There is evidence of histopathology and tissue damage to virtually all segments of the nephron in patients with Sickle Cell Anemia (SSA). The goal of the proposed studies is to provide information about 1) the pathophysiology of the glomerulopathy that occurs in SSA patients; and 2) to determine the pattern of changes in renal function. The mechanism for defective urine concentrating ability is attributed to ischemic tissue damage from obstruction of blood vessels by sickled erythrocytes. However, there is no generally accepted explanation for the pathophysiology of glomerulopathy even though this is a prominent cause of chronic renal failure in SSA patients. Initially, SSA patients exhibit an increase in GFR but the course of progressive loss of renal function has not been documented. We propose to obtain information about the physiological changes in glomerular function associated with proteinuria in SSA patients using the dextran-sieving technique coupled with measurements of GFR, renal blood flow, and plasma hormones. We will analyze the determinants of GFR as well as evaluate the size and distribution of pores penetrating the glomerular basement membrane. Four groups will be studied: Group A with no proteinuria or evidence of renal insufficiency; Group B with proteinuria but without renal insufficiency; Group C with proteinuria and mild to moderate renal insufficiency; and Group D, healthy controls. In addition to comparisons between groups, a longitudinal study of Groups B & C will be used to determine the pattern of changes in renal function. It is hoped that the results will provide information permitting the rational development of preventive or therapeutic trials.
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