Renal effects of continuous infusion of recombinant interleukin-2 in children.
Recombinant interleukin-2 (rIL-2) is a new promising treatment for cancer, but is associated with severe renal toxicity. This study is the first to analyse the renal effects of rIL-2 in children. Twenty-one cycles of continuous rIL-2 infusion were studied in 15 patients; mean age was 6.9 years and average weight 18.9 kg. Interstitial fluid retention and oliguria (baseline, 1.7 ml/kg per hour; nadir, 0.5 mg/kg per hour) were associated with hypotension (baseline, 101/56 mm Hg; nadir, 85/43 mm Hg) and decreased intravascular volume (plasma renin activity increased x 10). Weight gain (+7.9%) was observed in 13 cycles whereas weight loss (-6.3%) was shown in 8 cycles because of digestive and cutaneous losses, mainly in the youngest patients. This prerenal azotaemia was characterized by a decrease in creatinine clearance (from 101 to 36 ml/min per 1.73 m2) and a low fractional excretion of sodium (FENa) (from 0.70% to 0.09%). Hypotension and hypovolaemia needed vascular filling (n = 12), dopamine (n = 7) and interruption of rIL-2 (n = 2). Most abnormalities occurred as early as day 2 of therapy and were always reversible after a short period with sodium leakage (diuresis = 2.2 ml/kg per hour, FENa = 2.01%). Hypophosphataemia was associated with low urinary excretion of phosphorus, suggesting an increased uptake of inorganic phosphorus by rapidly proliferating lymphoid cells.
Cochat
P
P
Paediatric Renal Unit, E. Herriot Hospital, Lyon, France.
Floret
D
D
Bouffet
E
E
Francks
C R
CR
Favrot
M C
MC
Philip
T
T
David
L
L
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009369:Neoplasms / Q000628:therapy; D010758:Phosphorus / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D014511:Uremia / Q000139:chemically induced
D007376:Interleukin-2; D011994:Recombinant Proteins; D010758:Phosphorus