title: Effects of interleukin-2 immunotherapy on renal function.
abstract: Recombinant interleukin-2 (IL-2) infusions have recently been evaluated as a new form of immunotherapy for the treatment of malignancies. This form of therapy has been complicated by the development of fluid retention, azotemia, and hypophosphatemia. To evaluate the effects of IL-2 on renal function, we prospectively studied eight patients who received IL-2 (10(5) micron/kg every eight hours intravenously [IV]) for five days as the initial phase of a treatment protocol using IL-2 plus lymphokine activated killer (LAK) cells. Dopamine and fluids were used to maintain blood pressure and all patients received indomethacin (100 mg/d). IL-2 therapy produced a syndrome similar to endotoxemia with the development of respiratory alkalosis (pH = 7.44 +/- .2, pCO2 = 30 +/- 2) and hypotension (mean BP, 71.3 mm Hg). These changes were accompanied by marked sodium avidity, edema formation, and mild elevations of BUN and creatinine. Hypophosphatemia, hypocalcemia, and hypomagnesemia were commonly seen. No defects in renal calcium, magnesium, phosphorous, net acid excretion, or glycosuria were demonstrated. We conclude: (1) IL-2 induces an increase in vascular permeability causing the development of edema, sodium avidity, and prerenal azotemia as occurs during endotoxemia; (2) IL-2 therapy induces respiratory alkalosis with the subsequent intracellular shift of phosphorous accompanied by increased renal phosphorous reabsorption; and (3) there is no evidence of renal tubular dysfunction (renal tubular acidosis [RTA], renal leak of glucose, phosphorous, or magnesium).
authors.affiliation: Department of Medicine, Loyola University Medical Center, Maywood, IL 60153.
authors.forename: G A
authors.initials: GA
authors.lastname: Kozeny
authors.forename: J D
authors.initials: JD
authors.lastname: Nicolas
authors.forename: S
authors.initials: S
authors.lastname: Creekmore
authors.forename: L
authors.initials: L
authors.lastname: Sticklin
authors.forename: J E
authors.initials: JE
authors.lastname: Hano
authors.forename: R I
authors.initials: RI
authors.lastname: Fisher
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects; D000328:Adult; D000368:Aged; D002118:Calcium / Q000378:metabolism; D003110:Colonic Neoplasms / Q000628:therapy; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects*; D007674:Kidney Diseases / Q000209:etiology*; D007680:Kidney Neoplasms / Q000628:therapy; D007694:Killer Cells, Natural / Q000276:immunology; D008222:Lymphokines / Q000276:immunology; D008274:Magnesium / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000628:therapy; D008875:Middle Aged; D010758:Phosphorus / Q000378:metabolism; D012004:Rectal Neoplasms / Q000628:therapy
chemical_list: D007376:Interleukin-2; D008222:Lymphokines; D010758:Phosphorus; D008274:Magnesium; D002118:Calcium