Junhua Li

Dialysis-dependent chronic kidney disease (DD-CKD), a severe form of end-stage renal disease (ESRD), currently affects more than three million patients globa... Dialysis-dependent chronic kidney disease (DD-CKD), a severe form of end-stage renal disease (ESRD), currently affects more than three million patients globa...

Cardiorenal syndrome (CRS) is a complex clinical and pathological condition characterized by the dysfunction of either the heart or the kidney, leading to subsequent dysfunction in the other organ in the context of acute or chronic functional impairment. Given the escalating incidence and mortality rates of CRS particularly against the backdrop of an aging population and the rising prevalence of cardiovascular diseases, underscore the need for a deeper understanding of its underlying pathogenesis. Recently, the role of mineralocorticoid receptors (MR) in CRS has garnered significant research attention. Evidence suggests that aberrant activation of MR not only disrupts water and sodium homeostasis, resulting in abnormal blood volume expansion, but also triggers inflammatory responses, tissue fibrosis, and hyperactivation of the sympathetic nervous system and renin-angiotensin-aldosterone system. These intricate pathophysiological processes exert profound negative impacts on cardiac and renal functions. Finerenone, a novel non-steroidal selective mineralocorticoid receptor antagonist (MRA), has demonstrated significant therapeutic potential and unique pharmacological mechanism in the treatment of cardiorenal syndrome, especially chronic kidney disease (CKD) associated with type 2 diabetes mellitus (T2DM) in recent years. In this review, we summarize the mechanisms by which finerenone interacts with MR and its promising therapeutic role in cardiorenal syndrome.

Diabetic kidney disease (DKD) has emerged as the leading cause of chronic kidney disease (CKD) worldwide, surpassing primary glomerular disorders in prevalence. Despite recent therapeutic advances, current treatment strategies primarily alleviate symptoms rather than address the underlying pathogenic mechanisms, highlighting an urgent need for targeted, mechanism-based interventions. The pathogenesis of DKD involves a complex interplay of metabolic, hemodynamic, inflammatory, oxidative, and fibrotic pathways. Chronic hyperglycemia initiates a cascade of molecular events—including the accumulation of advanced glycation end products (AGEs), activation of the polyol pathway, enhanced protein kinase C (PKC) signaling, and mitochondrial dysfunction—culminating in glomerular hyperfiltration, podocyte injury, and progressive glomerular and tubulointerstitial fibrosis. In addition to these classical mechanisms, emerging processes such as ferroptosis (iron-dependent cell death), impaired autophagy, gut microbiota dysbiosis, and epigenetic alterations offer promising therapeutic targets. Current DKD management integrates lifestyle modifications with four cornerstone pharmacologic classes: renin–angiotensin–aldosterone system inhibitors (RAASi), sodium–glucose co-transporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and mineralocorticoid receptor antagonists (MRAs). Notably, evidence from clinical trials suggests that simultaneous modulation of multiple pathogenic pathways provides superior cardiorenal protection compared to monotherapy. Investigational therapies—including endothelin receptor antagonists (ERAs), nuclear factor erythroid 2–related factor 2 (Nrf2) activators, and gut microbiota modulators—are under active evaluation. Additionally, Traditional Chinese Medicine (TCM) formulations have demonstrated albuminuria-lowering effects in clinical studies. Future research should prioritize biomarker-driven precision medicine approaches, enabling individualized therapy selection and development of agents that concurrently target ferroptosis and inflammation. Given the multifaceted pathophysiology of DKD, optimal management will require multimodal, patient-tailored regimens that address hyperglycemia, hypertension, inflammation, and fibrosis to effectively slow or halt disease progression.

Currently, the field of tumor nephrology continues to evolve, and the interplay between chronic kidney disease (CKD) and lymphoma merits further investigation. The incidence of CKD among lymphoma patients is substantial, posing a significant long-term risk for CKD progression. CKD should be regarded as an independent prognostic factor for mortality in lymphoma patients. In this mini-review, we aim to extend the research direction outlined in "Diagnosis and Treatment of Secondary Nephrotic Syndrome with Rash as the Initial Symptom: A Case Report", with a focus on elucidating the correlation between CKD and lymphoma. Specifically, we will examine the onset characteristics, renal pathological changes, survival prognosis, and renal toxicity associated with various therapeutic regimens. This investigation may provide valuable insights for optimizing medical management and improving long-term outcomes in this patient population.

Objectives: Previous research has demonstrated associations between various inflammatory cytokines and IgA nephropathy (IgAN). However, the causal relationships between them remain unclear. The purpose of this study is to extensively analyze the causal links between 91 circulating cytokines and IgAN. Methods: This study commenced with a two‐sample bidirectional Mendelian randomization analysis. Genetic variations associated with 91 circulating inflammatory cytokines were extracted from genome‐wide association study (GWAS) data involving individuals of European ancestry ( n = 14824). In the corresponding GWAS dataset, the genetic variations for IgAN were obtained from a Finnish cohort of European ancestry, consisting of a case group ( n = 653) and a control group ( n = 411528). The findings from the Mendelian randomization analysis were subsequently subjected to preliminary validation using the GSE116626 dataset from the GEO database. Results: Our MR analysis indicates that transforming growth factor‐alpha (TGF‐alpha), leukemia inhibitory factor (LIF), and C–C motif chemokine 19 (CCL19) are linked to an increased risk of IgAN. There were no causal connections found when IgAN was used as an exposure and the 91 circulating inflammatory cytokines as outcomes. In addition, the GSE116626 dataset from the GEO database revealed significant upregulation of CCL19 in renal tissues from patients diagnosed with IgAN. Conclusions: This study shows a causal link between inflammatory cytokines and IgAN, suggesting that TGF‐alpha, LIF, and CCL19 may act as upstream mediators in the pathogenic pathways of IgAN. The critical role of CCL19 in the pathogenesis of IgAN was further validated using data from the GEO database. However, whether these cytokines can be used to predict or ameliorate the progression of IgAN requires further investigation.

Acute kidney injury (AKI) is a significant issue in public health, displaying a high occurrence rate and mortality rate. Ferroptosis, a form of programmed cell death (PCD), is characterized by iron accumulation and intensified lipid peroxidation. Recent studies have demonstrated the pivotal significance of ferroptosis in AKI caused by diverse stimuli, including ischemia-reperfusion injury (IRI), sepsis and toxins. Autophagy, a multistep process that targets damaged organelles and macromolecules for degradation and recycling, also plays an essential role in AKI. Previous research has demonstrated that autophagy deletion in proximal tubules could aggravate tubular injury and renal function loss, indicating the protective function of autophagy in AKI. Consequently, finding ways to stimulate autophagy has become a crucial therapeutic strategy. The recent discovery of the role of selective autophagy in influencing ferroptosis has identified new therapeutic targets for AKI and has highlighted the importance of understanding the cross-talk between autophagy and ferroptosis. This study aims to provide an overview of the signaling pathways involved in ferroptosis and autophagy, focusing on the mechanisms and functions of selective autophagy and autophagy-dependent ferroptosis. We hope to establish a foundation for future investigations into the interaction between autophagy and ferroptosis in AKI as well as other diseases.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease categorized as antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis. The majority of patients are ANCA‐positive, predominantly against myeloperoxidase (MPO). Previous studies have predominantly concentrated on the association between EGPA and neutrophils, but recent research has emphasized the role of lymphocytes in the development of EGPA. The objective of our research was to examine the causal association between immune cells and MPO + ANCA EGPA. A two‐sample bidirectional Mendelian randomization (MR) analysis was performed, which included 159 MPO + ANCA EGPA cases and 6688 controls and utilized Genome‐Wind Associaton Studies (GWAS) summary statistics of immune traits from approximately 3757 individuals, encompassing around 22 million single nucleotide polymorphisms (SNPs). Our findings revealed that 23 immunophenotypes were associated with MPO + ANCA EGPA. Furthermore, the reverse MR analysis showed that MPO + ANCA EGPA had significant causal effects on three immunophenotypes within the Treg panel. By integrating existing research, our study unveiled the contributions of Tregs, B cells, and monocytes to the development of EGPA. Subgroup analysis specifically examined the roles of lymphocyte subtypes, cytokines, and their surface molecules in the pathogenic mechanisms of the disease. This comprehensive approach provides a novel perspective on the biological mechanisms and early intervention strategies for MPO + ANCA EGPA by focusing on immune cells.

Background: Membranous nephropathy (MN) is a common type of nephrotic syndrome (NS) in adults, accounting for about 20–30% of cases. Although secondary to specific factors, the coexistence of MN and mantle cell lymphoma (MCL) has been scarcely reported in clinical literature. Case presentation: A 59-year-old Chinese male was admitted to the hospital with a generalized pruritic rash with bilateral lower extremity edema, which did not improve significantly after symptomatic treatment. He had undergone renal biopsy, and the diagnosis was thought to be secondary MN (SMN), therefore, we did a lymph node biopsy on the patient and found that MN was complicated with MCL. Soon after, the patient was admitted to the hematology department for a BR chemotherapy regimen (composed of bendamustine 90 mg/m² BSA (body surface area), rituximab 375 mg/m² BSA and dexamethasone 5 mg), and during the post-treatment follow-up, both his symptoms and renal function improved. Conclusions: The mechanism underlying the combination of SMN and MCL remains elusive and exceedingly rare, consequently often overlooked in clinical practice. This case serves to offer valuable clinical insights for diagnosis and treatment, while emphasizing the pivotal role of renal pathology in clinical assessment.

Dexamethasone (DEX), a ligand for glucocorticoid receptor (GR), has long been used in the clinical practice due to its anti-inflammatory and immunosuppressive properties. Given that ischemia/reperfusion (IR)-induced renal injury is featured by the excessive immune response; the current study is therefore designed to address the impact of dexamethasone on IR-induced renal injury, a common disorder in the clinical settings. Precondition of mice with 4 mg/kg of dexamethasone significantly attenuated IR-induced injury as manifested by the improved renal function along with ameliorated pathological changes and suppressed inflammatory infiltration. Mechanistic studies revealed that dexamethasone promotes GR activation, and by which it attenuates the signals for PI3K/AKT activation. Attenuated PI3K/AKT signaling thus suppresses inflammatory response which then protects kidneys from IR-induced injury. All together, our data support that dexamethasone could be a good alternative therapy for prevention and treatment of IR-induced renal injury in the clinical practice.