Renal and systemic acid-base effects of the chronic administration of hypercalcemia-producing agents: Calcitriol, PTH, and intravenous calcium

Hulter, Henry N.; Sebastián, Anthony; Toto, Robert D.; Bonner, E. L.; Ilnicki, L

doi:10.1038/ki.1982.45

Cited by 35 publications

(21 citation statements)

References 32 publications

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“…In previous studies, PTH administration has been shown to generate a metabolic alkalosis (15)(16)(17). Moreover, hypercalcemia independent of PTH has also been reported to generate a metabolic alkalosis (6,21).…”

Section: Discussionmentioning

confidence: 99%

“…In 1970, Wills (26) suggested that PTH-induced bone resorption mobilized phosphate to act as a buffer to neutralize acidosis. In subsequent studies, PTH administration has been shown to increase net acid excretion (14,24) and induce metabolic alkalosis in dogs and humans by both renal and extrarenal mechanisms (15)(16)(17). Because PTH appears to have a role in acid-base homeostasis, it would seem reasonable that acid-base disorders may affect PTH secretion.…”

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confidence: 99%

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Role of acidosis-induced increases in calcium on PTH secretion in acute metabolic and respiratory acidosis in the dog

López¹,

Aguilera–Tejero²,

Estepa³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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of acidosis-induced increases in calcium on PTH secretion in acute metabolic and respiratory acidosis in the dog. Am J Physiol Endocrinol Metab 286: E780 -E785, 2004. First published January 13, 2004 10.1152/ajpendo.00473.2003.-Recently, we showed that both acute metabolic acidosis and respiratory acidosis stimulate parathyroid hormone (PTH) secretion in the dog. To evaluate the specific effect of acidosis, ionized calcium (iCa) was clamped at a normal value. Because iCa values normally increase during acute acidosis, we now have studied the PTH response to acute metabolic and respiratory acidosis in dogs in which the iCa concentration was allowed to increase (nonclamped) compared with dogs with a normal iCa concentration (clamped). Five groups of dogs were studied: control, metabolic (clamped and nonclamped), and respiratory (clamped and nonclamped) acidosis. Metabolic (HCl infusion) and respiratory (hypoventilation) acidosis was progressively induced during 60 min. In the two clamped groups, iCa was maintained at a normal value with an EDTA infusion. Both metabolic and respiratory acidosis increased (P Ͻ 0.05) iCa values in nonclamped groups. In metabolic acidosis, the increase in iCa was progressive and greater (P Ͻ 0.05) than in respiratory acidosis, in which iCa increased by 0.04 mM and then remained constant despite further pH reductions. The increase in PTH values was greater (P Ͻ 0.05) in clamped than in nonclamped groups (metabolic and respiratory acidosis). In the nonclamped metabolic acidosis group, PTH values first increased and then decreased from peak values when iCa increased by Ͼ0.1 mM. In the nonclamped respiratory acidosis group, PTH values exceeded (P Ͻ 0.05) baseline values only after iCa values stopped increasing at a pH of 7.30. For the same increase in iCa in the nonclamped groups, PTH values increased more in metabolic acidosis. In conclusion, 1) both metabolic acidosis and respiratory acidosis stimulate PTH secretion; 2) the physiological increase in the iCa concentration during the induction of metabolic and respiratory acidosis reduces the magnitude of the PTH increase; 3) in metabolic acidosis, the increase in the iCa concentration can be of sufficient magnitude to reverse the increase in PTH values; and 4) for the same degree of acidosis-induced hypercalcemia, the increase in PTH values is greater in metabolic than in respiratory acidosis.hypercalcemia; metabolic acidosis; parathyroid hormone; respiratory acidosis BESIDES ITS WELL-KNOWN EFFECT on calcium homeostasis, parathyroid hormone (PTH) has also been associated with changes in the acid-base status. In 1970, Wills (26) suggested that PTH-induced bone resorption mobilized phosphate to act as a buffer to neutralize acidosis. In subsequent studies, PTH administration has been shown to increase net acid excretion (14, 24) and induce metabolic alkalosis in dogs and humans by both renal and extrarenal mechanisms (15-17). Because PTH appears to have a role in acid-base homeostasis, it would seem reasonable that acid-base disorders may...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Role of acidosis-induced increases in calcium on PTH secretion in acute metabolic and respiratory acidosis in the dog

López¹,

Aguilera–Tejero²,

Estepa³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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“…in our laboratory have demonstrated that chronic neutral phosphate administration in the rat, such as sodium and potassium salts, induces renal metabolic alkalosis secondary to sustained increased proton secretion in collecting ducts during up to 7 d (9). Finally, we have shown (10) that hypercalcemia per se increases the proximal and thus renal reabsorption of bicarbonate relative to chloride, which, if of sufficient magnitude and/or duration, would induce hyperbicarbonatemia and hypochloremia; this calcium effect on the proximal tubule may explain the chronic metabolic alkalosis, at least in part of renal origin, associated with hypercalcemia secondary to hyperparathyroidism or 1,25-dihydroxycholecalciferol administration (6,8), or observed in patients with various neoplasms (1 1).…”

Section: Introductionmentioning

confidence: 98%

“…They had been fed a standard commercial chow (A 04; UAR, Villemoisson-sur-Orge, France) containing 5.9 g/kg phosphorus, 6.0 g/kg calcium, and 2,020 IU/kg vitamin D3 for at least 7 d before the study. Food was withheld [14][15][16] h before the experiment, but all animals had free access to water before anesthetization with Inactin (5-ethyl-5-[ I-methyl-propyl]-2-thiobarbituric acid), 100 mg/kg body wt.…”

Section: Methodsmentioning

confidence: 99%

Acute metabolic acidosis enhances circulating parathyroid hormone, which contributes to the renal response against acidosis in the rat.

Bichara¹,

Mercier²,

Borensztein³

et al. 1990

J. Clin. Invest.

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Acute PTH administration enhances final urine acidification in the rat. HCl was infused during 3 h in rats to determine the parathyroid and renal responses to acute metabolic acidosis. Serum immunoreactive PTH (iPTH) concentration significantly increased and nephrogenous adenosine 3',5'-cyclic monophosphate tended to increase during HCO loading in intact and adrenalectomized (ADX) rats despite significant increments in plasma ionized calcium. Strong linear relationships existed between serum iPTH concentration and arterial bicarbonate or proton concentration (P < 0.0001). Serum iPTH concentration and NcAMP remained stable in intact time-control rats and decreased in CaCl2-infused, nonacidotic animals. Urinary acidification was markedly reduced in parathyroidectomized (PTX) as compared with intact rats during both basal and acidosis states; human PTH-(1-34) infusion in PTX rats restored in a dose-dependent manner the ability of the kidney to acidify the urine and excrete net acid. Acidosis-induced increase in urinary net acid excretion was observed in intact, PTX, and ADX, but not in ADX-thyroparathyroidectomized rats.We conclude that (a) acute metabolic acidosis enhances circulating PTH activity, and (b) PTH markedly contributes to the renal response against acute metabolic acidosis by enhancing urinary acidification. (J. Clin. Invest. 1990. 86:430-443.)

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“…Localization of CaSR in A-type intercalated cells (ICs) in the cortical collecting duct (CCD) suggests a potential role of this receptor in regulation of proton secretion. Early studies demonstrated that acute hypercalcemia increases urine acid secretion (Richet et al 1963), while metabolic alkalosis observed in two models of hypercalcemia (PTH-and vitamin D-induced) most likely be caused by hypercalcemia, as PTH secretion differs in these two models (Hulter et al 1982;Mitnick et al 1982). If so, hypercalcemia-induced urine acidification is probably mediated via CaSR.…”

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confidence: 99%

Calcium-sensing Receptor Stimulates Luminal K+-dependent H+ Excretion in Medullary Thick Ascending Limbs of Henle's Loop of Mouse Kidney

Farajov

Morimoto

Aslanova

et al. 2008

Tohoku J. Exp. Med.

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The calcium-sensing receptor (CaSR) is known well as a sensor of extracellular calcium for regulating parathyroid hormone secretion. CaSR is located along all nephron segments in the kidney. While hypercalcemia strongly enhances urinary acidification, the relationship between CaSR and acid-base metabolism in the kidney is still uncertain. In the present study, we examined whether CaSR activation caused acid secretion in the medullary thick ascending limb (mTAL), which is one of the major nephron segments involved in both mineral and acid-base regulation. The effects of a potent calcimimetic neomycin (Neo) on intracellular pH (pHi) were analyzed in the in vitro miroperfused mouse mTALs. The mTALs were incubated with 2,7-bis-(2-carboxyethyl)-5(6)-carboxyfluoresceine-acetoxymethylester (BCECF-AM) for microfluorescent pHi measurements. In HCO 3 -/CO 2 -buffered solution, the steady-state pHi was 7.17 ± 0.01 (n = 19). Basolateral Neo at 0.4 mM in basolateral side significantly alkalinized the mTAL cells to 7.28 ± 0.02 (n = 19), while Neo in the lumen had no effect on pHi. Neo in the basolateral side alkalinized the mTALs in the absence of ambient Na + and the presence of H + -ATPase inhibitor bafilomycin in the lumen, indicating that the effect of Neo is unrelated to Na + -dependent acid-base transporters such as Na

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Renal and systemic acid-base effects of the chronic administration of hypercalcemia-producing agents: Calcitriol, PTH, and intravenous calcium

Cited by 35 publications

References 32 publications

Role of acidosis-induced increases in calcium on PTH secretion in acute metabolic and respiratory acidosis in the dog

Role of acidosis-induced increases in calcium on PTH secretion in acute metabolic and respiratory acidosis in the dog

Acute metabolic acidosis enhances circulating parathyroid hormone, which contributes to the renal response against acidosis in the rat.

Calcium-sensing Receptor Stimulates Luminal K+-dependent H+ Excretion in Medullary Thick Ascending Limbs of Henle's Loop of Mouse Kidney

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