What is nephrocalcinosis?

Shavit, Linda; Jaeger, Philippe; Unwin, Robert J.

doi:10.1038/ki.2015.76

Cited by 79 publications

(82 citation statements)

References 73 publications

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“…While other experimental models have clearly demonstrated OPN’s anti-calcific property, our findings are unique in that they establish OPN as a simultaneous protector of both vascular and renal calcification. This is particularly noteworthy as clinical studies show a strong correlation between kidney stone formation and VC, and pathogenic links between nephrocalcinosis and VC have been hypothesized 1, 36 . Also, previous in vivo calcification models utilizing OPN KO animals have induced calcification in various ways such as graft implantation or oxalate administration (given orally or via injection) 37–39 .…”

Section: Discussionmentioning

confidence: 96%

“…This accumulation of calcium in the kidney is due to increased urinary excretion of calcium, phosphorus, and/or oxalate in combination with a loss of protective urinary inhibitors of mineralization. There are many underlying diseases that cause nephrocalcinosis and depending on the etiology, nephrocalcinosis can cause progressive renal dysfunction and end stage renal disease (ESRD) 1 . Similar to nephrocalcinosis, vascular calcification (VC) is caused by an imbalance in pro-calcific and anti-calcific factors.…”

Section: Introductionmentioning

confidence: 99%

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Osteopontin protects against high phosphate-induced nephrocalcinosis and vascular calcification

Paloian

Leaf

Giachelli

2016

Kidney International

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Pathologic calcification is a significant cause of increased morbidity and mortality in patients with chronic kidney disease (CKD). The precise mechanisms of ectopic calcification are not fully elucidated, but it is known to be caused by an imbalance of pro-calcific and anti-calcific factors. In the CKD population, an elevated phosphate burden is both highly prevalent and a known risk factor for ectopic calcification. Here we tested whether osteopontin, an inhibitor of calcification, protects against high phosphate load-induced nephrocalcinosis and vascular calcification. Osteopontin knockout mice were placed on a high phosphate diet for eleven weeks. Osteopontin deficiency together with phosphate overload caused uremia, nephrocalcinosis characterized by substantial renal tubular and interstitial calcium deposition, and marked vascular calcification when compared to controls. While the osteopontin-deficient mice did not exhibit hypercalcemia or hyperphosphatemia, they did show abnormalities in the mineral metabolism hormone fibroblast growth factor 23. Thus, endogenous osteopontin plays a critical role in the prevention of phosphate induced nephrocalcinosis and vascular calcification in response to high phosphate load. A better understanding of osteopontin’s role in phosphate induced calcification will hopefully lead to better biomarkers and therapies for this disease, especially in patients with CKD and other at risk populations.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Osteopontin protects against high phosphate-induced nephrocalcinosis and vascular calcification

Paloian

Leaf

Giachelli

2016

Kidney International

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“…The RCALC1 phenotype has similarities to human NC, which includes the interstitial deposition of calcium phosphate in the renal papillae . For example, high‐resolution Fourier transform infrared microspectroscopy and electron diffraction studies have revealed that calcium phosphate crystals are the major component of Randall's plaque, which are the areas of the renal papillae that contain interstitial calcium phosphate deposits that provide a nidus of urothelial surface for calcium oxalate deposition .…”

Section: Resultsmentioning

confidence: 99%

“…Renal calcification may occur in the kidney parenchyma (nephrocalcinosis [NC]) or the collecting system (nephrolithiasis [NL], ie, kidney stones) . NL and NC affect ∼10% of the adult Western population by the age of 70 years, although such distinctions may be difficult in patients who may develop both NL and NC, and it has been reported that >50% to 70% of patients with kidney stones will have NC .…”

Section: Introductionmentioning

confidence: 99%

Mice with a Brd4 Mutation Represent a New Model of Nephrocalcinosis

Gorvin

Loh

Stechman

et al. 2019

Journal of Bone and Mineral Research

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Nephrolithiasis (NL) and nephrocalcinosis (NC), which comprise renal calcification of the collecting system and parenchyma, respectively, have a multifactorial etiology with environmental and genetic determinants and affect ∼10% of adults by age 70 years. Studies of families with hereditary NL and NC have identified >30 causative genes that have increased our understanding of extracellular calcium homeostasis and renal tubular transport of calcium. However, these account for <20% of the likely genes that are involved, and to identify novel genes for renal calcification disorders, we investigated 1745 12‐month‐old progeny from a male mouse that had been treated with the chemical mutagen N‐ethyl‐N‐nitrosourea (ENU) for radiological renal opacities. This identified a male mouse with renal calcification that was inherited as an autosomal dominant trait with >80% penetrance in 152 progeny. The calcification consisted of calcium phosphate deposits in the renal papillae and was associated with the presence of the urinary macromolecules osteopontin and Tamm‐Horsfall protein, which are features found in Randall's plaques of patients with NC. Genome‐wide mapping located the disease locus to a ∼30 Mbp region on chromosome 17A3.3‐B3 and whole‐exome sequence analysis identified a heterozygous mutation, resulting in a missense substitution (Met149Thr, M149T), in the bromodomain‐containing protein 4 (BRD4). The mutant heterozygous (Brd4+/M149T) mice, when compared with wild‐type (Brd4+/+) mice, were normocalcemic and normophosphatemic, with normal urinary excretions of calcium and phosphate, and had normal bone turnover markers. BRD4 plays a critical role in histone modification and gene transcription, and cDNA expression profiling, using kidneys from Brd4+/M149T and Brd4+/+ mice, revealed differential expression of genes involved in vitamin D metabolism, cell differentiation, and apoptosis. Kidneys from Brd4+/M149T mice also had increased apoptosis at sites of calcification within the renal papillae. Thus, our studies have established a mouse model, due to a Brd4 Met149Thr mutation, for inherited NC. © 2019 American Society for Bone and Mineral Research.

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“…It can be seen in a variety of congenital and acquired diseases. 1 Diagnosis is often made incidentally by imaging such as plain abdominal radiography, kidney ultrasonography and abdominal computed tomography. 2 In general, nephrocalcinosis is recognized as systemic disease and appropriate evaluation is needed to clarify underlying disease.…”

Section: Clinical Descriptionmentioning

confidence: 99%