Identification of Novel Proteins Secreted by the Kidney

Yale University, New Haven CT

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Abstract

DESCRIPTION (provided by applicant): Hemodialysis therapy is a life saving procedure for patients with either chronic end-stage renal disease or acute renal failure. However, the morbidity and mortality associated with this therapy are undesirably high, and many patients suffer from a poor quality of life. The causes for these less than ideal results are not entirely clear. Since the procedure uses an extracorporeal "artificial kidney" to remove excess water and soluble wastes from the blood, it can't replicate the important absorptive, metabolic, endocrine, and immunological functions of the natural organ. Therefore, a very strong possibility is that the incomplete replacement of kidney functions contributes to the dismal prognosis of patients on dialysis. The importance of understanding the kidney's endocrine function is underscored by the discovery of erythropoietin. There is evidence to suggest that the kidney's endocrine function is not limited to the secretion of renin and erythropoietin. The characterization of previously unknown proteins/hormones that are secreted by the kidney will not only provide a more complete understanding of renal physiology but may also significantly improve the way we treat patients with end-stage renal disease. As a first step toward these endeavors, this proposal is aimed at identifying novel proteins that are secreted by the kidney using a human functional genomics database, coupled with an innovative approach for gene expression, which allows rapid analysis of many genes in parallel. In this proposal, we address three issues: 1) What are the novel candidate genes potentially encoding secreted proteins? 2) Are the candidate genes specifically or highly expressed in the kidney? 3) Do these candidate genes indeed encode secreted proteins?