Renal impairment associated with the pre-operative administration of recombinant interleukin-2.
1. The T-cell-derived cytokine interleukin-2 may be used to reverse the immune suppression associated with major surgery. However, both major surgical procedures and recombinant interleukin-2 therapy are known to induce renal dysfunction. 2. Eighteen patients were randomized to receive either recombinant interleukin-2 (18 x 10(6) i.u./day) or placebo, given subcutaneously for 3 days before undergoing curative colorectal cancer surgery. Indices of renal function were determined pre-operatively and for 21 days after surgery. 3. Pre-operative recombinant interleukin-2 was found to significantly increase, compared with placebo controls, N-acetyl-beta-D-glucosaminidase [peak levels 28 (SEM 2) versus 11 (SEM 3) i.u./mmol of Cr] and gamma-glutamyltransferase [peak levels 5.3 (SEM 0.6) versus 2.4 (SEM 0.2) i.u./mmol/l] and decrease urinary fractional excretion of sodium [peak difference 0.32 (SEM 0.06) versus 0.76 (SEM 0.08)] (all P < 0.05). Significantly increased urinary excretions of creatinine, N-acetyl-beta-D-glucosaminidase and gamma-glutamyltransferase were also identified after surgery. All variables returned to pretreatment limits by the seventh day post-operatively, except N-acetyl-beta-D-glucosaminidase, which was still significantly elevated 21 days after surgery. No differences in the serum concentrations of sodium, creatinine or urea were observed before or after surgery in either group. 4. Recombinant interleukin-2, when given in the preoperative period, was associated with significant renal dysfunction. However, routine monitoring of serum indices (i.e. sodium, urea, creatinine and albumin) failed to detect such renal damage.(ABSTRACT TRUNCATED AT 250 WORDS)
Deehan
D J
DJ
Department of Surgery, University of Aberdeen, Scotland, UK.
Heys
S D
SD
Broom
J
J
Eremin
O
O
Whiting
P H
PH
D000118:Acetylglucosaminidase / Q000652:urine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000601:surgery; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009318:Natriuresis; D011184:Postoperative Period; D011292:Premedication; D011994:Recombinant Proteins / Q000009:adverse effects; D012709:Serum Albumin / Q000378:metabolism; D012964:Sodium / Q000097:blood; D014508:Urea / Q000097:blood; D014556:Urine; D005723:gamma-Glutamyltransferase / Q000652:urine
D007376:Interleukin-2; D011994:Recombinant Proteins; D012709:Serum Albumin; D014508:Urea; D012964:Sodium; D003404:Creatinine; D005723:gamma-Glutamyltransferase; D000118:Acetylglucosaminidase