Nanmei Liu

Patients with end-stage renal disease (ESRD) represent a critically ill demographic characterized by complex comorbidities situations and elevated mortality rates [1]. For these individuals, dialys...

Pericyte to myofibroblast transformation is a key driver of renal fibrosis following acute kidney injury (AKI). Exosomes, miRNAs, and bone mesenchymal stem cells (BMSCs) are important in alleviating AKI renal fibrosis. We proposed to explore the role of engineering exosomes rich in miR-145-5p and correlated with KLHL12/KHSRP in AKI-induced pericytes-mediated fibrosis in the present study. Rat perirenal cells were isolated and cultured. Engineering exosomes rich in miR-145-5p derived from BMSCs were obtained through cell transfection technology. AKI rat model and Hypoxia/Reoxygenation (HR) induced perirenal cells injury model were established. Dual luciferase reporter gene, MeRIP, and Co-immunoprecipitation were performed to validate miR-145-5p targeting KLHL12 and its downstream molecules including KHSRP and FLI-1. Renal function, apoptosis and pyroptosis, fibrosis-related proteins were detected through biochemistry, immunohistochemistry, immunofluorescence, and transmission electron microscopy to explore the functional role of the miR-145-5p/ KLHL12/KHSRP/FLI-1 axis in cellular and animal models. According to our findings, pericyte-myoblast transformation contributed to AKI-induced fibrosis in vivo and HR-induced fibrosis along with apoptosis and pyroptosis in vitro. MiR-145-5p down-regulated KLHL12 expression by targeting its 3’UTR to improve perirenal cells-mediated fibrosis. KLHL12 might downregulate KHSRP to increase FLI-1 expression by promoting FLI-1 mRNA stability in AKI-induced fibrosis mediated by perirenal cells. These findings indicate that miR-145-5p enriched in BMSC derived engineered exosomes may suppress KLHL12 expression to up-regulate KHSRP and then down-regulate FLI-1 by m6A to attenuate perirenal cells-mediated fibrosis. Graphical abstract 1. BMSC-derived exosomal miR-145-5p targets KLHL12 in renal pericytes to alleviate AKI-induced fibrosis. 2. miR-145-5p downregulates KLHL12, enhancing KHSRP to promote FLI-1 mRNA decay via m6A modification. 3. This axis inhibits pericyte-to-myofibroblast transition, apoptosis, and pyroptosis, restoring renal function. 4. Engineered miR-145-5p-enriched exosomes offer a promising cell-free therapy for AKI-to-CKD progression. The alternative text for this image may have been generated using AI.

The management of fungal catheter-related bloodstream infections (CRBSIs) in the hemodialysis population represents a critical collision between rigorous infectious disease guidelines and the grim clinical reality of vascular access exhaustion. While guidelines from the IDSA and KDIGO unequivocally recommend immediate catheter removal to prevent metastatic complications, nephrologists are frequently confronted with patients for whom the current catheter represents the last viable lifeline. This review provides a comprehensive analysis of the “catheter salvage” dilemma, moving beyond superficial treatment algorithms to explore the molecular and structural mechanisms that make fungal biofilms a formidable adversary. We dissect the pathogenesis of Candida colonization on abiotic surfaces (silicone and polyurethane), detailing the transition from yeast to hyphal structures and the secretion of a complex extracellular matrix (ECM). We highlight how the ECM, rich in β-1,3 glucan, acts as a physical shield that sequesters azoles, rendering standard systemic therapy ineffective despite in vitro susceptibility. Furthermore, we discuss the role of metabolically dormant “persister cells” in driving high relapse rates and analyze the epidemiological shift toward Candida parapsilosis , a pathogen with a unique affinity for foreign bodies and parenteral nutrition lines. Diagnostically, we scrutinize the limitations of traditional blood cultures and the “Differential Time to Positivity” (DTP) criteria, arguing that the slower growth kinetics of fungi render DTP unreliable compared to bacterial infections. The core of this review evaluates the efficacy and safety of Antifungal Lock Therapy (ALT) as a bridging strategy. We provide a comparative analysis of lock agents, contrasting the broad lytic potential of ethanol (the “nuclear option”) with the safety profile of taurolidine and the pharmacological nuances of amphotericin B and echinocandins. Ultimately, we propose that while catheter removal remains the gold standard, a nuanced mastery of biofilm biology and lock therapy protocols is essential for managing complex, access-challenged patients where immediate removal is not feasible.

1. CKD-aP, a form of pruritus directly attributable to kidney dysfunction and not associated with other comorbid conditions, represents a prevalent and burdensome symptom among patients with ESKD. ...

Chronic kidney disease-associated pruritus (CKD-aP) is a common complication in patients with end-stage kidney disease (ESKD) that seriously affects quality of life. Its pathogenesis is complex, involving toxin accumulation, immune dysregulation, nerve conduction changes, and other factors, but its relationship with skin barrier function has not been widely studied. From the perspective of skin barrier damage, this article systematically elaborates on the structure and function of the skin barrier, the pathological changes of the skin barrier in uremic patients, and its mechanism in the occurrence of pruritus, and analyses in detail how the pathological changes lead to the generation and maintenance of pruritus. In addition, this review also presents the treatment strategies for CKD-aP for skin barrier repair, which provides a novel therapeutic insight.

Fibroblast Growth Factor 23 (FGF23) is a bone-derived hormone regulating phosphate and vitamin D metabolism, now recognized as a dynamic biomarker across acute and chronic kidney disorders. Elevated FGF23 is a hallmark of chronic kidney disease (CKD), but also rises acutely in acute kidney injury (AKI) and appears disproportionately high in autosomal dominant polycystic kidney disease (ADPKD), underscoring condition-specific regulation. This review explores the correlation and heterogeneity of FGF23 expression in AKI, CKD, and ADPKD, highlighting shared and divergent mechanisms and the diagnostic and therapeutic implications. We summarize FGF23 expression kinetics in each condition, elucidate known and proposed molecular drivers of its elevation, and discuss how FGF23 serves as a unifying yet disease-divergent marker in renal pathology. In AKI, inflammation, ischemia, and acute metabolic stress drive a rapid FGF23 surge, whereas in CKD, phosphate retention and Klotho deficiency promote a sustained, maladaptive FGF23 elevation. ADPKD shows early FGF23 increases independent of glomerular filtration rate (GFR), potentially due to ectopic production (liver and cysts) and unique tubular defects. Clinically, FGF23 has emerged as an indicator of disease severity and outcomes in these contexts: it can signal early AKI and predict progression, is a strong prognostic factor for mortality and cardiovascular complications in CKD, and correlates with cystic disease burden and kidney growth in ADPKD. We also examine FGF23’s systemic effects (notably on cardiovascular remodeling) and potential therapeutic targets, from modulating phosphate balance and iron metabolism to novel interventions in development. Understanding the nuanced regulation of FGF23 across acute injury, chronic degeneration, and genetic kidney disease provides insight into acute-chronic disease intersections and guides precision diagnostics and therapies for improved patient outcomes.

Paraquat (PQ) poisoning has a high mortality rate due to rapid systemic distribution and oxidative organ damage, particularly in the lungs. Conventional therapies are often inadequate, prompting interest in extracorporeal therapies to enhance PQ clearance. This narrative review synthesizes current evidence on hemoperfusion (HP), continuous renal replacement therapy (CRRT), hemodiafiltration (HDF), haemodialysis (HD) and therapeutic plasma exchange (TPE) in PQ poisoning. Studies were evaluated for therapeutic mechanisms, clinical outcomes and optimal implementation strategies. Early and repeated HP, especially within 4-6 h post-ingestion, improves survival by directly adsorbing PQ. CRRT supports renal function and facilitates sustained toxin removal, with the best outcomes observed when combined with HP. HDF allows prolonged clearance but has limited supporting data. HD, while useful for managing acute kidney injury, appears ineffective for PQ elimination and may increase mortality. TPE shows potential benefits in severe cases if administered early, but evidence is limited to small studies. Combination therapies (e.g. HP with CRRT or HD) demonstrate synergistic effects in improving survival and organ support. Extracorporeal therapies, particularly early HP and HP combined with CRRT, are promising strategies in PQ poisoning. HD should not be the primary detoxification method but remains important for supportive care. TPE may be beneficial in selected cases. Further randomized trials are needed to optimize treatment protocols and validate combined approaches.

Introduction: Anti-glomerular basement membrane (anti-GBM) disease is a rare autoimmune vasculitis that often leads to rapidly progressive glomerulonephritis and poor renal prognosis. Standard treatment typically involves plasmapheresis, corticosteroids, and cyclophosphamide. However, the therapeutic role of obinutuzumab, a B-cell-depleting monoclonal antibody, remains under-explored in anti-GBM disease. Case Presentation: We report a 20-year-old male with isolated renal anti-GBM disease following a dental infection, who presented with severe acute kidney injury (creatinine >700 μmol/L), high anti-GBM antibody titers, and crescentic glomerulonephritis on biopsy. Despite initial therapy with plasmapheresis, corticosteroids, and cyclophosphamide, renal function deteriorated. Obinutuzumab (500 mg IV) was administered as adjunct therapy, leading to rapid antibody clearance within 1 month. Remarkably, the patient achieved partial renal recovery and was dialysis-independent by 3 months, with stable stage 3 chronic kidney disease at 5-month follow-up. Conclusion: This case underscores the potential role of obinutuzumab as an innovative adjunctive therapy in severe anti-GBM disease, even in patients with traditionally poor prognostic markers. Early and aggressive multimodal treatment, including B-cell targeting, may improve outcomes in selected cases.

Ischemia–reperfusion injury (IRI) is one of the pathogenic factors of acute kidney injury (AKI). Anostosis, including apoptosis, proptosis, necroptosis, along with ferroptosis and autophagy, is involved in IRI. Based on bioinformatics analysis, we aimed to explore the effect of Ubiquitin Conjugating Enzyme E2 C/Pituitary Tumor‐Transforming Gene 1 on renal IRI in the present study. The IRI model in vitro and in vivo was established; correlation of UBE2C with PTTG1, including ubiquitination through down and over‐expression of UBE2C/PTTG1 construction in IRI‐induced AKI was investigated. Our results indicated that IRI‐induced increasing UBE2C/PTTG1 expression at 3 days reperfusion and decreased gradually at 7 days to 14 days after ischemia. Down expression of UBE2C/PTTG1 promoted apoptosis and ferroptosis while suppressing autophagy in the IRI‐induced kidney. The effect of UBE2C may be reversed by intervention on PTTG1 expression, and UBE2C regulated PTTG1 expression by affecting its ubiquitination. Our results suggested that UBE2C might promote PTTG1 expression by enhancing its stability through decreasing ubiquitination to inhibit Panopolis and ferroptosis while facilitating autophagy to protect the kidney from IR‐induced AKI.