Nephrolithiasis (NL) is common, and symptomatic stone episodes cause significant pain, suffering, and economic cost. Much effort has been expended to define metabolic abnormalities that increase urinary supersaturation (SS), and thereby favor stone growth. However, currently available treatments that reduce urinary SS are not completely effective. Therefore, new understanding of additional pathogenic factors is needed to suggest new preventative strategies. Recent studies highlight the importance of NL precursor lesions, including Randall's plaques and plugs within distal tubular lumens. Qur preliminary data suggest that a subset of so-called """"""""idiopathic"""""""" CaOx stones may also begin from tubular plugs. Clinical kidney stone research has lagged because stone passage is the final result of many earlier events, and this series of events likely differs between apparently similar patients. Contributors to urinary SS (e.g. calcium excretion) are clearly important, but other factors such as cellular responses to SS and crystals or protein crystallization inhibitors also contribute to stone formation. We hypothesize that clinical studies to investigate stone pathogenesis have likely been confounded by the (unknown) variety of underlying renal pathologies. Therefore, we plan to carefully phenotype renal stone precursor lesions by direct endoscopic visualization. These carefully pheontyped patients will be used to develop imaging algorithms to noninvasively characterize stone composition and precursor lesions, to define the gene expression of papillary tissue of patients with and without plaque, and determine the urine and stone microbiome of diverse patient types.
Specific Aims are:
Aim 1 Accurately map kidney stone location and precursor lesions after percutaneous nephrolithotomy in defined groups of patients with idiopathic CaQx stones (n=220), enteric hyperoxaluria (n=15), primary hyperoxaluria (n=5);uric acid stones (n=20);CaP stones (n=30), cystine stones (n=5), and controls without stones (n=30) Aim 2: Define dual energy CT algorithms to predict stone fragility Aim 3: Determine the gene expression profile of papillary tip biopsies with maximal and minimal plaque and plugs.
Aim 4 : Characterize the microbiome of urine and kidney stones of patients with diverse types of stones.
These aims build upon the preliminary data assembled by our multidisciplinary group over the last 4 years.

Public Health Relevance

Our studies and others have highlighted the diverse array of renal pathologies that can be present in similar types of stone patients. New knowledge regarding the precise pathogenic pathways that can lead to stones is required in order to identify susceptible patients and to develop alternative strategies to prevent stones. These advances will eliminate the personal burden of stone disease including pain, infection, lost productivity, and costs associated with treatment.

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
Franz, Marie C; Pujol-Giménez, Jonai; Montalbetti, Nicolas et al. (2018) Reassessment of the Transport Mechanism of the Human Zinc Transporter SLC39A2. Biochemistry 57:3976-3986
Lieske, John C (2018) Bariatric Surgery and Kidney Health. J Am Soc Nephrol 29:1085-1086
Moen, Taylor; Ferrero, Andrea; McCollough, Cynthia (2018) Robustness of Textural Features to Predict Stone Fragility Across Computed Tomography Acquisition and Reconstruction Parameters. Acad Radiol :
Abd El-Salam, Mohamed; Bastos, Jairo Kenupp; Han, Jing Jing et al. (2018) The Synthesized Plant Metabolite 3,4,5-Tri-O-Galloylquinic Acid Methyl Ester Inhibits Calcium Oxalate Crystal Growth in a Drosophila Model, Downregulates Renal Cell Surface Annexin A1 Expression, and Decreases Crystal Adhesion to Cells. J Med Chem 61:1609-1621
Sivaguru, Mayandi; Saw, Jessica J; Williams Jr, James C et al. (2018) Geobiology reveals how human kidney stones dissolve in vivo. Sci Rep 8:13731
Shah, Ronak Jagdeep; Lieske, John C (2018) Inching toward a Greater Understanding of Genetic Hypercalciuria: The Role of Claudins. Clin J Am Soc Nephrol 13:1460-1462
Ruetten, Hannah; Wegner, Kyle A; Romero, Michael F et al. (2018) Prostatic collagen architecture in neutered and intact canines. Prostate 78:839-848
Marcus, Roy P; Fletcher, Joel G; Ferrero, Andrea et al. (2018) Detection and Characterization of Renal Stones by Using Photon-Counting-based CT. Radiology 289:436-442
Ferrero, Andrea; Gutjahr, Ralf; Halaweish, Ahmed F et al. (2018) Characterization of Urinary Stone Composition by Use of Whole-body, Photon-counting Detector CT. Acad Radiol 25:1270-1276
Vaughan, Lisa E; Enders, Felicity T; Lieske, John C et al. (2018) Predictors of Symptomatic Kidney Stone Recurrence After the First and Subsequent Episodes. Mayo Clin Proc :

Showing the most recent 10 out of 100 publications