Cisplatin causes dose-limiting nephrotoxicity. To prevent it, forced saline diuresis with intravenous hydration is mandatory. Which pharmacological property of cisplatin explains why it accumulates in renal proximal tubular cells?

• A Cisplatin is highly plasma protein bound (>99%), escaping glomerular filtration and accumulating in tubular cells via secretion
• B Cisplatin inhibits megalin, blocking renal cortical endocytosis of filtered proteins and causing secondary tubular toxicity
• C Cisplatin activates P-glycoprotein in the proximal tubule, causing active secretion and re-entry cycling
• D Cisplatin is transported into proximal tubular cells by organic cation transporters (OCT2) and copper transporter 1 (CTR1), concentrating the drug intracellularly ✓

Explanation

Cisplatin enters renal proximal tubular cells via active transport through organic cation transporter 2 (OCT2, SLC22A2) and copper transporter 1 (CTR1). These transporters concentrate cisplatin inside tubular cells to levels far exceeding plasma concentrations, where it forms platinum-DNA adducts and platinum-protein adducts that cause oxidative stress, mitochondrial dysfunction and apoptosis. Genetic polymorphisms in OCT2 modify nephrotoxicity risk. Saline hydration reduces tubular cisplatin concentration by dilution and increased flow. Amifostine (a thiol donor) is used as a nephroprotective agent.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.