Cisplatin-Associated Nephrotoxic Effects in Children

Abstract

Cisplatin has been an important component of chemotherapy for cure and control of several pediatric and adult malignant tumors. Nephrotoxic effects of cisplatin are a limitation of cisplatinbased chemotherapy and are often prohibitive of further treatment with cisplatin, when they occur.However, this adverse effect is not uniformly manifested among all patients who receive cisplatinbased chemotherapy. 1 During the past few decades, investigators have attempted to identify risk factors that predispose certain patients to nephrotoxic effects of cisplatin while sparing others.Interindividual variability in kidney injury associated with cisplatin is greater than that explained by pharmacokinetic differences among patients. 2 What, if anything, can practitioners at the point of care do to ameliorate this risk of cisplatin-associated acute kidney injury (AKI) and subsequent chronic kidney disease while preserving the anticancer benefit? Common themes have emerged from the collective body of published work. Risk factors, such as age, cisplatin dose, concomitant chemotherapy, and administration of nephrotoxins, have been identified. However, these findings largely stem from retrospective studies 3 with varying study designs, patient selection algorithms, sample sizes, length of follow-up, and overall rigor. In addition, few studies thus far have homed in on risk factors in the pediatric population. McMahon et al 4 report on a prospectively evaluated, multicenter, pediatric cohort of early and late risk factors for nephrotoxic effects of cisplatin. The prospective study design, multicenter recruitment, rigorous methods, and robust statistical analysis are strengths of their study.

Cisplatin triggers oxidative stress, apoptosis and pro‐inflammatory responses by inhibiting the SIRT1‐mediated Nrf2 pathway in chondrocytes

“…Of concern, long‐term adverse health effects among children receiving cancer treatments have been described in various studies. For instance, it has been shown that radiation to the pancreas increases the risk of diabetes mellitus 4 or chemotherapy results in gonadotoxicity, 5 ototoxicity, 6 or nephrotoxicity 7 in children. Besides, several investigations have shown that chemotherapeutic agents affect the proliferative capacity of growth plate chondrocytes, leading to a decrease in growth rate 8–11 .…”

Protective effect of kaempferol against cisplatin-induced acute ovarian damage in a mouse model

“…Accepted: April 27, 2022 2012). However, its use is associated with serious side effects, including ovarian toxicity (Motwani and Curhan, 2020;Rybak et al, 2019). This toxicity is due to an imbalance between antioxidant capacity and reactive oxygen species (ROS) production, which leads to mitochondrial and DNA damage and consequent follicle death (Barberino et al, 2017;Lins et al, 2020).…”