The mechanism of altered renal function following ureteral obstruction: The role of infiltrating leukocytes.

This thesis studied a rat model of acute and reversible ureteral obstruction in which there is no necrosis and in which renal functional abnormalities are transient. A leukocyte infiltrate was found to be one of the earliest responses of the kidney to ureteral obstruction, occurring within four hours of obstruction, with the peak response occurring at 12 hours. The leukocytes form distinctive rings around the tubules, particularly distal tubules. The leukocyte cell infiltrate consists predominantly of macrophages with a lesser number of T-lymphocytes mainly of the cytotoxic, suppressor cell subclass. The kinetics of the macrophage invasion temporally correlates with both the decline in glomerular filtration rate and enhanced thromboxane B2 excretion. In addition the infiltrate correlates with alterations in tubular function. Total body irradiation of rats prior to the onset of obstruction so as to prevent the leukocyte infiltrate in the kidney, both reduces thromboxane B2 excretion and significantly improves renal haemodynamics after release of 24 hours of obstruction. This implies that infiltrating leukocytes contribute to the decline in glomerular filtration rate and renal plasma flow seen after obstruction, possibly via the production of vasoactive prostanoids such as thromboxane A2. The elimination of the leukocyte infiltrate from the obstructed kidney, however, does not return the function of the post-obstructed kidney to normal. Glomeruli isolated from rats with ureteral obstruction demonstrate an enhanced ability to produce a variety of prostanoids, including thromboxane A2 and this also appears to play a role in the functional changes following ureteral obstruction. The cortex of the obstructed kidney produces a unique chemoattractant that is specific for macrophages. This substance behaves biochemically as a lipid, and may account (in part) for the macrophage infiltrate following ureteral obstruction.