No abstract

No 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.

Although often supersaturated with mineral salts such as calcium phosphate and calcium oxalate, normal urine possesses an innate ability to keep them from forming harmful crystals. This inhibitory activity has been attributed to the presence of urinary macromolecules, although controversies abound regarding their role, or lack thereof, in preventing renal mineralization. Here, we show that 10% of the mice lacking osteopontin (OPN) and 14.3% of the mice lacking Tamm-Horsfall protein (THP) spontaneously form interstitial deposits of calcium phosphate within the renal papillae, events never seen in wild-type mice. Lack of both proteins causes renal crystallization in 39.3% of the double-null mice. Urinalysis revealed elevated concentrations of urine phosphorus and brushite (calcium phosphate) supersaturation in THP-null and OPN/ THP-double null mice, suggesting that impaired phosphorus handling may be linked to interstitial papillary calcinosis in THP-but not in OPN-null mice. In contrast, experimentally induced hyperoxaluria provokes widespread intratubular calcium oxalate crystallization and stone formation in OPN/THP-double null mice, while completely sparing the wild-type controls. Whole urine from OPN-, THP-, or double-null mice all possessed a dramatically reduced ability to inhibit the adhesion of calcium oxalate monohydrate crystals to renal epithelial cells. These data establish OPN and THP as powerful and functionally synergistic inhibitors of calcium phosphate and calcium oxalate crystallization in vivo and suggest that defects in either molecule may contribute to renal calcinosis and stone formation, an exceedingly common condition that afflicts up to 12% males and 5% females. kidney stone; urolithiasis; uromodulin CLINICAL KIDNEY STONE DISEASE is classified into a number of forms, each requiring a specific plan for medical treatment. It has only been recently demonstrated through a series of biopsy studies of renal papillae from human stone formers that the different stones can develop through different pathways (7,13). Whether the pathogenetic process leading to stone formation involves interstitial plaque or intratubular crystal deposits, a range of host factors appears to be involved, some acting as facilitators and others as inhibitors. Under normal conditions, there is a fine equilibrium between pro-and anticrystallization forces, which helps keep the kidneys stone-free so that they can carry out important physiological functions. However, when the equilibrium breaks down, urine constituents can precipitate out, allowing insoluble crystals to form. Although the mechanisms that mediate retention of urinary crystals into stones remain poorly defined, it is clear that the degree of urinary supersaturation predicts stone risk and type (24,28,38). Furthermore, the urine of most individuals is frequently supersaturated with calcium oxalate and calcium phosphate. These observations suggest a critical role for urinary supersaturation and inhibitors of crystallization. This paradigm of nephrolithiasis has ...

Brushite stone formers combine the interstitial plaque of calcium oxalate stone formers with the collecting duct apatite plugs found in stone formers with intestinal bypass. Collecting duct injury and interstitial fibrosis are severe. Prominent cortical fibrosis, tubule atrophy, and glomerular pathology seem secondary to the collecting duct plugging. We believe crystallization obstructs and destroys terminal collecting duct segments thereby damaging nephrons, perhaps via intranephronal obstruction, and producing a hitherto unrecognized renal disease.