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.

John C. Lieske, M.D., 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. As director of the O'Brien Urology Research Center, he leads Mayo Clinic researchers who investigate crucial unanswered questions in nephrolithiasis research, work to define the pathogenesis of nephrolithiasis, and seek to improve treatment and preventative strategies of chronic kidney disease.

Focus areas

Specific research topics include:

• Identifying cell surface receptor molecules for urinary crystals
• Identifying factors in tubular fluid that alter crystal adhesion to cells, including the apparently central role played by the Tamm-Horsfall protein
• Identifying the mechanisms by which injury increases crystal binding to cells
• Identifying mechanisms by which renal cells can promote crystal nucleation
• Developing animal models to study crystal retention that employ continuous oxalate infusion and genetically altered expression of receptor molecules
• Identifying the role that nanobacteria, a recently described calcified microorganism, may play in the formation of kidney stones and other calcifying disorders (such as atherosclerosis)
• In collaboration with colleagues in radiology and cardiology, developing more quantitative and sensitive methods to detect renal calcification
• Identifying genetic and environmental risk factors for renal stone formation using resources of the Rochester Epidemiology Project
• Establishing an international registry for inherited forms of calcium urolithiasis (Dent's disease and primary hyperoxaluria) in coordination with the Mayo Clinic Hyperoxaluria Center
• Evaluating novel methods to treat enteric hyperoxaluria, including the use of probiotics and herbal therapy

Significance to patient care

Kidney stones cause significant pain, loss of productivity and medical expense. In rarer cases, they can cause kidney damage and kidney failure.

Dr. Lieske's research is identifying underlying causes of kidney stones and improving treatment strategies to prevent these complications.