Ferroptosis is a non-traditional form of regulated cell death, characterized by iron overload and lipid peroxidation. Exploration of ferroptosis in chronic kidney disease (CKD) has been extremely limited to date. In this study, we established a rat model of CKD by 5/6 nephrectomy, treated CKD rats with the ferroptosis inducer, cisplatin (CDDP), and the ferroptosis inhibitor, deferoxamine mesylate (DFO), and observed the resulting pathologic changes (injury markers and fibrosis) and ferroptotic biochemical indices. Kidney iron deposition, lipid peroxidation, mitochondrial defects, ferroptosis marker induction, and TUNEL staining positivity were detected in CKD group rats. Further, treatment with CDDP or DFO influenced renal injury and fibrosis by affecting ferroptosis, rather than apoptosis, and ferroptosis occurs in the remnant kidney due to disordered iron metabolism. In conclusion, our study shows for the first time that 5/6 nephrectomy induces ferroptosis in the remnant kidney and clarifies the underlying pathogenesis. Moreover, we demonstrate that ferroptosis is involved in CKD progression and represents a therapeutic target in chronic kidney injury and renal fibrosis.

Purpose. We aimed to explore the relationship between the cardiometabolic index (CMI) and cardiovascular disease (CVD) and its subtypes (coronary artery disease and stroke) in patients with hypertension and obstructive sleep apnea (OSA). Methods. We conducted a retrospective cohort study enrolling 2067 participants from the Urumqi Research on Sleep Apnea and Hypertension study. The CMI was calculated as triglyceride to high ‐ density   lipoprotein   cholesterol   ratio × waist ‐ to ‐ height   ratio . Participants were divided into three groups (T1, T2, and T3) according to the tertile of CMI. The Kaplan-Meier method helped to calculate the cumulative incidence of CVD in different groups. We assessed the association of CMI with the risk of CVD and CVD subtypes by estimating hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox models. Results. During a median follow-up of 6.83 years (interquartile range: 5.92-8.00 years), 326 incident CVD were identified, including 121 incident stroke and 205 incident coronary heart disease (CHD). Overall, after adjusting for confounding variables, CMI was positively associated with the risk of new-onset CVD (per SD increment, adjusted HR: 1.31; 95% CI: 1.20, 1.43), new-onset CHD (per SD increment, adjusted HR: 1.33; 95% CI: 1.20, 1.48), and new-onset stroke (per SD increment, adjusted HR: 1.27; 95% CI: 1.10, 1.47). Similar results were obtained in various subgroup and sensitivity analyses. Adding CMI to the baseline risk model for CVD improved the C -index ( P < 0.001 ), continuous net reclassification improvement ( P < 0.001 ), and integrated discrimination index ( P < 0.001 ). Similar results were observed for CHD and stroke. Conclusion. There was a positive association between CMI levels and the risk of new-onset CVD in patients with hypertension and OSA. This finding suggests that CMI may help identify people at high risk of developing CVD.

Ferroptosis is a type of programmed cell death characterized by iron overload, oxidative stress, imbalance in lipid repair, and mitochondria-specific pathological manifestations. Growing number of molecular mechanisms and signaling pathways have been found to be involved in ferroptosis progression, including iron metabolism, amino acid metabolism, lipid metabolism, and energy metabolism. It is worth noting that ferroptosis is involved in the progression of fibrotic diseases such as liver cirrhosis, cardiomyopathy, and idiopathic pulmonary fibrosis, and inhibition of ferroptosis has acquired beneficial outcomes in rodent models, while studies on ferroptosis and renal fibrosis remains limited. Recent studies have revealed that targeting ferroptosis can effectively mitigate chronic kidney injury and renal fibrosis. Moreover, myofibroblasts suffer from ferroptosis during fiber and extracellular matrix deposition in the fibrotic cascade reaction and pharmacological modulation of ferroptosis shows great therapeutic effect on renal fibrosis. Here, we summarize the latest molecular mechanisms of ferroptosis from high-quality studies and review its therapeutic potential in renal fibrosis.

Objectives This study aimed to investigate the distribution patterns and research frontiers of international literature and thus present a holistic bibliometric evaluation of the studies on IgA nephropathy. Methods The Web of Science Core Collection database was searched for studies of IgA nephropathy from January 2012 to March 2023. The keywords and references are analyzed by CiteSpace, while the countries and institutions are analyzed by VOSviewer. Results A total of 2987 publications on IgA nephropathy were included. The country with the most publications was China ( n = 1299), and the institution with the most publications was Peking University ( n = 139). The most frequent keywords were IgA nephropathy ( n = 2013), Oxford classification ( n = 482), and diseases ( n = 433). The keywords that continue to burst out at high intensity are multicenter study and gut microbiota. Moreover, the top five references for burst strength were also listed. Conclusions IgA nephropathy has attracted widespread research interest, particularly in high-prevalence areas. From 2012 to 2023, publications on IgA nephropathy show a linear increase. China is the country with the highest number of publications and Peking University is the institution with the highest number of publications. Current research hotspots and frontiers are mainly multicenter studies related to IgA nephropathy and its exploration with gut microbiota. Overall, we have provided a comprehensive scientometric analysis of IgA nephropathy that will inform researchers and healthcare practitioners. Supplementary Information The online version contains supplementary material available at 10.1007/s11255-023-03598-x.