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.
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
|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 :|
|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|
Showing the most recent 10 out of 100 publications