CLINICAL-VALUE OF FRUCTOSE 1,6-BISPHOSPHATASE IN MONITORING RENAL PROXIMAL TUBULAR INJURY

The usefulness of the gluconeogenic key enzyme fructose 1,6 bisphospha tase (FBPase), which is localized exclusively in the proximal nephron segment, as a marker compound to monitor injury of the proximal nephro n segment during nephrotoxic therapy, was tested in a collective model of male patients treated for testicular cancer. These patients with n ormal kidney function were submitted to therapy with the nephrotoxic c hemotherapeutics carboplatinum and a combination of cisplatinum, etopo side, bleomycin and ifosfamide. The release of FBPase activities into the urine was monitored during the initial two treatments over a perio d of eight days. The urinary enzyme activities measured were compared to the excretion of the ''proximal tubular injury markers'' N-acetyl-b eta-D-glucosaminidase (NAG) and alpha(1)-microglobulin (alpha(1)m). Th e presence of glomerular damage was determined by measurement of urina ry excretion rates of albumin (ALB) and IgG. In addition, protein excr etion patterns following chemotherapy were monitored. The combined adm inistration of cisplatin, etoposide and ifosfamide resulted in a prono unced proximal tubular injury as shown by the release of FBPase into t he urine. This is substantiated by simultaneously increased excretion rates for NAG and alpha(1)m. Proximal tubular toxicity was found to be less severe when cisplatin was combined with etoposide and bleomycin and was nearly absent following carboplatinum monotherapy. Carboplatin um only affected glomerular function and resulted in an elevated ALB a nd IgG excretion. From this model investigation it can be delineated t hat determination of urinary FBPase activities ensures a sensitive and reliable identification of proximal nephron damage.