Cancer chemotherapy-induced tubular nephrotoxicity evaluated by immunochemical determination of urinary adenosine deaminase binding protein.
The authors evaluated measurements of adenosine deaminase binding protein (ADB), a proximal renal tubular cell antigen, for detection of drug-induced tubular nephrotoxicity. Concentrations of ADB were determined immunochemically in serial urine specimens from 12 children who were receiving chemotherapy for malignant solid tumors. There was no indication of increased ADB excretion after administration of two nonnephrotoxic drugs, etoposide and doxorubicin, but in patients given the recognized nephrotoxins, cisplatin and methotrexate, or an investigational drug, ifosfamide, urinary concentrations of ADB increased greater than fivefold relative to baseline values. Increased ADB concentrations preceded cisplatin- or ifosfamide-induced elevations of serum creatinine. Results of the ADB assay correlated well with those obtained by enzymatic assays for N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase (r = 0.76 and 0.53; n = 142, P less than 0.001) and marginally with total proteinuria (r = 0.21; P less than 0.02). Hence, serial ADB measurements may be useful in screening investigational drugs for acute subclinical nephrotoxicity.
D000970:Antineoplastic Agents / Q000506:poisoning*; D002352:Carrier Proteins / Q000652:urine*; D002648:Child; D002675:Child, Preschool; D018819:Dipeptidyl Peptidase 4; D006801:Humans; D007069:Ifosfamide / Q000506:poisoning; D007120:Immunochemistry; D007674:Kidney Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000652:urine; D007684:Kidney Tubules / Q000187:drug effects*; D009994:Osmolar Concentration
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D018819:Dipeptidyl Peptidase 4; D007069:Ifosfamide