Minipump Induced Hyperoxaluria and Crystal Deposition in Rats: A Model for Calcium Oxalate Urolithiasis

No AccessJournal of UrologyINVESTIGATIVE UROLOGY1 Mar 2004Minipump Induced Hyperoxaluria and Crystal Deposition in Rats: A Model for Calcium Oxalate Urolithiasis SUSAN RUTH MARENGO, DANIEL H.-C. CHEN, GREGORY T. MacLENNAN, MARTIN I. RESNICK, and GRETTA H. JACOBS SUSAN RUTH MARENGOSUSAN RUTH MARENGO More articles by this author , DANIEL H.-C. CHENDANIEL H.-C. CHEN More articles by this author , GREGORY T. MacLENNANGREGORY T. MacLENNAN More articles by this author , MARTIN I. RESNICKMARTIN I. RESNICK More articles by this author , and GRETTA H. JACOBSGRETTA H. JACOBS More articles by this author View All Author Informationhttps://doi.org/10.1097/01.ju.0000101046.39244.44AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Unraveling the mechanisms leading to clinically active calcium oxalate (CaOx) stone disease and the development of effective medical therapies to treat it have been hampered by the lack of appropriate animal models. To address this problem we developed a model of hyperoxaluria and calcium oxalate crystal deposition by implanting osmotic minipumps subcutaneously into male rats, that is minipump induced hyperoxaluria and crystal deposition in rats. Materials and Methods: Male Harlan-Sprague Dawley rats (225 to 290 gm) were implanted subcutaneously with 1-week 2 ml osmotic minipumps containing 1.5 M potassium oxalate (360 μM KOx/24 hours, [KOx-trt], 11) or phosphate buffered saline (PBS-trt, 9) on days 1 and 7. The 24-hour urine collections were performed on days 0, 4, 7, 11 and 14. Data were analyzed by ANOVA and Tukey’s HSD. Urinary crystals were analyzed by light microscopy. Kidneys were harvested on day 14 and processed for light and polarizing microscopy, and RNA analysis. Results: Mean overall creatinine excretion ± SEM (PBS-trt 107 ± 7 and KOx-trt 123 ± 6 μM/24 hours, p >0.07) and day 14 serum creatinine (PBS-trt 83 ± 4 and KOx-trt 83 ± 5 μM, p ≥0.9) were similar in the 2 treatment groups. Overall urinary volume (PBS-trt 11.3 ± 0.8 and KOx-trt 18.0 ± 1.5 ml/24 hours, p ≤0.001) and oxalate (OX) excretion (PBS-trt 9.2 ± 0.6 and KOx-trt 44 ± 4.2 μM/24 hours, p ≤0.001) were higher in KOx-trt vs PBS-trt rats. In KOx-trt rats OX excretion on day 0 was significantly less than on any day after implantation (p ≤0.01). All KOx-trt rats excreted calcium oxalate dihydrate crystals by day 4 and had intrarenal deposits of birefringent crystals by day 14. Overall the morphology of kidneys of OX rats was normal, although localized regions of inflammation and tubular debris were occasionally observed. Reverse transcriptase-polymerase chain reaction and Northern blot analysis revealed that the expression of 3 distress molecules tumor necrosis factor receptor, osteopontin and kidney injury molecule were up-regulated in KOx-trt kidneys. Conclusions: The model of minipump induced hyperoxaluria and crystal deposition in rats reliably induces hyperoxaluria, CaOx crystalluria and CaOx crystal deposition. These characteristics make it an appropriate model for investigations of the effects of OX on renal physiology as well as investigating the efficacy of new therapeutics. References 1 : Relationship between experimentally induced crystalluria and relative supersaturation of various stone salts in rats. Urol Res1984; 12: 271. Google Scholar 2 : Experimental induction of crystalluria in rats using mini-osmotic pumps. Urol Res1983; 11: 199. 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Google Scholar From the Jim and Eilleen Dicke Research Laboratory, Department of Urology (SRM, DH-CC, MIR) and Institute of Pathology (GTM, GHJ) School of Medicine, Case Western Reserve University, Cleveland, Ohio© 2004 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 171Issue 3March 2004Page: 1304-1308 Advertisement Copyright & Permissions© 2004 by American Urological Association, Inc.Keywordsrats, Sprague-Dawleycalcium oxalatekidney calculikidneyMetricsAuthor Information SUSAN RUTH MARENGO More articles by this author DANIEL H.-C. CHEN More articles by this author GREGORY T. MacLENNAN More articles by this author MARTIN I. RESNICK More articles by this author GRETTA H. JACOBS More articles by this author Expand All Advertisement PDF downloadLoading ...