The earliest events in kidney stone formation remain poorly understood. It is known that fluid within renal tubules is often supersaturated favoring the formation of crystals. However, calculations based on the known rates of tubular fluid flow and crystal growth suggest that newly-formed crystals could never become large enough to block an individual tubule lumen. Therefore, crystals that develop in the nephron should be excreted in tubular fluid, and kidney stones should not form.

Since many individuals do form stones, other unknown factors must, in certain circumstances, permit retention of crystals in the kidney. Our laboratory is working to identify those factors that mediate adhesion of crystals to tubule lining cells and understand how subsequent cellular processing of retained crystals results in renal stone formation. Specific research topics include:

• Identify cell surface receptor molecules for urinary crystals.
• Identify factors in tubualr fluid that alter crystal adhesion to cells, includign the apparently cnetral role that Tamm Horsfall plays.
• Identify the mechanisms whereby injury increases crystal binding to cells.
• Identify mechanisms whereby renal cells can promote crystal nucleation.
• Develop animal models to study crystal retention that employ continuous oxalate infusion and genetically altered expression of receptor molecules.
• Identify the role that nanobacteria, a recently-described calcified microorganism, may play in the formation of kidney stones and other calcifying disorders (e.g., atherosclerosis).
• In collboration with colleagues in Radiology and Cardiology, develop more quantitative and sensative methods to detect renal calcification.
• Identify genetic and environmental risk factors for renal stone formation using resources of the Rochester Epidemiology Project.
• Establish an international registry for inhertited forms of calcium urolithiaisis (Dent's Disease and Primary hyperoxaluria), in coordination with the Mayo Clinic Hyperoxaluria Center.
• Evaluate novel methods to treat enteric hyperoxaluria, including use of probiotics and herbal therapy.