JOURNAL ARTICLE

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

Saeed R Khan, Benjamin K Canales
Urolithiasis 2015, 43 Suppl 1: 109-23
25119506
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, and hypocitraturia), renal stress or trauma, and perhaps even the normal aging process lead to transformation of renal epithelial cells into an osteoblastic 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 sub-epithelial 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.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
25119506
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"