Obstruction of the urinary tract is a common clinical entity. Although clinical studies have revealed which functions of the kidney are affected and how much recovery can be expected, detailed insight into the mechanisms by which obstruction affects renal function has come mainly from studies in experimental animals. Cellular infiltration of the renal interstitium is a feature of a number of kidney diseases and may be a prominent histological manifestation in a number of entities leading to chronic renal failure. Urinary tract obstruction is a frequent cause of interstitial nephritis in humans. Experimental hydronephrosis is also associated with an increased number of cells in the renal cortical interstitium. The proposed studies will characterize the nature of the cellular infiltrate that occurs in the renal interstitium following acute unilateral or bilateral ureteral obstruction; examine the kinetics of clearance of immune cells from the kidney after the release of obstruction; correlate the kinetics of arrival and clearance of immune cells from the kidney with functional parameters including renal plasma flow, GFR and tubular function; determine the effects of changes in dietary protein intake prior to obstruction on the kinetics of arrival and clearance of different immune cell types and on renal function after relief of obstruction; determine the effect of pharmacological and/or antibody-mediated interventions which delete all or specific cell types infiltrating the renal interstitium on the physiological response of the kidney to obstruction or its release; explore the deletion of specific leukocyte cell types on the function of the kidney either acutely or chronically. Finally, we will isolate immune cells present in the interstitium of obstructed or post- obstructed kidneys and characterize their state of activation and eventually will examine in cultures of tubular or glomerular cells the physiologic effects of addition of immune cells isolated from the interstitium of obstructed kidneys on such cells. The information to be obtained in the present studies will hopefully provide further insight concerning the pathogenesis of obstructive injury and may, therefore, help in the development of useful therapeutic interventions that may prevent damage and/or enhance recovery of renal function.
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