INCREASED URINARY ALBUMIN INDICATING UROTHELIAL LEAKAGE FOLLOWING INTRAVESICAL BACILLUS-CALMETTE-GUERIN THERAPY FOR SUPERFICIAL BLADDER-CANCER

This study on the increase in albumin in the urine of patients with superficial bladder cancer after intravesical bacillus Calmette-Guerin (BCG) treatment was initiated on the basis of two facts. First, extravasation of serum albumin could be expected as a result of the BCG-induced delayed-type hypersensitivity reaction in the bladder wall. Second, appearance of albumin in the urine was a possibility as cytokines also appear in the urine, although probably after being produced suburothelially by infiltrating leukocytes. Albumin and the cytokines interleukin (IL)1beta, IL2, IL6, and tumor necrosis factor alpha (TNFalpha) were determined in urine from 20 patients treated with 6 weekly intravesical BCG instillations, collected prior to each instillation and 2, 4, 6, 8, 12, and 24 h thereafter. The mean concentration of albumin in pre-therapy specimens was 112 +/- 118 (range 2-432) mug albumin/ml urine, approximating 14 +/-14 mug/mumol creatinine (creat) (n = 15), which was comparable to the mean pre-instillation value of 16 +/- 32 mug/mumol creat (n = 96). A significant increase in urinary albumin during the 6 weeks of BCG treatment was observed (P < 0.001). However, a large variation existed between individual patients and in some patients no reaction was seen. Maximum albumin concentrations were observed after instillations 3-6. A significant correlation between albumin and concentration of the cytokines IL1beta, IL2, IL6, and TNFalpha was found (P < 0.01), correlation coefficients (r) being 0.56, 0.56, 0.67, and 0.71 (n = 418), respectively. During the first 24 h after instillation cytokines and albumin peaked in the following order: TNFalpha --> IL2 --> albumin --> IL6 --> IL1beta. TNF peaked most frequently after 2-4h and IL1beta after 6h, while IL2, albumin, and IL6 peaked between these time points. In conclusion, the presence of albumin in urine indicates a ''leakiness'' of the bladder wall after repeated BCG instillations. Since albumin was shown to be stable in urine and the assay is relatively simple and cheap, it may be performed in most hospitals. This will allow large-scale investigations of the correlation between elevation of urinary albumin and (tumor) response on BCG therapy.