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Cisplatin nephrotoxicity.

R Safirstein, J Winston, M Goldstein

    American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    |November 1, 1986
    PubMed
    Summary
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    Cisplatin is a vital chemotherapy drug, but its use is limited by kidney damage (nephrotoxicity). Research suggests this damage may stem from how the kidneys process and concentrate the drug, particularly in the proximal tubules.

    Area of Science:

    • Nephrology
    • Oncology
    • Pharmacology

    Background:

    • Cisplatin (cis-dichlorodiammine platinum II) is a key chemotherapy agent for solid tumors.
    • Nephrotoxicity is a major limitation, necessitating dosage adjustments and hydration.
    • The kidney's role in cisplatin excretion is linked to its susceptibility.

    Purpose of the Study:

    • To investigate the mechanisms underlying cisplatin-induced nephrotoxicity.
    • To identify specific renal cell targets and transport processes involved in cisplatin uptake.
    • To elucidate the physiological changes contributing to acute renal failure from cisplatin.

    Main Methods:

    • Analysis of cisplatin localization within renal tubules.
    • Investigation of cellular processes affecting cisplatin uptake (e.g., oxygen utilization, organic base inhibition).

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  • Measurement of renal hemodynamics and filtration rates during cisplatin exposure.

    • Main Results:

    • Cisplatin uptake by renal cells depends on oxygen and is inhibited by organic bases.
    • The S3 segment of proximal tubules shows greater platinum localization, suggesting specific uptake.
    • Reduced renal blood flow and glomerular filtration rates, with preglomerular vasoconstriction, characterize early cisplatin nephrotoxicity.

    Conclusions:

    • Cisplatin nephrotoxicity is linked to specific uptake mechanisms in proximal tubule S3 segments.
    • Renal handling of cisplatin involves active transport processes.
    • Preglomerular vasoconstriction is a significant factor in acute kidney injury induced by cisplatin.