Reduction of vitamin D induced stone formation by calcium

Strohmaier, Walter; Seeger, Ruth; Oßwald, Hartmut; Bichler, K.-H.

doi:10.1007/bf00297199

Cited by 4 publications

(3 citation statements)

References 10 publications

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“…A recent study of calcification in mice deficient in osteopontin (OPN) and/or Tamm-Horsfall protein (THP) showed that 10% of the mice lacking OPN and 14.3% of the mice lacking THP spontaneously form interstitial deposits of CaP within the renal papillae (20). Experimental induction of hypercalciuria in rats by administration of vitamin D also resulted in the intratubular deposition of CaP (24). Similarly, weanling rats given AIN-76 diet became hypercalciuric and produced intratubular concretions of CaP (13).…”

Section: Discussionmentioning

confidence: 97%

Calcium oxalate crystal deposition in kidneys of hypercalciuric mice with disrupted type IIa sodium-phosphate cotransporter

Khan¹,

Glenton²

2008

American Journal of Physiology-Renal Physiology

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The most common theories about the pathogenesis of idiopathic kidney stones consider precipitation of calcium phosphate (CaP) within the kidneys critical for the development of the disease. We decided to test the hypothesis that a CaP substrate can promote the deposition of calcium oxalate (CaOx) in the kidneys. Experimental hyperoxaluria was induced by feeding glyoxylate to male mice with knockout (KO) of NaP(i) IIa (Npt2a), a sodium-phosphate cotransporter. Npt2a KO mice are hypercalciuric and produce CaP deposits in their renal tubules. Experimental hyperoxaluria led to CaOx crystalluria in both the hypercalciuric KO mice and the normocalciuric control B6 mice. Only the KO mice produced CaOx crystal deposits in their kidneys, but the CaOx crystals deposited separately from the CaP deposits. Perhaps CaP deposits were not available for a CaOx overgrowth. These results also validate earlier animal model observations that showed that CaP substrate is not required for renal deposition of CaOx and that other factors, such as local supersaturation, may be involved. The absence of CaOx deposition in the B6 mice despite extreme hyperoxaluria also signifies the importance of both calcium and oxalate in the development of CaOx nephrolithiasis.

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Section: Discussionmentioning

confidence: 97%

Calcium oxalate crystal deposition in kidneys of hypercalciuric mice with disrupted type IIa sodium-phosphate cotransporter

Khan¹,

Glenton²

2008

American Journal of Physiology-Renal Physiology

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“…100 Administration of 1,25-dihydroxycholecalciferol alone resulted in the formation of CaP concretions in the kidney. 101 Concretion formation was reduced by calcium antagonist 1,4 dihydronaphthyridine. Deposition of CaP resulted in impaired renal function.…”

Section: Animal Model Studiesmentioning

confidence: 99%

Crystal-induced inflammation of the kidneys: results from human studies, animal models, and tissue-culture studies

2004

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Calcium oxalate (CaOx), calcium phosphate (CaP), and uric acid or urate are the most common crystals seen in the kidneys. Most of the crystals evoke an inflammatory response leading to fibrosis, loss of nephrons, and eventually to chronic renal failure. Of the three, CaOx monohydrate is the most reactive, whereas some forms of CaP do not evoke any discernible response. Reactive oxygen species are produced during the interactions between the crystals and renal cells and are responsible for the various cellular responses. CaOx crystals generally form in the renal tubules. Exposure of renal epithelial cells to CaOx crystals results in the increased synthesis of osteopontin, bikunin, heparan sulfate, monocyte chemoattractant protein 1 (MCP-1), and prostaglandin (PG) E2, which are known to participate in inflammatory processes and in extracellular matrix production. CaOx crystal deposition in rat kidneys also activates the renin-angiotensin system. Both Ox and CaOx crystals selectively activate p38 mitogen-activated protein kinase (MAPK) in exposed tubular cells. CaP crystals can form in the tubular lumen, tubular cells, or tubular basement membrane. Renal epithelial cells exposed to brushite crystals produce MCP-1. Basic CaP and calcium pyrophosphate dihydrate induce mitogenesis in fibroblasts, stimulate production of PGE2, and up-regulate the synthesis of metalloproteinases (MMP) while down-regulating the production of inhibitors of MMPs through activation of p42/44 MAPK. Deposition of urate crystals in the kidneys becomes associated with renal tubular atrophy, interstitial fibrosis, and development of inflammatory infiltrate. Renal epithelial cells exposed to uric acid crystals synthesize MCP-1 as well as PGE2. Monocytes or neutrophils exposed to urate crystals produce tumor necrosis factor alpha, interleukin-1 (IL-1), IL-6, and IL-8. Expression of IL-8 is mediated through extracellular signal-regulated kinase 1 (ERK-1)/ERK-2 and nuclear transcription factors activated protein 1 and nuclear factor kappabeta. Urate crystals also stimulate the macrophages to produce MMPs.

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“…Some patients with this disorder have lower levels of PTH in the absence of changes in 1␣,25(OH) 2 vitamin D 3 (4), whereas, other forms of normocalcemic hypercalciuria in humans may involve disordered regulation of 1␣,25(OH) 2 vitamin D 3 (3). In some cases, hypercalciuria may lead to kidney stone formation (16,18,38). Our results predict that patients with idiopathic hypercalciuria associated with lower levels of PTH may have reduced expression of ClC-5, which in turn would contribute to enhanced renal calcium excretion.…”

Section: Discussionmentioning

confidence: 99%

PTH regulates expression of ClC-5 chloride channel in the kidney

Silva

Blaisdell

Guggino³

et al. 2000

American Journal of Physiology-Renal Physiology

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Mutations in the chloride channel, ClC-5, have been described in several inherited diseases that result in the formation of kidney stones. To determine whether ClC-5 is also involved in calcium homeostasis, we investigated whether ClC-5 mRNA and protein expression are modulated in rats deficient in 1alpha,25(OH)(2) vitamin D(3) with and without thyroparathyroidectomy. Parathyroid hormone (PTH) was replaced in some animals. Vitamin D-deficient, thyroparathyrodectomized rats had lower serum and higher urinary calcium concentrations compared with control animals as well as lower serum PTH and calcitonin concentrations. ClC-5 mRNA and protein levels in the cortex decrease in vitamin D-deficient, thyroparathyroidectomized rats compared with both control and vitamin D-deficient animals. ClC-5 mRNA and protein expression increase near to control levels in vitamin D-deficient, thyroparathyroidectomized rats injected with PTH. No significant changes in ClC-5 mRNA and protein expression in the medulla were detected in any experimental group. Our results suggest that PTH modulates the expression of ClC-5 in the kidney cortex and that neither 1alpha,25(OH)(2) vitamin D(3) nor PTH regulates ClC-5 expression in the medulla. The pattern of expression of ClC-5 varies with urinary calcium. Animals with higher urinary calcium concentrations have lower levels of ClC-5 mRNA and protein expression, suggesting that the ClC-5 chloride channel plays a role in calcium reabsorption.

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Reduction of vitamin D induced stone formation by calcium

Cited by 4 publications

References 10 publications

Calcium oxalate crystal deposition in kidneys of hypercalciuric mice with disrupted type IIa sodium-phosphate cotransporter

Calcium oxalate crystal deposition in kidneys of hypercalciuric mice with disrupted type IIa sodium-phosphate cotransporter

Crystal-induced inflammation of the kidneys: results from human studies, animal models, and tissue-culture studies

PTH regulates expression of ClC-5 chloride channel in the kidney

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