Calcification in the human renal papilla: An electron‐microscope study

Weller, Roy O.; Nester, Brian A; Cooke, S. A. R.

doi:10.1002/path.1711070308

Cited by 21 publications

(12 citation statements)

References 14 publications

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“…They found alizarin red positive laminated spherules in the interstitium which on closer examination by TEM were found associated with collagen fibers in the interstitium as well as basement membrane of the collecting ducts. Cooke and associates [14,15] studied 62 normal kidneys and found calcification in 4, which was invariably located in the basement membrane of the loops of Henle from where it extended into the medullary interstitium. Some collecting ducts and blood vessels were also involved.…”

Section: Randall’s Theory Of Stone Formationmentioning

confidence: 99%

Unified theory on the pathogenesis of Randall’s plaques and plugs

2014

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Kidney stones develop attached to sub-epithelial plaques of calcium phosphate (CaP) crystals (termed Randall’s plaque) and/or form as a result of occlusion of the openings of the Ducts of Bellini by stone forming crystals (Randall’s plugs). These plaques and plugs eventually extrude into the urinary space, acting as a nidus for crystal overgrowth and stone formation. To better understand these regulatory mechanisms and the pathophysiology of idiopathic calcium stone disease, this review provides in-depth descriptions of the morphology and potential origins of these plaques and plugs, summarizes existing animal models of renal papillary interstitial deposits, and describes factors that are believed to regulate plaque formation and calcium overgrowth. Based on evidence provided within this review and from the vascular calcification literature, we propose a “unified” theory of plaque formation – one similar to pathological biomineralization observed elsewhere in the body. Abnormal urinary conditions (hypercalciuria, hyperoxaluria, hypocitraturia), renal stress or trauma, and perhaps even the normal aging process leads to transformation of renal epithelial cells into an osteblastic phenotype. With this de-differentiation comes an increased production of bone specific proteins (i.e. osteopontin), a reduction in crystallization inhibitors (such as fetuin and matrix-gla-protein), and creation of matrix vesicles, which support nucleation of CaP crystals. These small deposits promote aggregation and calcification of surrounding collagen. Mineralization continues by calcification of membranous cellular degradation products and other fibers until the plaque reaches the papillary epithelium. Through the activity of matrix metalloproteinases or perhaps by brute physical force produced by the large subepithelial crystalline mass, the surface is breached and further stone growth occurs by organic matrix-associated nucleation of CaOx or by the transformation of the outer layer of CaP crystals into CaOx crystals. Should this theory hold true, developing an understanding of the cellular mechanisms involved in progression of a small, basic interstitial plaque to that of an expanding, penetrating plaque could assist in the development of new therapies for stone prevention.

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Section: Randall’s Theory Of Stone Formationmentioning

confidence: 99%

Unified theory on the pathogenesis of Randall’s plaques and plugs

2014

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“…Decades of further studies have resulted from Randall's original observations. [35][36][37][38][39][40][41][42][43][44][45][46][47] The theory of Randall does not specifically explain why or where these plaques form. However, vascular considerations and evidence support an alternative hypothesis to primary uriniferous stone formation.…”

Section: Physiological Evidencementioning

confidence: 99%

The Primary Stone Event: A New Hypothesis Involving a Vascular Etiology

et al. 2004

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Numerous inconsistencies exist between current theories of the initial event in nephrolithiasis formation and empirical observational data on stone disease. Our review of the literature and our study of the cholesterol content of renal stones support a new theory regarding the initial stone forming event. We base this novel hypothesis on multiple epidemiological, physiological, anatomical and clinical observations. Further studies are required to confirm this hypothesis and its clinical usefulness.

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“…For the purpose of this review I will continue to use RP1 and RP2 as originally proposed. RP1 is suggested to start as laminated microspheres of poorly crystalline biological apatite in basement membrane of the loops of Henle [68, 69], or interstitium in association with vasa recta [70] or collecting ducts [20]. These microspheres are suggested to migrate to the subepithelial space, coalesce with others and materialize as RP1.…”

Section: Renal Cellular and Molecular Eventsmentioning

confidence: 99%

Is oxidative stress, a link between nephrolithiasis and obesity, hypertension, diabetes, chronic kidney disease, metabolic syndrome?

2012

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Epidemiological studies have provided the evidence for association between nephrolithiasis and a number of cardiovascular diseases including hypertension, diabetes, chronic kidney disease, metabolic syndrome. Many of the co-morbidities may not only lead to stone disease but also be triggered by it. Nephrolithiasis is a risk factor for development of hypertension and have higher prevalence of diabetes mellitus and some hypertensive and diabetic patients are at greater risk for stone formation. An analysis of the association between stone disease and other simultaneously appearing disorders, as well as factors involved in their pathogenesis, may provide an insight into stone formation and improved therapies for stone recurrence and prevention. It is our hypothesis that association between stone formation and development of co-morbidities is a result of certain common pathological features. Review of the recent literature indicates that production of reactive oxygen species (ROS) and development of oxidative stress (OS) may be such a common pathway. OS is a common feature of all cardiovascular diseases (CVD) including hypertension, diabetes mellitus, atherosclerosis and myocardial infarct. There is increasing evidence that ROS are also produced during idiopathic calcium oxalate (CaOx) nephrolithiasis. Both tissue culture and animal model studies demonstrate that ROS are produced during interaction between CaOx/calcium phosphate (CaP) crystals and renal epithelial cells. Clinical studies have also provided evidence for the development of oxidative stress in the kidneys of stone forming patients. Renal disorders which lead to OS appear to be a continuum. Stress produced by one disorder may trigger the other under the right circumstances.

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Calcification in the human renal papilla: An electron‐microscope study

Cited by 21 publications

References 14 publications

Unified theory on the pathogenesis of Randall’s plaques and plugs

Unified theory on the pathogenesis of Randall’s plaques and plugs

The Primary Stone Event: A New Hypothesis Involving a Vascular Etiology

Is oxidative stress, a link between nephrolithiasis and obesity, hypertension, diabetes, chronic kidney disease, metabolic syndrome?

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