Mechanism of the Polyuria of Hypercalcemia

Goldfarb, Stanley; Agus, Zalman S.

doi:10.1159/000166780

Cited by 33 publications

(17 citation statements)

References 15 publications

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“…Consequently, metabolic acidosis in the TPTX model is to be expected. In the present study, it was also shown that the impairment in the concentrating ability was not corrected by calcium; as expected, both TPTX and TPTX+Ca 2+ groups developed hypercalciuria which could, per se, change the concentrating ability [18]. The influence of peritubular or intracellular Ca 2+ on the hydraulic permeability of the rabbit cortical collecting duct perfused in vitro was investigated by Jones et al [19].…”

Section: Discussionsupporting

confidence: 63%

Influence of Parathyroidectomy and Calcium on Rat Renal Function

Gil¹,

Gomes²,

Cavanal³

et al. 1999

Nephron

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Parathyroid hormone (PTH) has multiple effects on water and electrolyte transport along the nephron. However, the influences of PTH and calcium on the urinary concentration ability are not fully understood. In this study, clearance and microperfusion studies were performed in thyroparathyroidectomized (TPTX) rats either supplemented (TPTX+Ca²⁺) or not with calcium added to the ingested food as CaCl₂ (1.6 g/100 g). Acid-base data and renal functional parameters were measured in TPTX and TPTX+Ca²⁺ rats. Additional studies were performed in the isolated inner medullary collecting tubules of intact and TPTX rats to evaluate the osmotic permeability of this segment in the presence of 10^–6M PTH added to the bath. In these experiments the possible influence of PTH on antidiuretic hormone induced changes of the osmotic permeability in TPTX and TPTX+Ca²⁺ rats was also investigated. In the TPTX+Ca⁺ group, the glomerular filtration rate increased significantly when compared to the TPTX group (6.04 ± 0.42 vs. 4.88 ± 0.20 ml·min^–1·kg^–1; p < 0.05), but the U/P inulin ratio remained lower than control values (30.8 ± 1.48 vs. 54.0 ± 3.5; p < 0.05), which suggests that normal levels of PTH are necessary to maintain the concentrating ability. In a group of TPTX rats, an acute infusion of PTH (0.5 µg·min^–1·kg^–1) significantly decreased the urinary flow and increased the renal plasma flow, results that agree with the vasomodulator action of this hormone on the renal vasculature. A significant increase in the fractional K⁺ excretion observed in the TPTX+Ca²⁺ group as compared with both control and TPTX, groups suggests that the excreted load of Ca²⁺ may interfere with tubular K⁺ handling in the absence of PTH. PTH (10^–6M) added to the bath of the isolated inner medullary collecting tubules did not change the osmotic permeability, of intact, TPTX, and TPTX+Ca²⁺ rats. Furthermore, it did not modify the antidiuretic hormone induced changes in the osmotic permeability. These results suggest that this segment of the nephron is PTH insensitive as far as water and ion transport are concerned.

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Section: Discussionsupporting

confidence: 63%

Influence of Parathyroidectomy and Calcium on Rat Renal Function

Gil¹,

Gomes²,

Cavanal³

et al. 1999

Nephron

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“…Vasopressin regulates the countercurrent multiplication system and is modulated by increases in cAMP and PKC activity. Decreased responsiveness of the kidney to vasopressin appears to be an important cause of polyuria in hypercalcemia associated with changes in adenylate cyclase and PKC activities (4,11,25,34,45). Thus, CaR-mediated G q -and G i -coupled signaling that inhibits transporter function in a PGE 2 -dependent manner may counteract the effects of vasopressin in the mTAL, a mechanism that likely acts in concert with the CaR-mediated antagonism of AVP-dependent water permeability in the collecting duct (51).…”

Section: Discussionmentioning

confidence: 99%

Calcium-sensing receptor signaling pathways in medullary thick ascending limb cells mediate COX-2-derived PGE₂production: functional significance

Abdullah

Pedraza²,

McGiff³

et al. 2008

American Journal of Physiology-Renal Physiology

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“…Several studies showed that a renal concentrating defect persists in hypercalcemic animals despite elevated plasma AVP in response to dehydration (4,39,57). Thus reduced responsiveness of the collecting duct to vasopressin appears to be an important cause of polyuria in hypercalcemia, and this view has been supported by several lines of evidence, such as changes of adenylate cyclase activities, cAMP levels, and protein kinase activity (2,9,22,47). Consistent with this view, Earm et al (14) and Sands et al (55) recently demonstrated that vasopressin-regulated water channel aquaporin-2 (AQP2) protein levels were downregulated and AQP2 targeting to the apical plasma membrane of the collecting duct principal cell was also somewhat reduced in hypercalcemia.…”

mentioning

confidence: 95%

Reduced expression of Na-K-2Cl cotransporter in medullary TAL in vitamin D-induced hypercalcemia in rats

Wang

Kwon

et al. 2002

American Journal of Physiology-Renal Physiology

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Chronic hypercalcemia (HC) is accompanied by urinary concentration defects, and functional studies indicate defects in the thick ascending limb (TAL). We hypothesize that dysregulation of renal sodium transporters may play an important role in this. Vitamin D-induced HC in rats resulted in polyuria, natriuresis, and phosphaturia. Immunoblotting revealed a marked reduction in the abundance of rat type 1 bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1) in inner stripe of the outer medullary (ISOM; 36 ± 5%) and whole kidney (51 ± 11%) in HC. Consistent with this finding, immunocytochemistry and immunoelectron microscopy demonstrated reduced BSC-1 labeling of the apical plasma membrane. Immunoblotting and immunohistochemical labeling of the K channel Kir 1.1 (ROMK) was also reduced in HC. In contrast, there were no reductions in the expression of Na/H exchanger (NHE)3 and Na,K-ATPase in ISOM. The abundance of the proximal tubule type II Na-Picotransporter (NaPi-2) (but not Na,K-ATPase and NHE3) was significantly reduced (25 ± 4%), consistent with a dramatic increase in urinary phosphate excretion. In conclusion, 1) the reduced abundance of BSC-1 and ROMK in TAL is likely to play a major role in the urinary concentration defects associated with HC and 2) the reduced abundance of NaPi-2 is likely to play a role in the increased urinary phosphate excretion.

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Mechanism of the Polyuria of Hypercalcemia

Cited by 33 publications

References 15 publications

Influence of Parathyroidectomy and Calcium on Rat Renal Function

Influence of Parathyroidectomy and Calcium on Rat Renal Function

Calcium-sensing receptor signaling pathways in medullary thick ascending limb cells mediate COX-2-derived PGE₂production: functional significance

Reduced expression of Na-K-2Cl cotransporter in medullary TAL in vitamin D-induced hypercalcemia in rats

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Mechanism of the Polyuria of Hypercalcemia

Cited by 33 publications

References 15 publications

Influence of Parathyroidectomy and Calcium on Rat Renal Function

Influence of Parathyroidectomy and Calcium on Rat Renal Function

Calcium-sensing receptor signaling pathways in medullary thick ascending limb cells mediate COX-2-derived PGE2production: functional significance

Reduced expression of Na-K-2Cl cotransporter in medullary TAL in vitamin D-induced hypercalcemia in rats

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Calcium-sensing receptor signaling pathways in medullary thick ascending limb cells mediate COX-2-derived PGE₂production: functional significance