Abstract
Peroxiredoxin 3 (PRX3) is a mitochondrial antioxidant that regulates apoptosis in various cancers. However, whether tubular PRX3 predicts recovery of renal function following acute kidney injury (AKI) remains unknown. This retrospective cohort study included 54 hospitalized patients who had AKI with biopsy-proven acute tubular necrosis (ATN). The study endpoint was renal function recovery within 6 months. Of the 54 enrolled patients, 25 (46.3%) had pre-existing chronic kidney disease (CKD) and 33 (61%) recovered renal function. Tubular PRX3 expression was higher in patients with ATN than in those without renal function recovery. The level of tubular but not glomerular PRX3 expression predicted renal function recovery from AKI (AUROC = 0.76). In multivariate Cox regression analysis, high PRX3 expression was independently associated with a higher probability of renal function recovery (adjusted hazard ratio = 8.99; 95% CI 1.13–71.52, P = 0.04). Furthermore, the discriminative ability of the clinical model for AKI recovery was improved by adding tubular PRX3. High tubular PRX3 expression was associated with a higher probability of renal function recovery from ATN. Therefore, tubular PRX3 in combination with conventional predictors can further improve recovery prediction and may help with risk stratification in AKI patients with pre-existing CKD.
Highlights
Oxidative stress is an important pathogenic factor of acute kidney injury (AKI), including ischemia-reperfusion injury-induced, sepsis-induced, and nephrotoxin-induced AKI4–7
The present study is the first to identify the up-regulation of Peroxiredoxin 3 (PRX3), an antioxidant mainly localized in the mitochondria, in the glomeruli and renal tubules of patients with acute tubular necrosis (ATN)
The expression level of PRX3 in the renal tubules was positively correlated with baseline eGFR but negatively correlated with urinary protein excretion, tubular atrophy, and interstitial fibrosis
Summary
Oxidative stress is an important pathogenic factor of AKI, including ischemia-reperfusion injury-induced, sepsis-induced, and nephrotoxin-induced AKI4–7. Antioxidant defense systems involving proteins such as nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), glutathione, and heme oxygenase were reported to be altered and have a protective role in AKI7,8. Previous studies using experimental models of AKI have suggested that antioxidants, e.g., N-acetylcysteine, vitamin E, mitoquinone mesylate, or resveratrol, may ameliorate renal injury[9]. Peroxiredoxins (PRXs) are one of the major antioxidants in mammalian cells. Growing evidence suggests that PRX3 may respond to AKI in experimental animal models, the role of PRX3 in patients with AKI remains unclear[17,18]. Little is known about the role of PRX3 in renal tubular injury. In this study, we investigated the expression levels of PRX3 in the kidneys during AKI and examined the association between renal outcome and PRX3 expression after AKI
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