The objectives of this application are to determine the key environmental and genetic factors that lead to symptomatic recurrence among stone formers, as well as to validate asymptomatic stone formation and growth by CT scan as a surrogate for symptomatic recurrence. The central clinical hypothesis is that kidney stone recurrence can be predicted from clinical, laboratory, and radiographic measurements in the electronic health record (EHR). Our central mechanistic hypothesis is that genomic markers for kidney stones contribute to an increased risk of incident and recurrent stone events. In order to develop effective prevention strategies for kidney stone recurrence, we plan to objectively test our hypotheses with the following aims:
Specific Aim #1 : To develop a model to better predict symptomatic stone recurrence using clinical and laboratory information from the comprehensive (inpatient and outpatient) health records of 4680 chart validated symptomatic stone formers in the Olmsted County general population (1984 to 2016).
Specific Aim #2 : To determine if urine chemistries, blood serologies, and life-style factors can improve the prediction of symptomatic recurrence beyond the clinical and laboratory characteristics available in the EHR using 800 incident stone formers in our expanded prospective cohort (2009 to 2017).
Specific Aim #3 : To determine if models predicting symptomatic recurrence in Aims 1 or 2 also predict radiographic stone formation and growth among 300 incident stone formers in our current prospective cohort.
Specific Aim #4 : To sample stone formers from the general population to identify causative genes. A) Assemble a cohort of 1500 carefully validated and phenotyped incident kidney stone formers, plus 1500 controls for genetic analysis. Multiplex families will be a focus of this recruitment effort. B) Screen 400 validated incident symptomatic kidney stone formers for significant variants in 66 candidate genes for hypercalcuria, employing exon capture and next generation sequencing.

Public Health Relevance

Kidney stones are common, affecting 8% of the adult population. Besides pain (often described as the worst ever experienced), stones lead to costly surgical interventions, loss of work, and the long-term complication of kidney failure requiring dialysis or transplantation. Currently, physicians cannot identify which patients are at high risk of recurrence. Thus, there is a critical need to develop clinical prediction tools for recurrence

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZDK1-GRB-9)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Mayo Clinic, Rochester
United States
Zip Code
Tang, Xiaojing; Bergstralh, Eric J; Mehta, Ramila A et al. (2015) Nephrocalcinosis is a risk factor for kidney failure in primary hyperoxaluria. Kidney Int 87:623-31
Lieske, John C; Mehta, Ramila A; Milliner, Dawn S et al. (2015) Kidney stones are common after bariatric surgery. Kidney Int 87:839-45
Cabrero, Pablo; Terhzaz, Selim; Romero, Michael F et al. (2014) Chloride channels in stellate cells are essential for uniquely high secretion rates in neuropeptide-stimulated Drosophila diuresis. Proc Natl Acad Sci U S A 111:14301-6
Lieske, John C; Turner, Stephen T; Edeh, Samuel N et al. (2014) Heritability of urinary traits that contribute to nephrolithiasis. Clin J Am Soc Nephrol 9:943-50
Tang, Xiaojing; Lieske, John C (2014) Acute and chronic kidney injury in nephrolithiasis. Curr Opin Nephrol Hypertens 23:385-90
Rodgers, Allen; Gauvin, Daniel; Edeh, Samuel et al. (2014) Sulfate but not thiosulfate reduces calculated and measured urinary ionized calcium and supersaturation: implications for the treatment of calcium renal stones. PLoS One 9:e103602
Meeusen, Jeffrey W; Lieske, John C (2014) Looking for a better creatinine. Clin Chem 60:1036-9
Lieske, John C (2014) New insights regarding the interrelationship of obesity, diet, physical activity, and kidney stones. J Am Soc Nephrol 25:211-2
Singh, Prince; Knoedler, John J; Krambeck, Amy E et al. (2014) Thiazide diuretic prophylaxis for kidney stones and the risk of diabetes mellitus. J Urol 192:1700-4
Jepperson, Maria A; Ibrahim, El-Sayed H; Taylor, Abby et al. (2014) Accuracy and efficiency of determining urinary calculi composition using dual-energy computed tomography compared with Hounsfield unit measurements for practicing physicians. Urology 84:561-4

Showing the most recent 10 out of 11 publications