RENAL IMPAIRMENT ASSOCIATED WITH THE PREOPERATIVE ADMINISTRATION OF RECOMBINANT INTERLEUKIN-2

1. The T-cell-derived cytokine interleukin-2 may be used to reverse th e immune suppression associated with major surgery. However, both majo r surgical procedures and recombinant interleukin-2 therapy are known to induce renal dysfunction. 2. Eighteen patients were randomized to r eceive either recombinant interleukin-2 (18 x 10(6) i.u./day) or place bo, given subcutaneously for 3 days before undergoing curative colorec tal cancer surgery. Indices of renal function were determined pre-oper atively and for 21 days after surgery. 3. Pre-operative recombinant in terleukin-2 was found to significantly increase, compared with placebo controls, N-acetyl-beta-D-glucosaminidase [peak levels 28 (SEM 2) ver sus 11 (SEM 3) i.u./mmol of Cr] and gamma-glutamyltransferase [peak le vels 5.3 (SEM 0.6) versus 2.4 (SEM 0.2) i.u./mmol/l] and decrease urin ary fractional excretion of sodium [peak difference 0.32 (SEM 0.06) ve rsus 0.76 (SEM 0.08)] (all P < 0.05). Significantly increased urinary excretions of creatinine, N-acetyl-beta-D-glucosaminidase and gamma-gl utamyltransferase were also identified after surgery. All variables re turned to pretreatment limits by the seventh day post-operatively, exc ept N-acetyl-beta-D-glucosaminidase, which was still significantly ele vated 21 days after surgery. No differences in the serum concentration s of sodium, creatinine or urea were observed before or after surgery in either group. 4. Recombinant interleukin-2, when given in the preop erative period, was associated with significant renal dysfunction. How ever, routine monitoring of serum indices (i.e. sodium, urea, creatini ne and albumin) failed to detect such renal damage. These results sugg est that, with the use of recombinant interleukin-2 to enhance natural cytotoxicity in the peri-operative period, such therapy may potentiat e the renal impairment occurring after surgery.