1964 OF MICE AND MEN: MALE GENDER, HYPEROXALURIA AND HYPERCALCIURIA PROMOTE CALCIUM OXALATE STONE FORMATION IN MICE

Abstract

You have accessJournal of UrologyStone Disease: Basic Research1 Apr 20101964 OF MICE AND MEN: MALE GENDER, HYPEROXALURIA AND HYPERCALCIURIA PROMOTE CALCIUM OXALATE STONE FORMATION IN MICE Saeed Khan and Benjamin Canales Saeed KhanSaeed Khan More articles by this author and Benjamin CanalesBenjamin Canales More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1974AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Despite years of sustained research, the pathophysiology of idiopathic CaOx stone disease is still poorly understood. The availability of various genetically engineered transgenic and knock out (KO) mice provides an opportunity to advance our knowledge in this regard. It has however proven difficult to produce CaOx stones in mice by inducing hyperoxaluria alone. We hypothesized that CaOx nephrolithiasis in mice requires an increase in the urinary excretion of both calcium and oxalate. To investigate it further and develop a dependable mouse model of CaOx stone formation, we tested whether hyperoxaluria inducing agents that have proven successful in rats could induce CaOx stones in the normocalciuric and hypercalciuric mice. METHODS Four to six month old male and female normocalciuric B6 wild type (WT) and hypercalciuric Npt2a KO mice weighing 18-30 gm were given 1.25% ethylene glycol (EG), or 1.5% glyoxylate (Gox). 24-hour urine samples were collected on days 0, 3, 7, 14, 21 and 28 and their pH measured. Urine was analyzed for crystalluria and calcium and oxalate. Mice were sacrificed on day 28, using carbon dioxide. RESULTS Npt2a KO mice are hypercalciuric and produce calcium phosphate deposits in their kidneys. By day 7 of receiving hyperoxaluria inducing diets, all mice, normocalciuric B6 and hypercalciuric KO mice, male and female became hyperoxaluric and showed CaOx crystalluria. There were no identifiable crystal deposits in the kidneys of any B6 mice, on hyperoxaluric or regular diet. On the other hand, only the male hypercalciuric Npt2a KO mice, receiving Gox or EG, developed CaOx crystal deposits, and only after 28 days of treatment. Kidneys of all mice on hyperoxaluria inducing diets, with or without renal CaOx crystals showed signs of injury and inflammation. Vacuolar degeneration of the tubules was common and inflammatory cells were visible in the cortical interstitium. Male mice showed more injury than the female mice. CONCLUSIONS Results indicate that CaOx stone formation can be induced in the mice. As is the case in the humans, male gender, hyperoxaluria, and hypercalciuria are risk factors for CaOx stone formation in mice. High oxalate even in the absence of renal crystal deposits is injurious to the renal epithelium. Gainesville, FL© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e763 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Saeed Khan More articles by this author Benjamin Canales More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...