open access (2014) Pathophysiology of Cisplatin-Induced Acute Kidney Injury

open access

Abstract

Cisplatin and other platinum derivatives are the most widely used chemotherapeutic agents to treat solid tumors including ovarian, head and neck, and testicular germ cell tumors. A known complication of cisplatin administration is acute kidney injury (AKI). The nephrotoxic effect of cisplatin is cumulative and dose-dependent and often necessitates dose reduction or withdrawal. Recurrent episodes of AKI may result in chronic kidney disease. The pathophysiology of cisplatin-induced AKI involves proximal tubular injury, oxidative stress, inflammation, and vascular injury in the kidney. There is predominantly acute tubular necrosis and also apoptosis in the proximal tubules. There is activation of multiple proinflammatory cytokines and infiltration of inflammatory cells in the kidney. Inhibition of the proinflammatory cytokines TNF-α or IL-33 or depletion of CD4+ T cells or mast cells protects against cisplatin-induced AKI. Cisplatin also causes endothelial cell injury. An understanding of the pathogenesis of cisplatin-induced AKI is important for the development of adjunctive therapies to prevent AKI, to lessen the need for dose decrease or drug withdrawal, and to lessen patient morbidity and mortality.

1. Introduction

Acute kidney injury (AKI) is defined as a clinical syndrome characterized by a rapid decrease in renal (kidney) function together with the accumulation of waste products such as urea [1]. The incidence of non-dialysis-requiring AKI is about 5000 cases per million people per year and incidence of dialysis requiring AKI is 295 cases per million people per year [2]. AKI complicates 1–7% of all hospital admissions and 1–25% of intensive care unit admissions [3, 4]. Furthermore, AKI is known as an independent risk factor for mortality. AKI increases the risk of death by 10- to 15-fold and results in a mortality rate of 50% [5, 6]......