Renal toxicity mediated by continuous infusion of recombinant interleukin-2

Interleukin-2 (IL-2), a potent lymphokine with antitumoral activity, was used in continuous intravenous infusion for 5 days (18,000,000 IU/m2/day) in 9 treatment cycles in 5 patients with metastatic colorectal carcinoma. During the infusion, patients received aggressive fluid replacement titrated by invasive hemodynamic monitoring, aiming at a stable 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 (105.4 +/- 11.6 to 86.1 +/- 12.5 mm Hg, p < 0.05), systemic vascular resistance 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 output and central venous pressure. The urinary output significantly dropped from 1.9 +/- 1.2 to 0.2 +/- 0.1 ml/min (p < 0.05) with very significant 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-glucosaminidase urinary activity from 4.97 +/- 5.0 to 23.0 +/- 12.1 U/l, 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 urinary sodium (113.8 +/- 78.3 to 9.0 +/- 6.7 mmol/l). Urine sediment evolved 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, induces an acute renal failure in most patients treated.