URINARY EPIDERMAL GROWTH-FACTOR IS EXCRETED FROM THE RAT ISOLATED-PERFUSED KIDNEY IN THE ABSENCE OF PLASMA

Large amounts of epidermal growth factor (EGF) are excreted in urine a nd the majority of this urinary EGF appears to be of renal origin. EGF is synthesized in the kidneys as a membrane-bound 160 kDa precursor, in the thick ascending limb of Henle and in the early part of the dist al convoluted tubule. Very little is known about how EGF is released f rom cell membranes into urine but proteolytic cleavage of the membrane -bound EGF precursor seems likely. The purpose of this study was to ex amine whether plasma constituents are necessary for urinary excretion of EGF. In the rat isolated kidney perfused at a pressure of 90 mmHg w ith a modified Krebs-Henseleit buffer containing oncotic agents, the q uantity of EGF excreted into the ureteral effluent was 67% of the amou nt excreted by the rat kidney in vivo. The EGF excreted by the isolate d kidney behaved like urinary EGF upon gel filtration. Administration of the proteinase inhibitor aprotinin reduced urinary EGF excretion fr om the rat isolated perfused kidney by approximately 50%. In conclusio n, the rat isolated perfused kidney excreted significant amounts of ur inary EGF without having access to plasma, and EGF excretion was reduc ed by aprotinin. This is further evidence suggesting an intrarenal sou rce of urinary EGF and suggests that the EGF precursor in the rat kidn ey is processed by enzyme(s) of renal origin.