KIDNEY STONE INHIBITORS

DESCRIPTION (provided by applicant): Urolithiasis is a worldwide problem. The lifetime prevalence of urolithiasis is 13% for men and 7% for women in the U.S (NIDDK) and an estimated 2.1 billion was spent in claims for diagnosis for urolithiasis in 2000 which was 50% more than 1994 (Pearle, 2005). Up to 50% of patients may have recurrence within 5 years. (Asplin et al., 1996). Stones injure kidneys, cause infection and obstruction and many patients suffer from pain of stone passage, urinary infection and bleeding (Chow etal.,2004).The recurrence of stones after treatment is normally controlled by diet and/or oral medications that reduce urinary concentrations of calcium such as thiazides and/or potassium citrate. Current dosages for these medications are very high and could cause serious side effects, gastrointestinal lesions, nausea and other complications resulting in poor compliance. Such small inhibitor molecules in high doses alter only the rate of stone formation. Our proposed materials are designed forthe direct inhibition of crystal formation at extremely low doses via multisite adsorptive inhibition. The proposed compounds are anticipated to have the ability at the molecular level to penetrate the barriers and achieve glomerular concentrations. Thereis a dire need for such effective potent inhibitors for stone prevention management and infection control. The innovation that we present is the incorporation of some key features in a single potent inhibitor molecule -adsorptive inhibition of insolublestone forming calcium compounds and potential reduction of protein adsorption due to their hydrophilic properties. The toxicological properties of the proposed compounds are anticipated to be favorable for human use. Dr.Jeff Wesson M.D, Nephrologist, at the medical College of Wisconsin, a well known authority in this area of will serve as an advisor for in vitro testing that will be conducted at IET and University of Buffalo, SUNY chemical engineering dept. We hope to establish the significant inhibitory effect of our inhibitor compounds on CaOx nucleation, growth kinetics, aggregation, morphology and composition as a function of concentration and type of the inhibitors. In vitro toxicity will be evaluated using accepted kidney epithelial cell lines. Medicalprevention of Nephrolithiasis is justified on a cost saving basis quite apart from its benefits to patients in tems of reduced morbidity and risk from surgical procedures, obstruction, and infection (Parks et al., 1996). PUBLIC HEALTH RELEVANCEPUBLIC HEALTH RELEVANCE: Over 2million stone removal procedures are done in the US for kidney stones. The cost of treatment could be approximated to 2000/procedure bringing the total to 4 billion dollars in addition to the expenses on diagnosis etc. Themedical treatment is believed to be at least 1/4th, bringing savings to the health care system.