Calcium and the kidney--from stones to molecules.

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Shortly after the introduction of the thiazide diuretics it was noted that they lower the excretion of Ca2+ in the urine, enough so that they were introduced for the therapy of hypercalciuria in calcareous stone formers. This observation prompted us to begin a series of investigations designed to better understand the handling of Ca2+ by the kidney in general, and the effects of diuretics on Ca2+ transport in particular. Since it was already known that the excretion of Ca2+ followed closely the excretion of Na+ we postulated that the effects of diuretics are related to the shrinkage of extracellular (ECF) volume which signals the kidney to enhance filtrate absorption particularly in the proximal tubule. This we supported with studies showing that calcium excretion will return to the original elevated level, inspite of continued administration of the diuretic, if a high salt intake were allowed. We also showed the opposite, namely that hypercalciuria can be produced by mineralocorticoid administration if liberal salt intake were allowed, and is prevented by salt restriction. This latter observation antedated the clinical observation that primary aldosteronism is accompanied by hypercalciuria. These studies clearly showed the importance of ECF volume in determining urinary excretion of Ca2+. The site of action in the nephron of volume changes was thought to be the proximal convoluted tubule. Volume expansion had already been shown to depress proximal tubular absorption of Ca2+. We carried out studies using in situ micropuncture and demonstrated that ECF volume depletion caused by thiazide diuretics results in enhanced absorption in the proximal tubule confirming the suspicion that changes in ECF volume were translated into reciprocal changes in proximal tubular absorption. Meanwhile we showed that a different group of diuretics, the high-ceiling diuretics, unlike the thiazides produce a major increase in Ca2+ excretion suggesting that they exert their effects at a different site in the nephron, namely the loop of Henle. These and many other studies dictated that we examine more directly the handling of Ca2+ by the kidney, and for that purpose we employed the technic of in vitro microperfusion of isolated renal tubule segments. In the S2 segment of the proximal convoluted tubule we were able to show that Ca2+ absorption was entirely passive, following the electrochemical gradient for calcium present in this segment (luminal PD positive, tubular fluid [Ca2+] greater than plasma [Ca2+]).(ABSTRACT TRUNCATED AT 400 WORDS)

Original languageEnglish (US)
Pages (from-to)203-221
Number of pages19
JournalVerhandelingen - Koninklijke Academie voor Geneeskunde van Belgie
Issue number3
StatePublished - Jan 1 1990

ASJC Scopus subject areas

  • Medicine(all)


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