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/m2/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 micrograms/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.(ABSTRACT TRUNCATED AT 250 WORDS)
Memoli
B
B
Department of Nephrology, University Federico II of Naples, Italy.
De Nicola
L
L
Libetta
C
C
Scialò
A
A
Pacchiano
G
G
Romano
P
P
Palmieri
G
G
Morabito
A
A
Lauria
R
R
Conte
G
G
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D000368:Aged; D000704:Analysis of Variance; D001798:Blood Proteins / Q000378:metabolism; D003404:Creatinine / Q000378:metabolism; D004298:Dopamine / Q000008:administration & dosage*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000009:adverse effects*; D007680:Kidney Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000009:adverse effects; D012964:Sodium / Q000652:urine
D001798:Blood Proteins; D007376:Interleukin-2; D011994:Recombinant Proteins; D012964:Sodium; D003404:Creatinine; D004298:Dopamine