Mechanism of Formation of Human Calcium Oxalate Renal Stones on Randall's Plaque

Abstract

Although calcium oxalate (CaOx) renal stones are known to grow attached to renal papillae, and specifically to regions of papillae that contain Randall's plaque (interstitial apatite deposits), the mechanisms of stone overgrowth on plaque are not known. To investigate the problem, we have obtained biopsy specimens from two stone patients that included an attached stone along with its tissue base and have studied the ultrastructural features of the attachment point using light and transmission electron microscopy, Fourier transform infrared spectroscopy (m-FTIR), and immunohistochemical analysis. The epithelium is disrupted at the attachment site. The denuded plaque that borders on the urinary space attracts an envelope of ribbon-like laminates of crystal and organic matrix arising from urine ions and molecules. Into the matrix of this ribbon grow amorphous apatite crystals that merge with and give way to the usual small apatite crystals imbedded in stone matrix; eventually CaOx crystals admix with apatite and become the predominant solid phase. Over time, urine calcium and oxalate ions gradually overgrow on the large crystals forming the attached stone. Anat Rec, 290:1315Rec, 290: -1323Rec, 290: , 2007 2007 Wiley-Liss, Inc.

Renal Intratubular Crystals and Hyaluronan Staining Occur in Stone Formers with Bypass Surgery but not with Idiopathic Calcium Oxalate Stones

“…These new findings strongly support the idea that ICSFs and bypass patients form CaOx stones by means of two different mechanisms: ICSFs by means of overgrowth on Randall's plaque (Evan et al, 2007a) vs. IMCD deposits in bypass patients. The finding of hyaluronan in bypass but not ICSF patients confirms prior reports of hyaluronan expression being associated with crystal retention and is the first such demonstration in human stone formers.…”

“…They in all probability are not there, and other mechanisms are responsible for common CaOx stones. One such mechanism documented in human tissue is overgrowth of oxalate crystals at sites where Randall's plaque is exposed to urine by virtue of urothelial cell denudation (Evan et al, 2007a). All in all, the idea of IMCD or BD crystals as a nidus for common CaOx stone formation appears unsupported.…”

“…The absence of intratubular crystals in ICSFs is a crucial negative upon which one can erect a pathogenetic scheme for their stone formation, for example, CaOx overgrowth on plaque Evan et al, 2007a).…”

Role of proximal tubule in the hypocalciuric response to thiazide of patients with idiopathic hypercalciuria

“…The fact that there is only one overnight urine sample per patient in each study phase limits the ability for changes to reach significance at that time period. Although decreases in both types of SS have importance for prevention of Ca stones, CaP may be of particular importance, as even for stones composed primarily of CaOx, the initiating phase is CaP (15).…”

“…TZs should be an ideal treatment for this abnormality, by potentially normalizing Ca reabsorption in the proximal tubule. Since overgrowth on exposed plaque surface is the major way by which idiopathic CaOx stones form (15), decreasing plaque formation may be a second mechanism by which TZs can prevent recurrent stones, in addition to lowering urine Ca.…”