Background: Feline nephroliths pose an imminent threat of ureteral obstruction and acute kidney injury. Some nephroliths form over papillary mineralization. Papillary mineral that is exposed to the urinary space provides a preformed surface for heterogeneous nucleation at levels below oversaturation. This mechanism of stone formation might not be effectively prevented by strategies that reduce urine saturation. Understanding the causes of renal parenchymal mineralization might unveil new treatment targets to prevent stone formation and preserve renal function. Hypothesis/
Objectives: Besides oversaturation of calcium salts, feline renal mineralization is associated with expression of an osteogenic phenotype. Samples: Eighteen kidneys with medullary mineralization (10 with and 8 without nephroliths) were obtained from 18 cats undergoing necropsy.
Methods: To determine if osteogenic proteins co-localize with papillary mineralization, tissue sections were examined using immunohistochemistry for five osteogenic markers (osteopontin, osteocalcin, bone morphogenic protein-2, runt-related transcription factor-2, and tissue non-specific alkaline phosphatase) and minerals (Von Kossa).
Results: Osteopontin and osteocalcin co-localized with mineral deposits in 18 and 12 kidneys, respectively. Co-localization of other osteogenic proteins and minerals were found in two or fewer kidneys. There were no differences in co-localization of osteogenic protein expression and mineralization between the kidneys with and without nephroliths. Conclusions and Clinical Importance: These results provide evidence that cell-mediated osteogenic-like processes might contribute to renal mineralization in cats. Targeting these processes could offer a new approach to prevent kidney stone formation at its origin.
