Clinical Trial: Attached Stone Project: Do Calcium Oxalate Renal Calculi Originate From Randall's Plaque?

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Do Calcium Oxalate Renal Calculi Originate From Randall's Plaque?

Brief Summary: Urolithiasis is a common condition in the United States, and is associated with significant morbidity and even mortality. The most commonly occurring urinary calculi are comprised of calcium oxalate salts, and until recently, the pathogenesis of calcium oxalate calculi was poorly understood. New evidence, however, suggests that the development of calcium oxalate calculi may be intimately associated with hydroxyapatite (HA) plaque, also known as Randall's plaque, which is located on the renal papillae. The investigators have previously demonstrated that Randall's plaque originates in the thin ascending limb of the loop of Henle, and they have shown that Randall's plaque is composed of HA (Evan, Lingeman et al. 2003). As well, the amount of Randall's plaque correlates with elevated levels of urinary calcium and decreased urinary volume, risk factors for the formation of calcium oxalate calculi (Kuo, Lingeman et al. 2003). In the course of these previous studies, the investigators have anecdotally noted that calcium oxalate stones are often found attached to Randall's plaque, an observation that others have reported as well (Prien 1949; Carr 1954; Cifuentes Delatte, Minon-Cifuentes et al. 1987). However, there has been no in-vivo, rigorous documentation of this "attached stone" relationship. Attached calculi represent an important point in the pathogenesis of calcium oxalate calculi, as they correspond to a moment in time where there is a continuum between the HA plaque of Randall and the calcium oxalate stone, thus linking the origin of plaque with the development of stone. A better understanding of the phenomenon of attached calculi will lead to a better understanding of how and why calcium oxalate stones form, which may ultimately direct future interventions to attenuate stone activity.

Detailed Summary:

Urolithiasis is a very common condition in the United States, with an estimated prevalence of 11.7% by age 70. Furthermore, it has been associated with considerable patient morbidity and occasional mortality (Stamatelou, Francis et al. 2003). Direct costs associated with the treatment of renal calculi are enormous, as over 600,000 stone related medical procedures are performed annually in the United States (shock wave lithotripsy (SWL), ureteroscopy (URS), percutaneous nephrolithotomy (PERC), stone removal, ureteral stents, and stone basketing (source: Boston Scientific Corporation). Although the last two decades have seen considerable advances in less invasive techniques for the treatment of symptomatic stone episodes, as well as progress in mitigating the risks of new stone formation, our knowledge of the inciting lesion in human urolithiasis remains rudimentary and much debated.

Until recently, the sequence of events that leads to the formation of urinary calculi were poorly understood, most fundamentally due to the lack of appropriate in-vivo data. Earlier theories of calculogenesis proposed that stones could result from tubular epithelial injury due to oxalate toxicity, a lack of urinary inhibitors of crystal formation or crystal epitaxy on a pre-existing nidus (Khan, Finlayson et al. 1979). Theoretical work on free and fixed particle growth indicated that a transit time from the collecting duct to the bladder of only 10 minutes provided insufficient time for a crystal to grow to a clinically meaningful size (Jonassen, Cooney et al. 1999). Morphological classification of the directional growth of calculi supported the necessity for a fixed point of origin, in the absence of obstruction (Hinman 1979). These observations suggested that most stones must initiate from a fixed point or nidus in the collecting system or renal papilla.