Urologic stones are a common cause of upper urinary tract obstruction and a major source of morbidity in humans. Available clinical evidence suggests that the initial stone forms within the pelvic recesses, but the mechanisms involved in this process are poorly understood. The pelvic recesses are anatomically conducive to urinary stasis and are lined by a simple cuboidal epithelium that is continuous with the epithelium covering the renal papilla.
The specific aims of the present proposal are to study the transport of calcium, oxalate, citrate, and phosphate (ions known to be principally involved in clinical calcium oxalate stone formation) across the papillary surface epithelium (PSE). Rabbit PSE will be isolated and mounted in a modified Ussing chamber to study transepithelial transport. It is hypothesized that the composition of fluid within the pelvic recesses is modified by transport of crystal components and inhibitors across the PSE, which in turn will alter the physio-chemical factors of crystallization that dictate the rate of stone nucleation and growth. To integrate the information obtained from PSE transport experiments and the Supersaturation theory of crystal formation, a mathematical model will also be developed that is based on the conservation of mass, electroneutrality, and ionic strength within the pelvic recesses. Understanding the nature of the anatomical sites and mechanisms of initial stone formation within the renal pelvis is fundamental to our understanding of urolithiasis and in determining subsequent therapeutic intervention. The proposed work will enhance our understanding of how initial calcium oxalate stone formation occurs within the mammalian renal pelvis.
|Chandhoke, P S; Fan, J (2000) Transport of oxalate across the rabbit papillary surface epithelium. J Urol 164:1724-8|
|Chandhoke, P S; Fan, J; May, D J et al. (1999) Role of the renal collecting system in initial kidney stone formation. J Endourol 13:601-4|
|Fan, J; Chandhoke, P S; Grampsas, S A (1999) Role of sex hormones in experimental calcium oxalate nephrolithiasis. J Am Soc Nephrol 10 Suppl 14:S376-80|