Ferroptosis in tubules has been implicated in the pathogenesis of acute kidney injury (AKI), whereas the regulatory mechanism remains unclear. The stimulator of interferon genes (STING) is previously recognized as a critical mediator of innate immunity via a DNA-sensing pathway and has been increasingly linked to lipid peroxidation, a hallmark of ferroptosis. Herein we investigated the role and the underlying mechanism of STING in AKI models established by ischemia/reperfusion (IR) in C57BL mice. The expression level of STING was predominantly increased in tubules of kidney after IR treatment. Besides, STING deficiency markedly alleviated IR-induced lipid peroxidation, tissue damage and renal dysfunction. Consistently, in vitro experiments demonstrated that the increase in ferroptotic cell death, lipid ROS production and the decrease in GSH peroxidase 4 (GPX4) expression in renal tubular cells subjected to ferroptosis agonist or hypoxia/reoxygenation intervention were all mitigated by genetic deficiency or pharmacological inhibition of STING, while all exacerbated by STING overexpression. Further, these detrimental effects of STING overexpression relied on the induction of ferritinophagy, i.e. autophagic degradation of ferritin, leading to iron overload. Mechanistically, STING mediated the initiation of ferritinophagy through interacting with nuclear receptor coactivator 4 (NCOA4), a fundamental receptor for the transfer of ferritin into lysosome. Collectively, STING contributes to ferroptosis during ischemic AKI through facilitating NCOA4-mediated ferritinophagy and shows the potential as a promising therapeutic choice for AKI.

Introduction: The primary aim of this study was to determine whether hypophosphatemia during continuous veno-venous hemofiltration (CVVH) is associated with the global outcome of critically ill patients with acute kidney injury (AKI). Methods: 760 patients diagnosed with AKI and had received CVVH therapy were retrospectively recruited. Death during the 28-day period and survival at 28 days after initiation of CVVH were used as endpoints. Demographic and clinical data including serum phosphorus levels were recorded along with clinical outcome. Hypophosphatemia was defined according to the colorimetric method as serum phosphorus levels < 0.81 mmol/L (2.5 mg/dL), and severe hypophosphatemia was defined as serum phosphorus levels < 0.32 mmol/L (1 mg/dL). The ratio of CVVH therapy days with hypophosphatemia over total CVVH therapy days was calculated to reflect the persistence of hypophosphatemia. Results: The Cox proportional hazard survival model analysis indicated that the incidence of hypophosphatemia or even severe hypophosphatemia was not associated with 28-day mortality independently (p = 0.700). Further analysis with the sub-cohort of patients who had developed hypophosphatemia during the CVVH therapy period indicated that the mean ratio of CVVH therapy days with hypophosphatemia over total CVVH therapy days was 0.58, and the ratio independently associated with the global outcome. Compared with the patients with low ratio (< 0.58), those with high ratio (≥ 0.58) conferred a 1.451-fold increase in 28-day mortality rate (95% CI 1.103–1.910, p = 0.008). Conclusions: Hypophosphatemia during CVVH associated with the global clinical outcome of critically ill patients with AKI. The ratio of CVVH therapy days with hypophosphatemia over total CVVH therapy days was independently associated with the 28-day mortality, and high ratio conferred higher mortality rate.

Membranous nephropathy (MN), an autoimmune disease, can manifest at any age and is among the most common causes of nephrotic syndrome in adults. In 80% of cases, the specific etiology of MN remains unknown, while the remaining cases are linked to drug use or underlying conditions like systemic lupus erythematosus, hepatitis B virus, or malignancy. Although about one‐third of patients may achieve spontaneous complete or partial remission with conservative management, another third face an elevated risk of disease progression, potentially leading to end‐stage renal disease within 10 years. The identification of phospholipase A2 receptor as the primary target antigen in MN has brought about a significant shift in disease management and monitoring. This review explores recent advancements in the pathophysiology of MN, encompassing pathogenesis, clinical presentations, diagnostic criteria, treatment options, and prognosis, with a focus on emerging developments in pathogenesis and therapeutic strategies aimed at halting disease progression. By synthesizing the latest research findings and clinical insights, this review seeks to contribute to the ongoing efforts to enhance our understanding and management of this challenging autoimmune disorder.

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a major and serious complication in patients undergoing cardiac surgery and is independently associated with perioperative mortality and mortality. Therapeutic intervention aiming at reversing kidney dysfunction seems disappointing across multiple settings. Consequently, attention has shifted from treatment to prevention and early detection. The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines have unified diagnostic standards mainly based on the serum creatinine (Scr) level or urine output, but neither marker is kidney specific. Efforts have been made to identify novel biomarkers with high sensitivity and specificity. The diagnostic capabilities of neutrophil gelatinase-associated lipocalin (NGAL) and G1 cell cycle arrest biomarker as biomarkers have been confirmed in a large number of clinical trials. The utility of biomarkers of cardiac function and inflammation has been validated in clinical studies. Aiming to offer valuable information for further research, we summarize the progress in defining current markers relevant to CSA-AKI in the last three years.

Cardiopulmonary bypass (CPB) is a common technique in cardiac surgery but is associated with acute kidney injury (AKI), which carries considerable morbidity and mortality. In this review, we explore the range and definition of CPB-associated AKI and discuss the possible impact of different disease recognition methods on research outcomes. Furthermore, we introduce the specialized equipment and procedural intricacies associated with CPB surgeries. Based on recent research, we discuss the potential pathogenesis of AKI that may result from CPB, including compromised perfusion and oxygenation, inflammatory activation, oxidative stress, coagulopathy, hemolysis, and endothelial damage. Finally, we explore current interventions aimed at preventing and attenuating renal impairment related to CPB, and presenting these measures from three perspectives: (1) avoiding CPB to eliminate the fundamental impact on renal function; (2) optimizing CPB by adjusting equipment parameters, optimizing surgical procedures, or using improved materials to mitigate kidney damage; (3) employing pharmacological or interventional measures targeting pathogenic factors.

Fibrosis is the common terminal pathway of abnormal tissue repair in various chronic diseases and has become a major global health challenge. Recent research has identified metabolic reprogramming as one of the key factors in the pathogenesis of fibrosis. Lactate, once considered a simple byproduct of glycolysis, has now been confirmed as a crucial metabolic messenger regulating intercellular communication and functional remodeling. The dynamic balance of intercellular lactate shuttling is essential for maintaining tissue homeostasis, and its dysregulation has been closely linked to the progression of fibrosis. Lactylation, a novel post-translational modification driven by lactate accumulation, can regulate protein function and gene expression, thereby playing a significant role in the pathogenesis of fibrosis. In this review, we summarize the latest advancements in the role of lactate and lactylation in the pathogenesis of fibrosis. By integrating the most recent research, we emphasize the importance of lactylation as a potential therapeutic target and explore the translational prospects of targeting lactate metabolism and lactylation in anti-fibrotic treatments, thereby providing novel insights for clinical intervention.