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Acute kidney injury (AKI) is a frequent and severe complication of sepsis and is characterized by significant mortality and morbidity. However, the pathogenesis of septic acute kidney injury (S-AKI) remains elusive. Metabolic reprogramming, which was originally referred to as the Warburg effect in cancer, is strongly related to S-AKI. At the onset of sepsis, both inflammatory cells and renal parenchymal cells, such as macrophages, neutrophils and renal tubular epithelial cells, undergo metabolic shifts toward aerobic glycolysis to amplify proinflammatory responses and fortify cellular resilience to septic stimuli. As the disease progresses, these cells revert to oxidative phosphorylation, thus promoting anti-inflammatory reactions and enhancing functional restoration. Alterations in mitochondrial dynamics and metabolic reprogramming are central to the energetic changes that occur during S-AKI. In this review, we summarize the current understanding of the pathogenesis of metabolic reprogramming in S-AKI, with a focus on each cell type involved. By identifying relevant key regulatory factors, we also explored potential metabolic reprogramming-related therapeutic targets for the management of S-AKI., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Neutrophil-to-lymphocyte ratio (NLR) has been suggested to be a prognostic marker for various diseases, but whether NLR dynamics (ΔNLR) is related to mortality and disease severity in patients with septic acute kidney injury (AKI) has not been determined., Methods: Between August 2013 and August 2021, septic AKI patients at our center were retrospectively enrolled. ΔNLR was defined as the difference between the NLR at septic AKI diagnosis and at hospital admission. The relationship between the ΔNLR and mortality was evaluated by Kaplan-Meier curves, Cox proportional hazards, and cubic spline analyses. The prediction values were compared by area under the receiver-operating characteristic curve (AUROC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) analyses., Results: Of the 413 participants, the mean age was 63 ± 17 years, and 134 were female (32.4%). According to the median value, patients in the high-ΔNLR group had significantly greater 90-d mortality (74.4% vs . 46.6%, p  <  0. 001). After adjustment for potential confounders, high ΔNLR remained an independent predictor of 90-d mortality (HR = 2.80; 95% CI = 1.74-4.49, p  < 0.001). Furthermore, ΔNLR had the highest AUROC for 90-d mortality (0.685) among the various biomarkers and exhibited an improved NRI (0.314) and IDI (0.027) when incorporated with PCT and CRP. For secondary outcomes, patients with high ΔNLR had increased risk of 30-d mortality ( p  = 0.004), need for renal replacement therapy ( p =  0.011), and developing stage-3 AKI (p =  0.040) according to the adjusted models., Conclusions: High ΔNLR is independently associated with increased risk of patient mortality and adverse outcomes. ΔNLR might be utilized to facilitate risk stratification and optimize septic AKI management.

Objective: Sepsis is the leading cause of acute kidney injury (AKI). Increasing evidence shows that serum total protein-to-albumin ratio (TAR) could serve as an inflammation- and nutrition-based prognostic marker in various diseases. The purpose of this study was to assess the prognostic value of TAR in predicting the clinical outcomes of septic AKI patients., Methods: We retrospectively enrolled septic AKI patients between August 2015 and August 2022 at West China Hospital of Sichuan University. Patients admitted between August 2015 and August 2021 were defined as the original cohort. The primary outcomes were 30-day and 90-day all-cause mortality of septic AKI patients. The secondary outcomes were septic shock, transfer to the intensive care unit, mechanical ventilation, requirement for renal replacement therapy, and stage 3 AKI. The utility of TAR was further verified in a validation cohort of septic AKI patients admitted between September 2021 and August 2022., Results: In the original cohort, a total of 309 eligible patients with a median age of 58 years were enrolled, of which 70.2 % were males. In multivariate Cox analysis, after adjustments for age, sex, and other confounding factors, higher TAR at admission was associated with an increased risk of 30-day and 90-day all-cause mortality in septic AKI patients (HR 1.91, 95 % CI 1.18-3.09, P = 0.008; HR 1.54, 95 % CI 1.01-2.34, P = 0.043, respectively). Subgroup analysis revealed no significant interactions in most strata. TAR at AKI diagnosis or discharge was not significantly related to 30-day (P = 0.120 and 0.153, respectively) or 90-day mortality (P = 0.147 and 0.124, respectively). We found no relationship between baseline TAR and septic shock, transfer to the intensive care unit, mechanical ventilation, requirement for renal replacement therapy, or stage 3 AKI (all P > 0.05). In the validation cohort of 81 septic AKI patients, TAR at admission remained a significant prognosticator for 30-day and 90-day mortality (HR 4.367, 95 % CI 1.20-15.87, P = 0.025; HR 4.237, 95 % CI 1.59-11.27, P = 0.004)., Conclusions: TAR at admission is an independent risk factor for 30-day and 90-day mortality in septic AKI patients and could be used as a convenient and economic septic AKI prognostic indicator., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Acute kidney injury (AKI) is a frequent complication of sepsis associated with increased mortality and morbidity. The neutrophil-to-lymphocyte ratio (NLR) has been shown as a risk factor for septic AKI. In this study, we aimed to further evaluate NLR's prediction value on the prognosis of septic AKI patients., Methods: Septic AKI patients at a tertiary university-affiliated medical center were retrospectively enrolled from August 2015 to August 2021. The primary outcomes were 30-day and 90-day mortality, and secondary outcomes were disease severity, length of stay, and rehospitalization in survivors. Kaplan-Meier curves, Cox proportional hazards, cubic spline and logistics regression analyses were performed for adverse outcomes basing on NLR. The predictive value of NLR on morality was also estimated by the area under the receiver operating characteristic curve (AUROC)., Results: A total of 309 septic AKI patients were included with a mean age of 57.8 ± 18.1 years and 92 (29.8 %) being female. The 30-day mortality was 43.4 % and 90-day morality was 61.8 %. When divided by the median of NLR at hospital admission, patients in the high NLR group were associated with an increased 30-day/90-day mortality. After adjusting for multiple covariates, the predictive value of NLR remained significant for 30-day mortality (HR: 2.96, 95 % CI: 1.48-5.92, p = 0.002) and 90-day mortality (HR: 1.88, 95 % CI: 1.11-3.16, p = 0.018). NLR at admission had the highest AUROC (0.618) for 30-day mortality compared with other parameters such as white blood cell (0.573), neutrophil (0.579), lymphocyte (0.567), platelet (0.546), BUN (0.580), albumin (0.545), C-reactive protein (0.571) and procalcitonin (0.534). A similar predictive value on mortality was also observed for NLR measured at septic AKI diagnosis. For secondary outcomes, high NLR was associated with increased risk of transfer to ICU, mechanical ventilation, stage-3 AKI and renal replacement therapy, but not with length of hospital/ICU stay or long-term rehospitalization., Conclusion: High NLR is independently associated with 30-day/90-day mortality and disease severity in septic AKI patients. NLR may serve as an economic and widely available biomarker of septic AKI prognosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)