This program project grant concerns mechanisms of idiopathic calcium oxalate stone formation. The general premise is that mammalian kidneys have evolved defenses against crystallization because they must conserve water yet excrete obligatory loads of calcium salts that produce inevitable supersaturations. In normal humans and humans who form stones, one project focuses on defining urine molecules that defend against growth, nucleation, aggregation, and renal cell adhesion of calcium oxalate and obtained by biopsy of renal papillae to characterize microscopic anatomy, crystal structure, and clinical and metabolic correlates of Randall's plaques, which are thought to be a precursor to anchored papillary stones. For over 10 years we have bred and studied a strain of hypercalciuric stone forming rats, whose hypercalciuria arises from an excess of the vitamin D receptor. Our third project focuses on these animals. Because their stones and plaques advance with age, the sequence advance with age, the sequence of anatomical events, especially initial sites of crystallization can be studied. The relationship between urine supersaturations and crystal inhibition in relation to stones affords an easily manipulated in vivo model of stone formation and their. The rat vitamin D vector defect offers continued opportunity for understanding regulation of that hormone system. Rat and human studies are proposed in our fourth project to test definitely the hypothesis that an excess of vitamin D receptor in the duodenum causes some forms of human hypercalciuria. Other aspects of the project concern the receptor in bone and parathyroid cells, and the role of cytokines in mediating bone mineral loss in hypercalciuria. Studies of cultured renal epithelial cells in our final project complement and amplify the work with human and rat tissue and Randall's plaques, offering detailed understanding of how cells react to crystals, anchor and ingest them.
| Williams Jr, James C; Borofsky, Michael S; Bledsoe, Sharon B et al. (2018) Papillary Ductal Plugging is a Mechanism for Early Stone Retention in Brushite Stone Disease. J Urol 199:186-192 |
| Worcester, Elaine M; Bergsland, Kristin J; Gillen, Daniel L et al. (2018) Mechanism for higher urine pH in normal women compared with men. Am J Physiol Renal Physiol 314:F623-F629 |
| Bergsland, Kristin J; Coe, Fredric L; Parks, Joan H et al. (2018) Evidence for a role of PDZ domain-containing proteins to mediate hypophosphatemia in calcium stone formers. Nephrol Dial Transplant 33:759-770 |
| Kleinguetl, Colin; Williams Jr, James C; Ibrahim, Samar A et al. (2017) Calcium Tartrate Tetrahydrate, Case Report of a Novel Human Kidney Stone. J Endourol Case Rep 3:192-195 |
| Mulay, Shrikant R; Eberhard, Jonathan N; Desai, Jyaysi et al. (2017) Hyperoxaluria Requires TNF Receptors to Initiate Crystal Adhesion and Kidney Stone Disease. J Am Soc Nephrol 28:761-768 |
| Winfree, Seth; Khan, Shehnaz; Micanovic, Radmila et al. (2017) Quantitative Three-Dimensional Tissue Cytometry to Study Kidney Tissue and Resident Immune Cells. J Am Soc Nephrol 28:2108-2118 |
| Borofsky, Michael S; Dauw, Casey A; York, Nadya et al. (2017) Accuracy of daily fluid intake measurements using a ""smart"" water bottle. Urolithiasis : |
| Winfree, Seth; Ferkowicz, Michael J; Dagher, Pierre C et al. (2017) Large-scale 3-dimensional quantitative imaging of tissues: state-of-the-art and translational implications. Transl Res 189:1-12 |
| Cohen, Andrew J; Borofsky, Michael S; Anderson, Blake B et al. (2017) Endoscopic Evidence That Randall's Plaque is Associated with Surface Erosion of the Renal Papilla. J Endourol 31:85-90 |
| Gilad, Ron; Williams Jr, James C; Usman, Kalba D et al. (2017) Interpreting the results of chemical stone analysis in the era of modern stone analysis techniques. J Nephrol 30:135-140 |
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