RENAL HEMODYNAMICS, SODIUM AND WATER REABSORPTION DURING CONTINUOUS INTRAVENOUS-INFUSION OF RECOMBINANT INTERLEUKIN-2

1. Renal haemodynamics, lithium and sodium clearance were measured in 14 patients treated with recombinant interleukin-2 for metastatic rena l cell carcinoma. 2. Patients were studied before and after 72 h of co ntinuous intravenous infusion of recombinant interleukin-2 (18 x 10(6) i.u..24 h(-1).m(-2)) and 48 h post therapy. Cardiac output was measur ed by impedance cardiography. Effective renal plasma flow and glomerul ar filtration rate were determined by the renal clearances of I-131-hi ppuran and Tc-99m-diethylenetriaminepenta-acetic acid (DTPA) respectiv ely. Renal clearance of lithium (C-Li) was used as an index of proxima l tubular outflow. 3. Treatment caused a transient decrease in mean ar terial blood pressure and systemic vascular resistance, but cardiac ou tput remained unchanged. Renal blood flow decreased and renal vascular resistance increased during and after treatment. Sodium clearance dec reased from 1.10 (0.63/1.19) ml/min to 0.17 (0.18/0.32) ml/min (P = 0. 003). Glomerular filtration rate remained unchanged, whereas the media n C-Li decreased from 26 (17/32) ml/min to 17 (10/21) ml/min (P = 0.00 8). Calculated absolute proximal reabsorption rate of water increased from 63 (40/69) ml/min to 71 (47/82) ml/min (P = 0.04). The urinary ex cretion rate of thromboxane B-2, and the ratio between excretion rates of thromboxane B-2, and 6-keto-prostagtandin-F-1 alpha, increased by 98% (P = 0.022) and 175% (P = 0.022) respectively. 4. The study sugges ts a specific recombinant interleukin-2-induced renal vasoconstrictor effect. Changes in renal prostaglandin synthesis may contribute to the decrease in renal blood flow. The lithium clearance data suggest that an increased proximal tubular reabsorption rate may contribute to the decreased sodium clearance during recombinant interleukin-2 treatment .