Association of Randall Plaque With Collagen Fibers and Membrane Vesicles

Abstract

Background Idiopathic calcium oxalate (CaOx) kidney stones develop by deposition of CaOx crystals on Randall's plaques (RP). Mechanisms involved in RP formation are still unclear. Objective It is our hypotheses that RP formation is similar to vascular calcification involving components of extracellular matrix including membrane bound vesicles (MV) and collagen fibers. In order to verify our hypothesis we critically examined renal papillary tissue from stone patients. Methods 4 mm cold-cup biopies of renal papillae were performed on fifteen idiopathic stone patients undergoing PCNL. Tissue was immediately fixed and processed for analyses by various light and electron microscopic techniques. Results and Limitations Spherulitic CaP crystals, the hallmark of RP's, were seen in all samples examined. They were seen in interstitium as well as laminated basement membrane of tubular epithelia. Large crystalline deposits comprised of dark elongated strands mixed with spherulites. Strands showed banded patterns similar to collagen. Crystal deposits were surrounded by collagen fibers and membrane bound vesicles. Energy dispersive x-ray microanalyses (EDX) and electron diffraction identified the crystals as hydroxyapatite. The number of kidneys examined is small and urinary data was not available for all the patients. Conclusions Results presented here show that crystals in the Randall's plaques are associated with both the collagen as well as MV. Collagen fibers appeared calcified and vesicles contained crystals. We conclude that crystal deposition in renal papillae may have started with membrane vesicle induced nucleation and grew by addition of crystals on the periphery within a collagen framework.

Vascular theory of the formation of Randall plaques

“…This peripheral growth in calcification continues through heterogeneous nucleation of these crystals and the surrounding milieu. This process of ectopic calcification is similar to pathologic calcifications within atherosclerotic lesions [13].…”

Kidney Stones and Cardiovascular Events

“…These precipitations would in turn cause the clinical sequelae of AMI and stroke observed herein. Consistent with this, a recent study found that the formation of Randall plaque (the inciting stone nidus) is similar in composition to vascular plaque (24). Moreover, inhibitors of calcification are found both in blood and urine, such as pyrophosphates (25).…”

Revisiting Randall's plaque

“…Khan et al studied papillary biopsies from ICSF with light microscopy, TEM, SEM, and IHC for osteopontin and collagen [31]. Plaque mineral does not come in direct contact with urine.…”

“…There is loss of epithelium at plaque surface. This exposes a fibrous layer and plaque is beneath this fibrous layer [31]. Outer surface of plaque is composed of small spherical units mixed with long thin fibers running between them.…”

“…Spherical units in the basement membrane are closely associated with membrane bound vesicles and those in the interstitium with collagen. Crystal process may be initiated by membrane bound vesicles in the presence of supersaturation and further growth of plaque can occur by addition of crystals at the periphery in the framework of collagen, leading to biomineralization of collagen [31].…”