Individuals with
autosomal dominant polycystic kidney disease have a higher incidence of stone formation than the general population. However, there are no cystic animal models known to develop stones. Cystic mice compound heterozygous for hypomorphic Pkd1V and Pkd1RC alleles develop
cystic kidneys within a few weeks of birth but live beyond 20 wk of age, allowing for the study of cystic comorbidities including stone formation. Cystic Pkd1V/RC mice were euthanized at 3, 13, or 26 wk of age, and their kidneys were analyzed by microcomputed tomography (µCT) for stone formation. Mice had occasional
mineral aggregates that could be detected by µCT analysis at 3 wk of age. At 13 or 26 wk of age, numerous white masses were visible beneath the kidney surface. µCT analysis confirmed the masses to be large
mineral stone deposits throughout the renal cortex, with
mineral content increasing with age. Staining of histological sections with
alizarin red and von Kossa suggested that the stone deposits were composed primarily of
calcium and
phosphate. Microdissection confirmed stones localized within
cyst lumens. Analysis of individual stones by µCT and infrared spectroscopy confirmed
apatite mineral composition. Urinalysis revealed elevated levels of
phosphate and
citrate at 3 wk of age and lower pH and elevated levels of
calcium and
citrate at 13 wk of age, suggesting altered
phosphate and
calcium homeostasis as a potential cause of mineralization and renal stone formation. This is the first animal model exhibiting overt
kidney stone formation in the context of
cystic kidney disease.NEW & NOTEWORTHY Compound heterozygous Pkd1V/RC mice were found to form
calcium phosphate-containing stones within
cysts of the renal cortex by 13 wk of age. This is the first
polycystic kidney disease animal model exhibiting spontaneous stone formation. A growing body of evidence suggests a link between renal stone formation and
cystic kidney disease. This mouse model may be useful for studying the interplay between stone and
cyst formation and the functional role of
polycystins in
mineral homeostasis.