.2 mg/dL during a follow-up visit. The man had a 3-year history
of Hodgkin lymphoma. He was recently diagnosed with nephrolithiasis for which he had been treated with hydrochlorothiazide forthe past 3 weeks. Which of the following best explains the most likely mechanism of thiazideinduced hypercalcemia? a. Activation of the Na+/Ca2+ exchanger in the distal tubule
b. Increased Ca2+ reabsorption in the proximal tubule
c. Decreased secretion of parathyroid hormone
d. Decreased renal excretion of vitamin D
e. Activation of Na+/K+/2Cl− symporter in the thick ascending loop of Henle
f. Increased glomerular filtration of Ca2+
Activation of the Na+/Ca2+ exchanger in the distal tubule is the most likely mechanism of thiazide hypercalcemia
Thiazide-hypercalcemia is a well-known clinical condition. By inhibiting the thiazide-sensitive NaCl transporter in the distal convoluted tubule, which is closely related to calcium transport, thiazides cause an increase in sodium excretion.
Thiazides hypercalcemia decreases urine calcium levels while raising blood calcium levels via promoting calcium reabsorption from the luminal membrane into the interstitium in exchange for sodium. High calcium levels are a well-known adverse effect of thiazide hypercalcemia diuretics including hydrochlorothiazide (Microzide) and chlorthalidone, which are used to treat high blood pressure. By blocking calcium from being discharged in the urine, which can also result in kidney stones, these drugs can boost calcium levels.
