Background and objective: Contrast-induced acute kidney injury (CI-AKI) is a serious complication
of the administration of iodinated contrast media (CM) for diagnostic and interventional cardiovascular
procedures and is associated with substantial morbidity and mortality. While the preventative
measures can mitigate the risk of CI-AKI, there remains a need for novel and effective therapeutic approaches.
The pathogenesis of CI-AKI is complex and not completely understood. CM-induced renal
tubular cell apoptosis caused by the activation of endoplasmic reticulum (ER) stress is involved in CIAKI.
We previously demonstrated that valsartan alleviated CM-induced human renal tubular cell apoptosis
by inhibiting ER stress in vitro. However, the nephroprotective effect of valsartan on CI-AKI in vivo
has not been investigated. Therefore, the aim of this study was to explore the protective effect of valsartan
in a rat model of CI-AKI by measuring the amelioration of renal damage and the changes in ER stressrelated
Method and Results: Our results showed that the radiocontrast agent meglumine diatrizoate caused significant
renal insufficiency, renin-angiotensin system (RAS) activation, and renal tubular apoptosis by
triggering ER stress through activation of glucose-regulated protein 78 (GRP78), activating transcription
factor 4 (ATF4), caspase 12, CCAAT/enhancer-binding protein-homologous protein (CHOP) and c-Jun
N-terminal protein kinase (JNK) (P<0.05; n=6 in each group). Pre-treatment with valsartan significantly
alleviated renal dysfunction, pathological injury, and apoptosis along with the inhibition of ER stressrelated
biomarkers (P<0.05; n=8 in each group).
Conclusion: Valsartan could protect against meglumine diatrizoate-induced kidney injury in rats by inhibiting
the ER stress-induced apoptosis, making it a promising strategy for preventing CI-AKI.