Kidney stones afflict about 1 in 11 Americans and the most common stones are composed of calcium oxalate (CaOx), but no therapies exist to treat CaOx kidney stone formation at its earliest stages. Recent evidence strongly suggests that patients who retain stones in their kidneys during the earliest phase of stone growth solely via the mechanism of Randall's (interstitial) plaque (RP) have a fundamentally different pathology of early stone growth than do those patients who retain stones in the kidney via other mechanisms. In spite of how common this pathway seems to be, the mechanism by which early stone growth proceeds on RP?and how this form of early stone growth may be different from other mechanisms?is not understood well enough to direct therapies toward blocking the growth of early stones in this most-common of CaOx patients. The overall objective for the present proposal is to map the mineral and protein transitions as CaOx stones initiate on Randall's plaque. The work proposed here is foundational for learning how to block the genesis of these stones, and thus to provide treatment to prevent stones from forming on Randall's plaques.

Public Health Relevance

Kidney stones afflict about 1 in 11 Americans and the most common stones are composed of a mineral called calcium oxalate, but no therapies exist to treat calcium oxalate kidney stone formation at its earliest stages. Many patients retain stones in their kidneys during the earliest phase of stone growth solely via growth onto kidney calcifications called Randall's plaque. We will learn the details of how calcium oxalate stones begin their growth onto Randall's plaque, with the goal of developing therapies to prevent this earliest stage of stone growth in this type of stone former.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK124776-01
Application #
9945857
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Kirkali, Ziya
Project Start
2020-05-01
Project End
2023-03-31
Budget Start
2020-05-01
Budget End
2021-03-31
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202