Air Pollution Aggravates Renal Ischemia-Reperfusion-Induced Acute Kidney Injury

Abstract

Chronic kidney disease (CKD) has emerged as a significant global public health concern. Recent epidemiological studies have highlighted the link between exposure to fine particulate matter (PM2.5) and declined renal function. PM2.5 exerts its harmful effects on various organs through oxidative stress and inflammation. Acute kidney injury (AKI) resulting from ischemia reperfusion injury (IRI) involves similar biological processes involved in PM2.5 toxicity and is a known risk factor for CKD. The objective of this study was to investigate the impact of PM2.5 exposure on IRI-induced AKI. Mice were exposed to PM2.5 or filtered air for 12 weeks before IRI, and were euthanized 48h after IRI. Animals exposed to PM2.5 and IRI exhibited reduced glomerular filtration and impaired urine concentration ability. Moreover, they showed elevated tubular damage markers NGAL and KIM-1, along with significant tubular necrosis. PM2.5 exposure exacerbated local innate immune activation, leading to an increased infiltration of Ly6G+ granulocytes and F480+ macrophages in the kidney. This, in turn, contributed to heightened renal senescence markers and myofibroblast infiltration. Collectively, our findings suggest that AKI-induced hampered tubular function is worsened by PM2.5, leading to reduced resilience to stress, activation of aging mechanisms and early hallmarks of fibrosis. Decreasing PM2.5 and implementing preventive strategies can improve AKI patients outcome and prevent AKI progression.