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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54DK100227-02
Application #
8734910
Study Section
Special Emphasis Panel (ZDK1-GRB-9)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
2
Fiscal Year
2014
Total Cost
$96,090
Indirect Cost
$35,454
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Ferrero, A; Gutjahr, R; Henning, A et al. (2017) Renal Stone Characterization using High Resolution Imaging Mode on a Photon Counting Detector CT System. Proc SPIE Int Soc Opt Eng 10132:
Huang, Alice E; Montoya, Juan C; Shiung, Maria et al. (2017) Consistency of Renal Stone Volume Measurements Across CT Scanner Model and Reconstruction Algorithm Configurations. AJR Am J Roentgenol 209:116-121
Perinpam, Majuran; Enders, Felicity T; Mara, Kristin C et al. (2017) Plasma oxalate in relation to eGFR in patients with primary hyperoxaluria, enteric hyperoxaluria and urinary stone disease. Clin Biochem 50:1014-1019
Rossano, Adam J; Romero, Michael F (2017) Optical Quantification of Intracellular pH in Drosophila melanogaster Malpighian Tubule Epithelia with a Fluorescent Genetically-encoded pH Indicator. J Vis Exp :
Lieske, John C (2017) Probiotics for prevention of urinary stones. Ann Transl Med 5:29
Ferrero, Andrea; Chen, Baiyu; Li, Zhoubo et al. (2017) Technical Note: Insertion of digital lesions in the projection domain for dual-source, dual-energy CT. Med Phys 44:1655-1660
Pottel, Hans; Dubourg, Laurence; Schaeffner, Elke et al. (2017) Data on the relation between renal biomarkers and measured glomerular filtration rate. Data Brief 14:763-772
Kittanamongkolchai, Wonngarm; Mara, Kristin C; Mehta, Ramila A et al. (2017) Risk of Hypertension among First-Time Symptomatic Kidney Stone Formers. Clin J Am Soc Nephrol 12:476-482
Gutjahr, R; Polster, C; Henning, A et al. (2017) Dual Energy CT Kidney Stone Differentiation in Photon Counting Computed Tomography. Proc SPIE Int Soc Opt Eng 10132:
Canales, Benjamin K; Smith, Jennifer A; Weiner, I David et al. (2017) Polymorphisms in Renal Ammonia Metabolism Genes Correlate With 24-Hour Urine pH. Kidney Int Rep 2:1111-1121

Showing the most recent 10 out of 85 publications