title: Renal haemodynamics, sodium and water reabsorption during continuous intravenous infusion of recombinant interleukin-2.
abstract: 1. Renal haemodynamics, lithium and sodium clearance were measured in 14 patients treated with recombinant interleukin-2 for metastatic renal cell carcinoma. 2. Patients were studied before and after 72 h of continuous intravenous infusion of recombinant interleukin-2 (18x10(6) i.u..24 h-1.m-2) and 48 h post therapy. Cardiac output was measured by impedance cardiography. Effective renal plasma flow and glomerular filtration rate were determined by the renal clearances of 131I-hippuran and 99mTc-diethylenetriaminepenta-acetic acid (DTPA) respectively. Renal clearance of lithium (CLi) was used as an index of proximal tubular outflow. 3. Treatment caused a transient decrease in mean arterial blood pressure and systemic vascular resistance, but cardiac output remained unchanged. Renal blood flow decreased and renal vascular resistance increased during and after treatment. Sodium clearance decreased 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 median CLi decreased from 26 (17/32) ml/min to 17 (10/21) ml/min (P=0.008). 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 excretion rate of thromboxane B2 and the ratio between excretion rates of thromboxane B2 and 6-keto-prostaglandin-F1alpha increased by 98% (P=0.022) and 175% (P=0.022) respectively. 4. The study suggests 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.
authors.affiliation: Departments of Oncology, Clinical Chemistry, and Clinical Physiology, Herlev Hospital, University of Copenhagen, DK-2730 Herlevi, Denmark.
authors.forename: P F
authors.initials: PF
authors.lastname: Geertsen
authors.forename: H
authors.initials: H
authors.lastname: von der Maase
authors.forename: N V
authors.initials: NV
authors.lastname: Olsen
authors.forename: N
authors.initials: N
authors.lastname: Fogh-Andersen
authors.forename: S L
authors.initials: SL
authors.lastname: Nielsen
authors.forename: P P
authors.initials: PP
authors.lastname: Leyssac
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage*; D007457:Iodine Radioisotopes; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology*; D007680:Kidney Neoplasms / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D008094:Lithium / Q000652:urine; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012964:Sodium / Q000378:metabolism*; D018709:Statistics, Nonparametric; D016284:Technetium Tc 99m Pentetate; D013929:Thromboxane B2 / Q000652:urine; D014655:Vascular Resistance / Q000187:drug effects; D014867:Water / Q000378:metabolism*
chemical_list: D007376:Interleukin-2; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D014867:Water; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D008094:Lithium; D012964:Sodium; D016284:Technetium Tc 99m Pentetate