Increased urinary albumin indicating urothelial leakage following intravesical bacillus Calmette-Guérin therapy for superficial bladder cancer

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Abstract
This study on the increase in albumin in the urine of patients with superficial bladder cancer after intravesical bacillus Calmette-Guérin (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) 1β, IL2, IL6, and tumor necrosis factor alpha (TNFα) 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 24h thereafter. The mean concentration of albumin in pre-therapy specimens was 112±118 (range 2–432) μg albumin/ml urine, approximating 14±14 μg/ μmol creatinine (creat) (n=15), which was comparable to the mean pre-instillation value of 16±32 μg/μmol creat (n=96). A significant increase in urinary albumin during the 6 weeks of BCG treatment was observed (PPr) being 0.56, 0.56, 0.67, and 0.71 (n=418), respectively. During the first 24h after instillation cytokines and albumin peaked in the following order: TNFα→IL2→albumin→IL6→IL1β. TNF peaked most frequently after 2–4h and IL1β 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 largescale investigations of the correlation between elevation of urinary albumin and (tumor) response on BCG therapy.