The role of possible risk factors for acute and late renal dysfunction after high-dose interleukin-2, interferon alpha and lymphokine-activated killer cells

Renal dysfunction is a frequently encountered adverse event following treat ment with high-dose interleukin-2 (IL-2). Information about parameters pred icting the severity of IL-2-associated renal function abnormalities is limi ted. In this study the role of possible risk factors in the development of high-dose IL-2-associated acute and long-term renal dysfunction was investi gated. A total of 72 patients, who were treated with a regimen consisting o f IL-2 (18 MIU m(-2) day(-1) by continuous infusion), interferon alpha (IFN alpha; 5 MIU m(-2) day(-1), intramuscularly) and lymphokine-activated kill er (LAK) lymphocytes, were analysed. Serum creatinine measurements were per formed daily during treatment, weekly between courses and monthly during fo llow-up. Pre-and posttreatment 24-h urine samples were collected for calcul ation of creatinine clearances. Renal dysfunction was observed in 97% of pa tients. Grade 1 dysfunction (according to WHO criteria) was observed in 20 patients (28%), grade 2 in 37 (51%), grade 3 in 13 (14%) and grade 4 in 0 ( 0%). Renal dysfunction was reversible in more than 90% of patients. Only 6 patients (8%) suffered a certain amount of permanent function loss. More se vere acute renal dysfunction occurred in patients who were experiencing hyp ertension prior to treatment, those who suffered sepsis during treatment an d in men than in women. Sepsis was also associated with irreversible functi on loss. Other variables such as age, performance status, diabetes mellitus , interval between nephrectomy and start of IL-2 therapy and hypotension du ring treatment were not important. In conclusion, with high-dose IL-2, rena l dysfunction develops in almost every patient and such abnormalities are m ostly reversible. Predictors for severe acute renal dysfunction are pre-exi sting hypertension, sepsis and sex. A septic episode also carries a risk of permanent damage.