Hyperoxaluria is reduced and nephrocalcinosis prevented with an oxalate-degrading enzyme in mice with hyperoxaluria.
| Autor: | Grujic D; Altus Pharmaceuticals, 625 Putnam Avenue, Cambridge, MA 02139, USA. dgrujic@altus.com, Salido EC, Shenoy BC, Langman CB, McGrath ME, Patel RJ, Rashid A, Mandapati S, Jung CW, Margolin AL |
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| Jazyk: | angličtina |
| Zdroj: | American journal of nephrology [Am J Nephrol] 2009; Vol. 29 (2), pp. 86-93. Date of Electronic Publication: 2008 Aug 12. |
| DOI: | 10.1159/000151395 |
| Abstrakt: | Background/aims: Hyperoxaluria is a major risk factor for recurrent urolithiasis and nephrocalcinosis. We tested an oral therapy with a crystalline, cross-linked formulation of oxalate-decarboxylase (OxDc-CLEC) on the reduction of urinary oxalate and decrease in the severity of kidney injury in two models: AGT1 knockout mice (AGT1KO) in which hyperoxaluria is the result of an Agxt gene deficiency, and in AGT1KO mice challenged with ethylene glycol (EG). Methods: Four different doses of OxDc-CLEC mixed with the food, or placebo were given to AGT1KO mice (200 mg/day, n = 7) for 16 days and to EG-AGT1KO mice (5, 25, and 80 mg, n = 11) for 32 days. Results: Oral therapy with 200 mg OxDc-CLEC reduced both urinary (44%) and fecal oxalate (72%) in AGT1KO mice when compared to controls. Similarly, in EG-AGT1KO mice, each of the three doses of OxDc-CLEC produced a 30-50% reduction in hyperoxaluria. A sustained urinary oxalate reduction of 40% or more in the 80 mg group led to 100% animal survival and complete prevention of nephrocalcinosis and urolithiasis. Conclusion: These data suggest that oral therapy with OxDc-CLEC may reduce hyperoxaluria, prevent calcium oxalate nephrocalcinosis and urolithiasis, and can represent a realistic option for the treatment of human hyperoxaluria, independent of cause. (Copyright (c) 2008 S. Karger AG, Basel.) |
| Databáze: | MEDLINE |
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