Effects of hypercalcemia on calcium and phosphate ultrafilterability and tubular reabsorption in the rat

Harris, Carol; Sutton, R. A.; Dirks, John H.

doi:10.1152/ajprenal.1977.233.3.f201

Cited by 13 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our computed value in the early distal tubule (1.9) is higher than the value (1.4) reported by LeGrimellec et al (35) during plasma Ca 2ϩ loading; the reason may be that Ca 2ϩ loading induces changes in calcium ultrafilterability, proximal tubule reabsorption, and interstitial Ca 2ϩ concentration gradients that our model does not account for (26). Conversely, under hypocalcemic conditions (simulated by lowering filtered and interstitial [Ca 2ϩ ] by 10%), the computed Ca 2ϩ -to-Na ϩ TF/UF ratio is predicted to decrease, since Ca 2ϩ reabsorption is augmented (Fig.…”

Section: Regulation By Pthcontrasting

confidence: 94%

Regulation of calcium reabsorption along the rat nephron: a modeling study

Edwards

2015

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

We expanded a mathematical model of transepithelial transport along the rat nephron to include the transport of Ca(2+) and probe the impact of calcium-sensing mechanisms on Ca(2+) reabsorption. The model nephron extends from the medullary thick ascending limb (mTAL) to the inner medullary collecting duct (IMCD). Our model reproduces several experimental findings, such as measurements of luminal Ca(2+) concentrations in cortical tubules, and the effects of furosemide or deletion of the transient receptor potential channel vanilloid subtype 5 (TRPV5) on urinary Ca(2+) excretion. In vitro microperfusion of rat TAL has demonstrated that activation of the calcium-sensing receptor CaSR lowers the TAL permeability to Ca(2+), PCa (TAL) (Loupy A, Ramakrishnan SK, Wootla B, Chambrey R, de la Faille R, Bourgeois S, Bruneval P, Mandet C, Christensen EI, Faure H, Cheval L, Laghmani K, Collet C, Eladari D, Dodd RH, Ruat M, Houillier P. J Clin Invest 122: 3355, 2012). Our results suggest that this regulatory mechanism significantly impacts renal Ca(2+) handling: when plasma Ca(2+) concentration ([Ca(2+)]) is raised by 10%, the CaSR-mediated reduction in PCa (TAL) per se is predicted to enhance urinary Ca(2+) excretion by ∼30%. If high [Ca(2+)] also induces renal outer medullary potassium (ROMK) inhibition, urinary Ca(2+) excretion is further raised. In vitro, increases in luminal [Ca(2+)] have been shown to activate H(+)-ATPase pumps in the outer medullary CD and to lower the water permeability of IMCD. Our model suggests that if these responses exhibit the sigmoidal dependence on luminal [Ca(2+)] that is characteristic of CaSR, then the impact of elevated Ca(2+) levels in the CD on urinary volume and pH remains limited. Finally, our model suggests that CaSR inhibitors could significantly reduce urinary Ca(2+) excretion in hypoparathyroidism, thereby reducing the risk of calcium stone formation.

show abstract

Section: Regulation By Pthcontrasting

confidence: 94%

Regulation of calcium reabsorption along the rat nephron: a modeling study

Edwards

2015

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

show abstract

“…Consistent with this finding, maximal urine flow, another parameter of distal delivery, also increased. This is in accord with micropuncture studies reporting inhibition of proximal NaCl and water reab sorption in thyroparathyroidectomized rats [13] and mongrel dogs [9,14], Other investigators also demon strated a decrease in proximal reabsorption of sodium and water with hypercalcemia [6,15], while some re ported no change [16,17], Extracellular volume status that is known to influence proximal reabsorption of salt and water did not change during the study as urinary losses were replaced with equal amounts of water orally. Calcium was infused in 250 ml of 5% dextrose solution, which would expand ECV only to a negligible amount, while urinary loss of Na equivalent to 120 ml occurred.…”

Section: Discussionsupporting

confidence: 76%

“…There is no indication that mod erate changes in the level of calcium would affect this secretion. Moreover, in animal studies similar levels of calcium did not change GFR [5][6][7], while higher levels depressed it [8,9], In humans, no change [3], as well as slight elevation of GFR [6], have been reported. Although higher levels of calcium may cause hypertension [10], most authors also found no changes in blood pressure [1,2,5,11].…”

Section: Discussionmentioning

confidence: 92%

Effect of Elevated Calcium Levels on Segmental Tubular Sodium Reabsoφtion in Normal Man

Yalnız

Özbasli²,

Akçiçek³

et al. 1996

Nephron

View full text Add to dashboard Cite

The aim of the present study was to assess the effect of calcium infusion on segmental tubular reabsorption in humans using lithium clearance, along with creatinine and free water clearances during maximal water diuresis. In 8 healthy volunteers, a 20-min 5 mg/kg calcium infusion that increased serum calcium levels from 2.27 ± 0.07 to 2.87 ± 0.07 mmol/l (p < 0.01) was followed by a 60-min 3 mg/kg infusion for maintenance. During the experimental period, blood pressure did not change. Maximal urine flow increased from 15.6 ± 2.4 to 20.8 ± 2.8 ml/min (p < 0.01), while clearance of sodium increased from 1.5 ± 0.4 to 3.7 ± 0.9 ml/min (p < 0.001). Lithium clearance showed an increase of 7.4 ml/min, pointing to a suppression of proximal reabsorption. Free water clearance also increased from 11.5 ± 3.7 to 14.4 ± 3.9 ml/min, indicating an increase in TALH reabsorption which was attributed to increased sodium and water reaching this segment. Time control studies showed no significant changes in the parameters measured except for potassium excretion. Potassium excretion during calcium infusion was somewhat lower than during the control studies. The data support the view that an increase in serum calcium concentration leads to a decrease in proximal tubular reabsorption as indicated by lithium clearance while a decrease in reabsorption in the collecting duct could well add to the diuretic properties of calcium.

show abstract

“…Note that up to the DT calcium reabsorption is largely unrelated to the calcium balance of the moment. Phosphate is also reabsorbed extensively (75%) in the PT, and much less in the distal tubule (10%) and the CD (3 7%) [33,34,65]. With phosphate, an additional complicating factor is the threshold above which it is excreted quantitatively.…”

Section: Concentration Profilesmentioning

confidence: 99%

Intratubular crystallization events

Kok¹

1997

World J Urol

View full text Add to dashboard Cite

Can urolithiasis start as an intratubular event? Under severe hyperoxaluric conditions in animal models at least crystal formation can. Recently models have been presented that assess the chances of crystal formation under more normal conditions. These models describe changes in fluid composition as this passes through the nephron, these conditions being simulated in in vitro experiments. It appears that under naturally occurring intratubular conditions calcium-salt crystallization takes place within the time tubular fluid normally spends in the nephron. Precipitation starts with a calcium-phosphate phase under conditions found in the thin lambs. This crystalline phase then (partly) dissolves when collecting duct conditions are used, thereby inducing formation of calcium oxalates. Under these conditions the latter increase in size by way of crystal growth and agglomeration. Large particle formation and cell adhesion can eventually result in particle retention and subsequent stone formation. Viewing urolithiasis as originally an intratubular event has consequences for in vitro experiments and treatments, which are discussed in this paper.

show abstract

Effects of hypercalcemia on calcium and phosphate ultrafilterability and tubular reabsorption in the rat

Cited by 13 publications

References 0 publications

Regulation of calcium reabsorption along the rat nephron: a modeling study

Regulation of calcium reabsorption along the rat nephron: a modeling study

Effect of Elevated Calcium Levels on Segmental Tubular Sodium Reabsoφtion in Normal Man

Intratubular crystallization events

Contact Info

Product

Resources

About

Effects of hypercalcemia on calcium and phosphate ultrafilterability and tubular reabsorption in the rat

Cited by 13 publications

References 0 publications

Regulation of calcium reabsorption along the rat nephron: a modeling study

Regulation of calcium reabsorption along the rat nephron: a modeling study

Effect of Elevated Calcium Levels on Segmental Tubular Sodium Reabso&phi;tion in Normal Man

Intratubular crystallization events

Contact Info

Product

Resources

About

Effect of Elevated Calcium Levels on Segmental Tubular Sodium Reabsoφtion in Normal Man