LIPIDS AND UROLITHIASIS

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DESCRIPTION (Adapted from the Applicant's Abstract): 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.