Role of Osteogenesis in the Formation of <scp>R</scp>andall's Plaques

Khan, Saeed R.; Gambaro, Giovanni

doi:10.1002/ar.23275

Cited by 17 publications

(12 citation statements)

References 18 publications

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“…In fact, vasa recta and epithelial cells of some the uriniferous tubules in RP+ specimen show either positive or stronger localization of NCPs than that observed in the background within the same tissue section ( Fig 9 ) and corroborates with earlier reports [ 16 , 28 ]. Meanwhile, the positive staining of these tubular cells may indicate an active intracellular synthesis of NCPs, which is in accordance with the hypothesis of osteoblast phenotype change in the distal region [ 12 , 41 ]. However, the strong expression of BSP, OC, and OPN in vasa recta and other tubules ( Fig 9 ) belonging to the proximal medullo-papillary complex suggests a different source of NCPs, that is, NCPs may be delivered from proximal renal tubules or vasa recta to the distal region.…”

Section: Discussionsupporting

confidence: 85%

Anatomically-specific intratubular and interstitial biominerals in the human renal medullo-papillary complex

Chen¹,

Hsi²,

Yang³

et al. 2017

PLoS ONE

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Limited information exists on the anatomically-specific early stage events leading to clinically detectable mineral aggregates in the renal papilla. In this study, quantitative multiscale correlative maps of structural, elemental and biochemical properties of whole medullo-papillary complexes from human kidneys were developed. Correlative maps of properties specific to the uriniferous and vascular tubules using high-resolution X-ray computed tomography, scanning and transmission electron microscopy, energy dispersive X-ray spectroscopy, and immunolocalization of noncollagenous proteins (NCPs) along with their association with anatomy specific biominerals were obtained. Results illustrated that intratubular spherical aggregates primarily form at the proximal regions distant from the papillary tip while interstitial spherical and fibrillar aggregates are distally located near the papillary tip. Biominerals at the papillary tip were closely localized with 10 to 50 μm diameter vasa recta immunolocalized for CD31 inside the medullo-papillary complex. Abundant NCPs known to regulate bone mineralization were localized within nanoparticles, forming early pathologic mineralized regions of the complex. Based on the physical association between vascular and urothelial tubules, results from light and electron microscopy techniques suggested that these NCPs could be delivered from vasculature to prompt calcification of the interstitial regions or they might be synthesized from local vascular smooth muscle cells after transdifferentiation into osteoblast-like phenotypes. In addition, results provided insights into the plausible temporal events that link the anatomically specific intratubular mineral aggregates with the interstitial biomineralization processes within the functional unit of the kidney.

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Section: Discussionsupporting

confidence: 85%

Anatomically-specific intratubular and interstitial biominerals in the human renal medullo-papillary complex

Chen¹,

Hsi²,

Yang³

et al. 2017

PLoS ONE

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“…What provokes the formation of Randall’s plaques is unknown. It has been proposed that the formation of Randall’s plaques might be similar to vascular calcification 115,116 (see below).…”

Section: Mechanisms/pathophysiologymentioning

confidence: 99%

Kidney stones

Khan

Pearle

Robertson

et al. 2016

Nat Rev Dis Primers

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671

505

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Kidney stones are mineral deposits in the renal calyces and pelvis that are found free or attached to the renal papillae. They contain crystalline and organic components and are formed when the urine becomes supersaturated with respect to a mineral. Calcium oxalate is the main constituent of most stones, many of which form on a foundation of calcium phosphate called Randall’s plaques, which are present on the renal papillary surface. Stone formation is highly prevalent, with rates of up to 14.8% and increasing, and a recurrence rate of up to 50% within the first 5 years of the initial stone episode. Obesity, diabetes, hypertension and metabolic syndrome are considered risk factors for stone formation, which, in turn, can lead to hypertension, chronic kidney disease and end-stage renal disease. Management of symptomatic kidney stones has evolved from open surgical lithotomy to minimally invasive endourological treatments leading to a reduction in patient morbidity, improved stone-free rates and better quality of life. Prevention of recurrence requires behavioural and nutritional interventions, as well as pharmacological treatments that are specific for the type of stone. There is a great need for recurrence prevention that requires a better understanding of the mechanisms involved in stone formation to facilitate the development of more-effective drugs.

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“…A role in the pathogenesis of Randall's plaques has also been suggested for interstitial cells capable of transdifferentiating along the bone lineage, leading to the hypothesis that nephrocalcinosis could be an osteogenic cell-driven process, similar to that of vascular calcification [64,[165][166][167][168]. Tubular epithelial cells have a well-known ability to differentiate into cells with the mesenchymal phenotype (for instance, renal interstitial myofibroblasts may originate from renal tubular cells undergoing epithelial-mesenchymal transformation) [169].…”

Section: Cell-driven Calcification: the Example Of Vascular Calcificamentioning

confidence: 99%

“…Increasing phosphate concentrations in the VSMCs induce their phenotypic switch to osteoblast-like cells [177,178,184]. In the event of renal failure, phosphate plays a key part in this mechanism [165,168]. Vascular SMCs exposed to pro-calcifying levels of phosphate (akin to what may happen in patients with chronic kidney disease (CKD)) lose their expression of the smooth muscle contractile proteins, SM22α and SMα-actin, and express the bone markers Runx2, OPN, OCN, and ALP instead [178].…”

Section: Phosphatementioning

confidence: 99%

Understanding the Pathophysiology of Nephrocalcinosis

Priante¹,

Ceol²,

Terrin³

et al. 2017

Updates and Advances in Nephrolithiasis - Pathophysiology, Genetics, and Treatment Modalities

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Many in vitro and in vivo studies on the mechanisms underlying calcium nephrolithiasis have provided evidence of a frequently associated condition, i.e., a microscopic renal crystal deposition that can occur within the tubular lumen (intratubular nephrocalcinosis) or in the interstitium (interstitial nephrocalcinosis). Medullary nephrocalcinosis is the typical pattern seen in 98% of cases of human nephrocalcinosis, with calcification clustering around each renal pyramid. It is common in patients with metabolic conditions that predispose them to renal calcium stones. Cortical nephrocalcinosis is rare and usually results from severe destructive disease of the cortex. It has been described in chronic glomerulonephritis, but often in association with another factor, such as an increased calcium ingestion, acute cortical necrosis, chronic pyelonephritis or trauma. The most accredited hypothesis to explain the onset of interstitial nephrocalcinosis is purely physicochemical, relating to spontaneous Ca 2 PO 4 crystallization in the interstitium due to oversaturation of Ca 2 PO 4 salts in this milieu. The theory that nephrocalcinosis is a process driven by osteogenic cells was first proposed by our group. We review nephrocalcinosis in terms of its definition, genetic associations, and putative mechanisms, pointing out how much evidence in the literature suggests that it may have some features in common with, and pathogenic links to vascular calcification.

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Role of Osteogenesis in the Formation of Randall's Plaques

Cited by 17 publications

References 18 publications

Anatomically-specific intratubular and interstitial biominerals in the human renal medullo-papillary complex

Anatomically-specific intratubular and interstitial biominerals in the human renal medullo-papillary complex

Kidney stones

Understanding the Pathophysiology of Nephrocalcinosis

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