Acute renal dysfunction during interleukin-2 treatment: suggestion of an intrinsic renal lesion.
Adoptive immunotherapy with interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells has been effective in treating some advanced malignancies in animals and humans. One complication of this treatment is a reversible, oliguric, acute renal failure, which has been ascribed to renal hypoperfusion and resultant prerenal azotemia. We serially studied renal function in 10 patients receiving high-dose regimens of recombinant interleukin-2 (rIL-2) to attempt to delineate further the nature of the renal dysfunction caused by IL-2 treatment. Renal plasma flow was computed from iodine 131 (I-131 Hippuran; Mediphysics, Paramus, NJ) orthoiodohippurate, excretion curves, and glomerular filtration rate (GFR) was determined by creatinine clearance. Studies done prior to and on day 4 of treatment showed that GFR fell in nine of 10 patients, with a mean decrease of 43% +/- 8%, and renal plasma flow fell in five of the 10 patients with a mean decrease of 5% +/- 10%. The average pretherapy filtration fraction was calculated to be 23% +/- 1% and after 4 days of treatment, decreased to a mean value of 15 +/- 2%. The BUN to creatinine ratio also declined in all patients. These findings collectively suggest that IL-2 nephrotoxicity may result from an intrarenal defect in addition to the previously described prerenal azotemia. Additionally, radionuclide studies of renal function are a reliable and reproducible noninvasive method of assessing these changes in renal function.
Shalmi
C L
CL
Department of Oncology, Albert Einstein Cancer Center/Montefiore Medical Center, Bronx, NY 10467-2490.
Dutcher
J P
JP
Feinfeld
D A
DA
Chun
K J
KJ
Saleemi
K R
KR
Freeman
L M
LM
Lynn
R I
RI
Wiernik
P H
PH
D058186:Acute Kidney Injury / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology; D000328:Adult; D001806:Blood Urea Nitrogen; D003131:Combined Modality Therapy; D003404:Creatinine / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007376:Interleukin-2 / Q000009:adverse effects* / Q000627:therapeutic use; D007668:Kidney / Q000503:physiopathology*; D015979:Killer Cells, Lymphokine-Activated; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000503:physiopathology / Q000628:therapy*; D011446:Prospective Studies; D011877:Radionuclide Imaging; D012079:Renal Circulation
D007376:Interleukin-2; D003404:Creatinine