Urinastatin (Kunitz-type proteinase inhibitor) reducing cisplatin nephrotoxicity

The authors investigated the reductive effects of a Kunitz-type proteinase inhibitor, urinastatin, on the nephrotoxicity seen in lung cancer patients treated with cisplatin by measuring N-acetyl-beta-D-glucosaminidase (NAG) activity and beta 2-microglobulin (BMG) content in 24 hour urine, creatinine clearance, blood urea nitrogen (BUN), serum creatinine, uric acid, and BMG as factors of nephrotoxicity. In control patients treated with anticancer drugs containing cisplatin but no supplemental urinastatin, the 24 hour urine NAG and BMG levels increased more than three-fold over the pretreatment levels, 3 days after anticancer therapy, respectively. Creatinine clearance significantly decreased and levels of BUN, serum uric acid, and BMG in control patients significantly increased over the corresponding pretreatment levels, 3 days after anticancer therapy. However, supplemental urinastatin reduced abnormalities in levels of all these factors 3 days after therapy. These results suggest that supplemental urinastatin protects from cisplatin-induced nephrotoxicity, especially proximal tubular damage.