Interleukin-2-induced Renal Dysfunction In Cancer-patients Is Reversed By Low-dose Dopamine Infusion

Recombinant interleukin-2 (rIL-2) is widely used in patients with advanced cancer to enhance killer cell functions. However, the main drawback of rIL-2 therapy is the frequent development of oliguric acute renal failure (ARF), presumably due to a vascular leak syndrome. The aim of this study was to evaluate the effect of low-dose dopamine infusion on this form of ARF, Nine patients with metastatic renal cancer and previous unilateral nephrectomy were treated with a continuous intravenous infusion of rIL-2 (3 x 10(6) Cetus units/m(2)/d) for 5 days (study A). After 1 week, all the patients repeated the same cycle, but with the addition of a continuous intravenous infusion of dopamine (2 mu g/min/kg body weight) that was started at the third day of treatment (study B), During study A, all patients showed a progressive (up to 34%) decrease of creatinine clearance. After rIL-2 withdrawal, these alterations persisted and were associated with a reduction in urinary output, sodium urinary excretion, and plasma protein, In study B, dopamine administration after renal function impairment (Delta glomerular filtration rate = -44%) led to a prompt improvement of creatinine clearance, Creatinine clearance showed a further significant enhancement after the withdrawal of both drugs, reaching a value within the baseline range on the third day of follow-up, Similarly, the decline in urinary output and sodium excretion during rIL-2 was promptly counteracted by dopamine; in addition, after withdrawal of rIL-2 and dopamine, plasma protein levels were normalized, In conclusion, our data suggest that rIL-2-induced ARF in cancer patients is due to renal hypoperfusion mainly caused by a reduction in oncotic pressure, Importantly, intravenous infusion of dopamine at low dosage is effective in reversing this form of renal impairment; such a therapeutic approach, while reducing recovery time, avoids dose reduction or discontinuation of rIL-2 treatment. (C) 1995 by the National Kidney Foundation, Inc.