Cisplatin Nephrotoxicity

R. Safirstein, J. Winston, M. Goldstein, D. Moel, S. Dikman, J. Guttenplan

Research output: Contribution to journalArticlepeer-review

Abstract

Cis-dichlorodiammine platinum (II), or Cisplatin, has emerged as a principal chemotherapeutic agent in the treatment of otherwise resistant solid tumors and is currently among the most widely used agents in the chemotherapy of cancer. The chief limit to its greater efficacy is its nephrotoxicity, which has made it necessary both to lower its dosage and actively hydrate patients to reduce it. The vulnerability of the kidney to cisplatin is almost certainly related to its primary role in the excretion of cisplatin. Cisplatin enters renal cells by a process that depends on normal oxygen utilization and is specifically inhibited by organic bases. Greater localization of platinum to the S3 segment of the proximal tubules suggests that the vulnerability of this segment may depend on its specific uptake of the drug. The majority of intracellular platinum is bound to macromolecules, including protein and DNA, yet a significant portion of cell platinum is biotransformed to a nonmutagenic and possibly nontoxic compound. Polyuria and hypomagnesemia, which are commonly associated with cisplatin nephrotoxicity, may be due to defects in deep nephron or collecting duct fluid and solute transport. Low single nephron glomerular filtration rates (SNGFR) during early cisplatinum-induced acute renal failure is accompanied by reduced renal blood flow and transglomerular hydrostatic pressure without elevated intratubular hydrostatic pressure, suggesting preglomerular vasoconstriction as an important determinant of renal failure. The critical intracellular pathogenetic effects of cisplatin that are responsible for its renal cytotoxicity are unknown, but since abnormalities in renal function are preceded by a period where gross renal function appears normal, it is an ideal model to study the early physiologic and biochemical determinants of acute renal failure.

Original languageEnglish (US)
Pages (from-to)356-367
Number of pages12
JournalAmerican Journal of Kidney Diseases
Volume8
Issue number5
DOIs
StatePublished - 1986

Keywords

  • Polyuric renal failure
  • glomerular filtration rate (GFR)
  • organic base transport
  • tubule respiration

ASJC Scopus subject areas

  • Nephrology

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