This project concerns the molecules that inhibit formation of crystals in human kidneys. Males who form stones differ from normal males in producing urine less effective in slowing the growth of calcium oxalate crystals, and in which the distance between supersaturation and the supersaturation needed to produce crystallization (upper limit of metastability, ULM) is reduced for both calcium oxalate and calcium phosphate. A parallel study is proposed in women, to determine if their mechanisms of stones differ from those in men, and in family members of the male stone formers we have already characterized, to determine if reduced growth inhibition and ULM to supersaturation distance is familial. In collaboration with Project 2, we propose to determine if reduced inhibitions correlate with Randall's plaque number and surface area. Given the male growth inhibition defect, we propose to identify molecules responsible by pursuing our initial observation of aberrant calgranulin molecular size distribution and specific growth inhibition activity, and by contrasting proteins bound to calcium oxalate crystals brought to equivalent degrees of growth inhibition by patient and control dialyzed urine molecules. We will explore the possibility that crystallization in urine consumes high affinity inhibitors reducing their availability, by determining the effects of EDTA dissolution on growth inhibition by urine molecules. Finally, we plan similar experiments to identify molecules responsible for the reduced ULM to supersaturation distance by contrasting molecules from patients and normals bound to the calcium oxalate and calcium phosphate crystals produced as their urine supersaturation is raised above the ULM in vitro. We will also explore the possibility that reduced urine pyrophosphate or an abnormal relationship between urine citrate and urine pH may contribute to the reduced ULM in patients.
| 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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