Abstract

Oxalate, an end product of metabolism, is a major component of 80% of kidney stones, and small changes in its urinary concentration critically influence calcium oxalate crystallization. The high frequency of a family history in """"""""idiopathic"""""""" renal stone disease has suggested to some investigators that urolithiasis may be a metabolic disorder characterized by a defect in cellular oxalate transport. Inherited defects in erythrocyte calcium and oxalate transport have been recently identified in patients with kidney stones, strengthening the contention that abnormalities in cellular transport may play a primary role in """"""""idiopathic"""""""" calcium stone formation. However, the cellular transport of oxalate has not been characterized in the kidney, particularly in papillary cells where calcium oxalate crystallization usually occurs.
The aims of this proposal, thus are; 1. To characterize oxalate transport in renal cortical and papillary cells. 2. To assess alterations in oxalate handling in experimental models of nephrolithiasis that feature nephron dysfunction or injury. These studies will help elucidate the role of nephron dysfunction or injury in the pathogenesis of calcium oxalate nephrololithiasis and may give us insights on how to prevent this disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK043184-01
Application #
3244497
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1991-01-01
Project End
1994-12-31
Budget Start
1991-01-01
Budget End
1991-12-31
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
University of Massachusetts Medical School Worcester
Department
Type
Schools of Medicine
DUNS #
660735098
City
Worcester
State
MA
Country
United States
Zip Code
01655

  Publications

Jonassen, Julie A; Kohjimoto, Yasuo; Scheid, Cheryl R et al. (2005) Oxalate toxicity in renal cells. Urol Res 33:329-39
Cao, Lu-Cheng; Honeyman, Thomas W; Cooney, Rachel et al. (2004) Mitochondrial dysfunction is a primary event in renal cell oxalate toxicity. Kidney Int 66:1890-900
Scheid, Cheryl R; Cao, Lu-Cheng; Honeyman, Thomas et al. (2004) How elevated oxalate can promote kidney stone disease: changes at the surface and in the cytosol of renal cells that promote crystal adherence and growth. Front Biosci 9:797-808
Jonassen, Julie A; Cao, Lu-Cheng; Honeyman, Thomas et al. (2003) Mechanisms mediating oxalate-induced alterations in renal cell functions. Crit Rev Eukaryot Gene Expr 13:55-72
Cao, L C; Jonassen, J; Honeyman, T W et al. (2001) Oxalate-induced redistribution of phosphatidylserine in renal epithelial cells: implications for kidney stone disease. Am J Nephrol 21:69-77
Zhao, G; Monier-Faugere, M C; Langub, M C et al. (2000) Targeted overexpression of insulin-like growth factor I to osteoblasts of transgenic mice: increased trabecular bone volume without increased osteoblast proliferation. Endocrinology 141:2674-82
Cao, L C; Honeyman, T; Jonassen, J et al. (2000) Oxalate-induced ceramide accumulation in Madin-Darby canine kidney and LLC-PK1 cells. Kidney Int 57:2403-11
Scheid, C; Honeyman, T; Kohjimoto, Y et al. (2000) Oxalate-induced changes in renal epithelial cell function: role in stone disease. Mol Urol 4:371-82
Miller, C; Kennington, L; Cooney, R et al. (2000) Oxalate toxicity in renal epithelial cells: characteristics of apoptosis and necrosis. Toxicol Appl Pharmacol 162:132-41
Kohjimoto, Y; Honeyman, T W; Jonassen, J et al. (2000) Phospholipase A2 mediates immediate early genes in cultured renal epithelial cells: possible role of lysophospholipid. Kidney Int 58:638-46

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