RENAL TOXICITY MEDIATED BY CONTINUOUS INFUSION OF RECOMBINANT INTERLEUKIN-2

Interleukin-2 (IL-2), a potent lymphokine with antitumoral activity, w as used in continuous intravenous infusion for 5 days (18,000,000 IU/m 2/day) in 9 treatment cycles in 5 patients with metastatic colorectal carcinoma. During the infusion, patients received agressive fluid repl acement titrated by invasive hemodynamic monitoring, aiming at a stabl e central volemia. Body weight went up an average of 4.5 kg in 5 days, mean arterial blood pressure dropped slightly from day 1 to day 5 (10 5.4 +/- 11.6 to 86.1 +/- 12.5 mm Hg, p < 0.05), systemic vascular resi stance decreased from 1304.7 +/- 242.1 to 871.7 +/- 237.2 dyn/s/cm-5 ( p < 0.05), with stable pulmonary capillary wedge pressure, cardiac out put and central venous pressure. The urinary output significantly drop ped from 1.9 +/- 1.2 to 0.2 +/- 0.1 ml/min (p < 0.05) with very signif icant rises in serum creatinine from 76.0 +/- 28.3 to 242.2 +/- 144.9 mumol/l (0.86 +/- 0.32 to 2.47 +/- 1.64 mg/dl) and N-acetyl-beta-D-glu cosaminidase urinary activity from 4.97 +/- 5.0 to 23.0 +/- 12.1 U/1, and significant decrement of creatinine clearance (1.86 +/- 0.65 to 0. 29 +/- 0.27 ml/s or 111.5 +/- 38.9 to 17.1 +/- 16.6 ml/min) and urinar y sodium (I 13.8 +/- 78.3 to 9.0 +/- 6.7 mmol/l). Urine sediment evolv ed from normal at day 1 to 9.0 +/- 3.7 epithelial cells/mm3 and 6.9 +/ - 3.6 brown casts/mm3 (p = 0.001). We concluded that cancer treatment with IL-2 in continuous infusion, even with stable hemodynamics, induc es an acute renal failure in most patients treated.