College of Veterinary Medicine
Understanding formation of pathologic mineralization in the kidney is crucial for developing effective therapeutic strategies for two common and often fatal diseases in cats, calcium oxalate (CaOx) nephroureteroliths and chronic kidney disease (CKD). Unfortunately, by the time cats are diagnosed, these diseases are typically irreversible. Although research has shown that contemporary therapies successfully slow progression, the prevalence of CaOx uroliths and CKD continue to rise. This may occur because kidney mineralization is associated with greater interstitial fibrosis and interstitial inflammation than those without mineralization. Forty-seven percent of cats with CKD develop CaOx nephroliths. To improve care for these cats, it is necessary to prevent mineralization before interstitial inflammation and nephrolithiasis irreversibly damage kidneys. To do this, several important questions need answers:
- What mechanisms underlie tissue mineralization and urolith formation?
- Where does the mineralization process start?
- Are these two diseases, CKD and CaOx urolith formation, interrelated through similar mechanisms of mineralization?
These researchers hypothesize that kidney mineralization is not merely a passive process due to increasing concentrations of mineral precursors, but involves an active process where kidney cells are recruited to develop osteogenic traits. This study is designed to perform detailed ultra-structural evaluations (histopathology, micro computerized X-ray tomography, scanning electron microscopy, energy-dispersive X-ray spectrometry, and infra-red spectroscopy) of kidneys and their nephroliths. Immunohistochemistry will be used to localize osteogenic proteins in kidneys. If the hypothesis is correct, novel therapies designed to minimize mineralization associated CKD and CaOx uroliths will improve patient survival.