In the United States, renal stone disease accounts for 7 to 10 out of every 1,000 hospital admissions and 1 of 1,000 individuals are afflicted with stone disease during their lifetime. Approximately 80% of all stones contain calcium oxalate, and uric acid and struvite accounts for about 10-15%. It is well accepted that an important event in stone initiation is the heterogeneous nucleation of stone crystals, and that matrix serves as one of the major sources of organic nucleation materials. Of special interest are the acidic phospholipids which are present in the urine probably as the result of cellular injury, sloughing of the damaged cells into the urine, cell death, and the release of membrane components into the urine. Following the theories expressed in the bone growth field, and the fact that calcium phosphate in the form of apatite is frequently found as the nidus in calcium oxalate stones, the application hypothesizes that acidic phospholipids derived from the renal tubule plasma membrane form a complex with calcium and inorganic phosphate which then orders and becomes apatite. The principal investigator and his colleagues have been the only research group to explore this possibility in stone disease. This is an important subject and definitely requires further investigation. The main goal of the proposed research is to investigate the presence of lipids in calcium oxalate, struvite, and uric acid stones, identify the individual lipids and determine their role in the nucleation of calcium oxalate crystals in vitro. The experimental plan will compare the lipid composition determined in these stones with the lipid composition found in renal epithelial plasma membranes. The hypothesis in these studies is that calcium oxalate stones will contain phospholipids, uric acid stones will contain less phospholipid content, and struvite stones (which are formed in the presence of ammonia-splitting bacteria) will contain both complexed glycolipids as well as phospholipids.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK041434-01A2
Application #
3242185
Study Section
General Medicine B Study Section (GMB)
Project Start
1991-01-01
Project End
1995-12-31
Budget Start
1991-01-01
Budget End
1991-12-31
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Florida
Department
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Khan, Saeed R (2002) Stone research on the bench: where we are and where we are going. J Endourol 16:413-6
Khan, Saeed R; Glenton, Patricia A; Backov, Renal et al. (2002) Presence of lipids in urine, crystals and stones: implications for the formation of kidney stones. Kidney Int 62:2062-72
Fasano, J M; Khan, S R (2001) Intratubular crystallization of calcium oxalate in the presence of membrane vesicles: an in vitro study. Kidney Int 59:169-78
Gokhale, J A; Glenton, P A; Khan, S R (2001) Characterization of Tamm-Horsfall protein in a rat nephrolithiasis model. J Urol 166:1492-7
Moriyama, M T; Glenton, P A; Khan, S R (2001) Expression of inter-alpha inhibitor related proteins in kidneys and urine of hyperoxaluric rats. J Urol 165:1687-92
Khan, S R; Maslamani, S A; Atmani, F et al. (2000) Membranes and their constituents as promoters of calcium oxalate crystal formation in human urine. Calcif Tissue Int 66:90-6
Khan, S R; Thamilselvan, S (2000) Nephrolithiasis: a consequence of renal epithelial cell exposure to oxalate and calcium oxalate crystals. Mol Urol 4:305-12
Thamilselvan, S; Byer, K J; Hackett, R L et al. (2000) Free radical scavengers, catalase and superoxide dismutase provide protection from oxalate-associated injury to LLC-PK1 and MDCK cells. J Urol 164:224-9
Maslamani, S; Glenton, P A; Khan, S R (2000) Changes in urine macromolecular composition during processing. J Urol 164:230-6
Thamilselvan, S; Hackett, R L; Khan, S R (1999) Cells of proximal and distal tubular origin respond differently to challenges of oxalate and calcium oxalate crystals. J Am Soc Nephrol 10 Suppl 14:S452-6

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