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Cancer chemotherapy-induced tubular nephrotoxicity evaluated by immunochemical determination of urinary adenosine
Abstract:
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.
Insights
Urinary adenosine deaminase binding protein (ADB) levels can detect drug-induced kidney damage in children undergoing chemotherapy. Increased ADB excretion indicates tubular nephrotoxicity before serum creatinine changes occur.
Area of Science:
- Nephrology
- Pharmacology
- Oncology
Background:
- Drug-induced nephrotoxicity is a significant concern in pediatric cancer patients receiving chemotherapy.
- Early detection of kidney damage is crucial for managing treatment and preventing long-term complications.
Purpose of the Study:
- To evaluate the utility of adenosine deaminase binding protein (ADB) as a biomarker for detecting drug-induced tubular nephrotoxicity in children.
- To assess if ADB measurements can identify subclinical kidney injury before overt clinical signs appear.
Main Methods:
- Serial urine samples were collected from 12 children undergoing chemotherapy for solid tumors.
- Urinary ADB concentrations were measured immunochemically.
- ADB levels were compared with the administration of nephrotoxic and non-nephrotoxic chemotherapy agents.
- ADB assay results were correlated with enzymatic assays and proteinuria.
Main Results:
- Urinary ADB concentrations increased significantly (greater than fivefold) in patients receiving nephrotoxic drugs (cisplatin, methotrexate, ifosfamide) but not with non-nephrotoxic drugs (etoposide, doxorubicin).
- Elevated ADB levels preceded increases in serum creatinine in patients treated with cisplatin or ifosfamide.
- ADB assay results showed good correlation with N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase enzymatic assays.
Conclusions:
- Serial urinary ADB measurements are a sensitive indicator of acute subclinical nephrotoxicity in children receiving chemotherapy.
- ADB may serve as a valuable tool for screening investigational drugs for potential kidney toxicity during early clinical trials.