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.
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.
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 : |
Kittanamongkolchai, Wonngarm; Vaughan, Lisa E; Enders, Felicity T et al. (2018) The Changing Incidence and Presentation of Urinary Stones Over 3 Decades. Mayo Clin Proc 93:291-299 |
Dhondup, Tsering; Kittanamongkolchai, Wonngarm; Vaughan, Lisa E et al. (2018) Risk of ESRD and Mortality in Kidney and Bladder Stone Formers. Am J Kidney Dis 72:790-797 |
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 |
Showing the most recent 10 out of 100 publications