Acute kidney injury (AKI), a life-threatening disorder marked by abrupt renal dysfunction, is increasingly recognized as a global healthcare challenge. It not only triggers immediate organ dysfunction but also heightens long-term risks of chronic kidney disease (CKD). The senescence of proximal tubular epithelial cells (PTECs) has a major impact on the occurrence and development of AKI. This review systematically analyzes existing evidence, which suggests that the senescence of PTECs may have a dual effect. Acute cellular senescence typically mitigates uncontrolled replication of damaged cells by inducing cell cycle arrest, thereby limiting the further expansion of tissue damage. In contrast, the pathological retention of chronic senescent cells and the excessive production of the senescence-associated secretory phenotype (SASP) exacerbate the local inflammatory response and the process of fibrosis, accelerating the transformation of AKI into CKD. Despite incomplete elucidation of the spatiotemporal mechanisms governing the transition from acute to chronic cellular senescence, therapeutic interventions can be precisely targeted to specific disease stages based on their characteristic progression dynamics. This review summarizes the intervention strategies applicable at different stages of AKI, including prevention, early induction of senescence, senoreverse, senolysis, and senomorphics. Additionally, we highlight potential therapeutic targets to provide a theoretical basis for optimizing clinical management.

BACKGROUND:Idiopathic membranous nephropathy (IMN) is a major cause of nephrotic syndrome and end-stage renal disease, but the gold-standard diagnostic method is invasive. This study aims to develop a non-invasive diagnostic model for IMN, focus on the diagnostic value of anti-phospholipase A2 receptor antibody (anti-PLA2R-Ab). PATIENTS AND METHODS:In this single-center retrospective study,we included 9524 patients with chronic kidney disease patients who received renal biopsies, extracted 139 clinicopathological data from their records, and divided them into two groups based on pathological results.Renal biopsy cases were collected to form an independent external validation cohort.Seven machine learning methods were used to develop and verify models, and anti-PLA2R-Ab data were used to optimize and evaluate these models. Seventy percent of the patients were used for training, and the other 30% for verification. The area under the receiver operating characteristic curve, F1-score, accuracy, and confusion matrix were used to evaluate the diagnostic performance of the models. RESULTS:We analyzed 8840 patients and 10 indicators, excluding anti-PLA2R-Ab, to develop and validate diagnostic models, and then analyzed 2457 patients and 6 indicators, including anti-PLA2R-Ab, to develop and validate optimized models. With or without anti-PLA2R-Ab, the CatBoost model provided more accurate diagnosis of IMN (internal vs. external verification AUC:0.921 vs.0.901 and 0.950 vs.0.904, respectively) than anti-PLA2R-Ab alone (AUC: 0.867). CONCLUSION:The CatBoost model was an accurate and non-invasive method that provided better diagnosis of IMN than anti-PLA2R-Ab in Chinese patients. This model is especially when anti-PLA2R-Ab testing and kidney biopsy are difficult or impossible.

The relationship between kidney function and mortality in centenarians, particularly with respect to hormonal regulation, remains unclear. This study investigated the association between estimated glomerular filtration rate (eGFR) and all-cause mortality in female centenarians and explored the potential role of testosterone. Within the China Hainan Centenarian Cohort Study, 701 female centenarians (median age: 102 years) were enrolled. eGFR was calculated using the CKD-EPI 2009 creatinine equation. Restricted cubic splines (RCSs) and multivariable Cox proportional hazards models were employed to assess nonlinear associations. Likelihood ratio tests were used to evaluate the interaction effect of testosterone. During a median follow-up of 31 months, 643 participants (91.7

BACKGROUND:During the progression of immunoglobulin A nephropathy (IgAN), residual nephrons compensate for nephron loss by increasing single-nephron estimated glomerular filtration rate (eGFR). This adaptive hyperfiltration may accelerate the decline in kidney function. However, due to measurement challenges, the prognostic value of single-nephron eGFR remains unclear. This study investigates its impact on kidney function decline in patients with IgAN. METHODS:This observational cohort study included 187 biopsy-confirmed IgAN patients who had undergone computed tomography and biopsy during their hospitalization. Single-nephron eGFR was estimated by dividing total eGFR by nephron number, the latter of which was derived from the cortical volume and glomerular density. The primary composite outcome was kidney function decline, defined as a sustained annual eGFR decrease of ≥5 mL/min/1.73 m2, a ≥40% reduction in eGFR from baseline or end-stage renal disease. Cox proportional hazards models were fit to estimate associations between single-nephron eGFR and kidney function decline. RESULTS:Among the 187 participants (45% women, mean age 38 ± 11 years), 57 experienced a decline in kidney function over a median follow-up period of 3.1 years. Participants were divided into three groups based on their single-nephron eGFR. Kaplan-Meier analysis demonstrated significantly reduced kidney survival in the high single-nephron eGFR group compared with the low and middle groups (log-rank P < .001). Compared with the low single-nephron eGFR group, multivariable hazard ratios for kidney function decline were 2.50 (95% confidence interval 1.10-5.67; P = .03) for the middle group and 5.30 (2.44-11.54; P < .001) for the high group. CONCLUSIONS:A higher single-nephron eGFR is identified as a risk factor for kidney function decline in patients with IgAN, which supports its potential as an early risk-stratification tool. Moreover, using eGFR cutoffs alone to define hyperfiltration may lead to misclassification due to its inability to distinguish patients with hyperfiltration from those without.

Abstract Objectives To validate blood oxygen level-dependent MRI (BOLD-MRI) for non-invasive discrimination of diabetic nephropathy (DN) vs non-diabetic renal disease (NDRD) and prediction of end-stage renal disease (ESRD) in diabetic kidney disease (DKD). Materials and methods A prospective cohort of 133 biopsy-proven DKD patients underwent BOLD-MRI. The semi-automated 12-layer concentric-objects method was used to analyze BOLD-MRI variables. Prognostic markers for ESRD were identified using univariate and multivariate Cox regression. Feature importance was used to select key diagnostic variables and establish logistic regression and machine-learning differential diagnosis models. Results Among 133 patients (44 DN, 55 NDRD, 34 combined), 20 (15.5%) progressed to ESRD over a mean of 21.8 months. Higher renal medullary R2* (MR2*) (> 24 1/s) reduced ESRD risk by 52% (HR, 0.48) in DKD. Prognostic models integrating pathological grouping, hemoglobin levels, and cysC levels achieved a c-index of 0.90. For the DN and combined groups, MR2*, glomerular grading, interstitial lesions, interstitial fibrosis, and tubular atrophy were predictive of ESRD, with a c-index of 0.91. For differential diagnosis, the random forest (RF) model achieved an AUC of 0.901, with diabetic retinopathy, diabetes duration, albumin, blood urea nitrogen, MR2*, hypertension, and glycosylated hemoglobin as the most contributing factors. For the combined group classified as DN, the AUC of the RF model was 0.791; when classified as NDRD, the AUC was 0.856. Conclusion MR2* shows potential value as a non-invasive diagnostic and prognostic tool in the assessment of DKD. However, BOLD-MRI remains a promising yet exploratory technique that requires external validation and interventional studies before clinical implementation. Critical relevance statement Blood oxygen level-dependent-MRI-derived renal medullary R2* robustly predicts ESRD risk and distinguishes DN without biopsy, offering an immediately translatable, non-invasive biomarker for the precision management of DKD in routine nephrology practice. Trial registration ClinicalTrials.gov, NCT03865914. Key Points Blood oxygen level-dependent-MRI medullary R2*(MR2*) > 24 s− 1 halves DKD ESRD risk (HR 0.48). MR2* integrated with clinical variables drives c-index to 0.90 for ESRD prognosis. RF leveraging MR2* and clinical traits attains an AUC of 0.901 for diagnosing DN. Graphical Abstract

Importance:Glomerular diseases are a leading cause of chronic kidney disease (CKD) and kidney failure. Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, reduces the risk of kidney function loss in CKD, but its effects in individuals with CKD due to glomerular diseases are uncertain. Objectives:To evaluate the efficacy and safety of finerenone in patients with glomerular diseases. Design, Setting, and Participants:Prespecified exploratory subgroup analysis of a phase 3, randomized, double-blind, placebo-controlled trial conducted across 24 countries and regions, focusing on participants with an investigator-reported glomerular disease diagnosis. The overall trial enrolled adults with nondiabetic CKD and an estimated glomerular filtration rate (eGFR) of either (1) at least 25 to less than 60 mL/min/1.73 m2 and urinary albumin to creatinine ratio of at least 200 mg/g to less than 500 mg/g or (2) an eGFR of at least 25 to less than 90 mL/min/1.73 m2 and urinary albumin to creatinine ratio of at least 500 mg/g to less than 3500 mg/g. Intervention:Finerenone 10 mg or 20 mg taken orally once daily (n = 446) vs matching placebo (n = 457). Main Outcomes and Measures:Annualized rate of eGFR decline (total eGFR slope) from baseline to month 32 (primary outcome of the main trial); percent change in albuminuria to 12 months; and a composite outcome of kidney failure or sustained 40% or more decline in eGFR (prespecified exploratory outcomes). Results:Of 1584 participants, 903 (57.0%) had investigator-reported glomerular disease, including 416 (46.1%) with immunoglobulin A nephropathy, 215 (23.8%) with focal segmental glomerulosclerosis, and 90 (10.0%) with membranous nephropathy. Participants with glomerular disease (mean [SD] age, 51.1 [13.6] years; 362 female [40.1%]; 558 Asian [61.9%]) had a mean eGFR of 48.8 mL/min/1.73 m2 and median urinary albumin to creatinine ratio of 839.6 mg/g. The total eGFR slope up to 32 months was -3.50 mL/min/1.73 m2 per year with finerenone and -4.23 mL/min/1.73 m2 per year with placebo (0.73 mL/min/1.73 m2 per year difference; 95% CI, 0.22-1.24). Finerenone reduced albuminuria at month 12 by 42% (95% CI, 35%-48%) and lowered the risk of kidney failure or 40% or more eGFR decline (7.42 vs 9.60 events per 100 patient-years; hazard ratio, 0.74; 95% CI, 0.57-0.97). Conclusions and Relevance:In this exploratory analysis, treatment with finerenone slowed kidney function decline, reduced albuminuria, and lowered the risk of kidney failure or substantial loss of kidney function in patients with glomerular diseases. These findings suggest an important role for finerenone in preserving kidney function in this population. Trial Registration:ClinicalTrials.gov Identifier: NCT05047263.

The extent of the inflammatory response in the early stages of acute kidney injury (AKI) significantly influences renal damage, repair, and ultimately prognosis. Macrophages are key drivers of early inflammation in AKI, and their metabolic reprogramming is closely associated with their pro-inflammatory polarization. However, the mechanisms underlying this process remain incompletely understood. In this study, we combined single-cell RNA sequencing, metabolomics, and gene-editing approaches to, investigate how injured renal tubular epithelial cells regulate macrophage metabolism and phenotype in ischemia-reperfusion injury (IRI)-induced AKI. We found that injured proximal tubular cells secrete high levels of secreted phosphoprotein 1 (SPP1), which binds to CD44, a receptor abundantly expressed on infiltrating macrophages, thereby activating the downstream PI3K/AKT signaling pathway. This activation induces nuclear translocation of PKM2, a key metabolic enzyme, which drives glycolytic metabolic reprogramming in macrophages and promotes their polarization toward a pro-inflammatory phenotype. In vitro and in vivo functional experiments further confirmed that blocking the SPP1-CD44 axis, using siRNA, neutralizing antibodies, or conditional knockout strategies, effectively alleviates renal IRI in mice, reduces macrophage infiltration, and diminishes the inflammatory response. Overall, this study delineates a novel mechanism in which injured tubular cell-derived SPP1 communicates with macrophage CD44 to regulate immunometabolism and inflammatory polarization via the PI3K/AKT-PKM2 signaling module at the single-cell and metabolic levels. These findings provide both a potential therapeutic target and a mechanistic framework for the prevention and treatment of AKI.

SGLT2 inhibitors are widely recommended by clinical guidelines for managing diabetes, cardiovascular, and kidney diseases. High glucose induces proximal tubular epithelial cell senescence and epithelial-mesenchymal transition (EMT), promoting renal interstitial fibrosis. However, the impact of SGLT2 inhibitor-induced hyperglucosuria on distal tubular cell biology remains unreported. C57BL/6 or db/db mice were administered empagliflozin via oral gavage for 4 weeks. Tissues were collected post-intervention to assess the immediate effects on distal tubular cell senescence and EMT. After treatment cessation, C57BL/6 and db/db mice were maintained for another 24 and 11 weeks respectively to investigate subsequent effects. In vitro, mouse distal convoluted tubule (mDCT) cells were stimulated with high glucose to verify mechanisms of glucose-induced senescence and EMT. Empagliflozin induced hyperglucosuria that persisted post-cessation. In C57BL/6 mice, immediate effects led to senescence marked by CDKN1A upregulation and EMT in distal tubular cells. Twenty-four weeks post-cessation, these cells exhibited senescence with co-upregulation of CDKN2A and CDKN1A, EMT progression, and renal interstitial fibrosis. In db/db mice, immediate effects did not exacerbate senescence or EMT, but 11 weeks post-cessation aggravated senescence, EMT progression, and renal interstitial fibrosis. In vitro, high glucose promoted reactive oxygen species (ROS) generation, exacerbated DNA damage, and induced mDCT cell senescence and EMT by upregulating CDKN2A. This study first demonstrates that persistent SGLT2 inhibitor-induced hyperglucosuria drives distal tubular cell senescence, EMT, and renal interstitial fibrosis in wild-type and db/db mice, providing foundational evidence for a more comprehensive understanding of these drugs.

Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) that significantly increases the risk of progression to chronic kidney disease (CKD). Although oxidative stress has been implicated in this transition, the precise mechanisms through which it orchestrates inflammation and fibrosis during IRI-induced AKI-CKD progression remain poorly understood. In this study, we observed sustained reactive oxygen species (ROS) production in post-IRI kidneys. ROS were found to activate AMP-activated protein kinase (AMPK) in macrophages in a calcium-dependent manner. Conditional knockout of AMPKα1 in macrophages (Lyz2-Cre; Prkaa1-fl/fl mice) significantly attenuated renal fibrosis following IRI. Single-cell RNA sequencing analysis further revealed that AMPKα1 deletion reduced the accumulation of Arg1+ MMP12+ macrophages and diminished a profibrotic tubular epithelial cell (TEC) subpopulation marked by persistent expression of PDGFB and VCAM1. These macrophages were shown to interact with PDGFB+ VCAM1+ TECs. Mechanistically, macrophage-derived TWEAK signaling through its receptor Fn14 promoted PDGFB production in TECs, driving maladaptive changes and a fibrogenic phenotype. Importantly, TWEAK neutralization effectively mitigated the AKI-to-CKD transition. Together, our results identify macrophage AMPK as a key redox sensor that, upon activation by oxidative stress, initiates maladaptive macrophage-TEC crosstalk, ultimately promoting renal fibrosis and CKD progression.

BACKGROUND:Diabetic kidney disease (DKD) is a major microvascular complication of diabetes, with microcirculatory dysfunction and immune injury as its core pathological features. Extracellular vesicles (EVs) act as key mediators of intercellular communication, but it remains unclear whether EV-encapsulated microRNAs (miRNAs) are involved in the crosstalk between endothelial cells (ECs) and monocytes in DKD. METHODS:EVs were isolated from monocytes and ECs under normal-glucose and high-glucose conditions. After characterization of EVs, differentially expressed miRNAs were screened. RNase/Triton functional assays, dual-luciferase reporter assays, gain- and loss-of-function experiments, and rescue experiments were further performed to validate the regulatory mechanisms associated with EV-miRNAs in vivo and in vitro. RESULTS:Under high-glucose conditions, monocyte-derived EVs aggravated EC injury by upregulating miR-191-3p, which targets CYLD and thereby activates the NF-κB pathway. Meanwhile, EC-derived EVs enhanced monocyte inflammation and adhesion by downregulating miR-615-3p, upregulating IFNGR2, and activating the STAT3 pathway. Targeted intervention of these key molecules effectively ameliorated cellular injury in vitro and partially relieved renal damage in vivo. CONCLUSIONS:This study confirms that EV-miRNA-mediated EC-monocyte crosstalk is involved in the pathogenesis of DKD, and establishes two core regulatory axes: miR-191-3p/CYLD/NF-κB and miR-615-3p/IFNGR2/STAT3. It also reveals an intrinsic link between microcirculatory dysfunction and immune injury in DKD, while the potential of these miRNAs as diagnostic biomarkers and therapeutic targets still remains to be further validated.

Background Diabetic kidney disease (DKD) is a common condition with few treatment options, and inflammation plays a pivotal role in its progression. Luteolin, a natural compound found in traditional Chinese herbs, is known for its anti-inflammatory properties, making it a potential treatment for DKD. But its effect and mechanisms in DKD remain incompletely elucidated. Methods Renoprotective effects of luteolin in db/db mice were assessed with BUN, Scr, uACR, and PAS staining. Flow cytometry and extraction of total membrane proteins were conducted to examine the abundance of full-length TREM2 on the membrane of macrophages. Co-culture of differentially treated macrophages and HK2 cells evaluated luteolin’s impact on efferocytosis. The molecular target of luteolin was elucidated through virtual molecular analysis, SPR, and ADAM10 activity assays. Results Luteolin reduced uACR, BUN, and SCr levels. Histologic analyses showed decreases in mesangial matrix, glomerular volume, GBM thickness, and foot process effacement. Tubular injury scores and KIM1 expression were lowered, while megalin and cubilin expression increased. Renal macrophage infiltration, iNOS+ cells, and IL-1β, IL-18, TNF-α, and MCP-1 levels were reduced. Luteolin elevated TREM2+ macrophages with decreased sTREM2 in vivo and in vitro. Immunofluorescence confirmed increased TREM2+ macrophages and enhanced full-length TREM2 on cell membrane. Luteolin exhibited dose-dependent binding to ADAM10 and inhibited its activity without affecting ADAM10 expression. In co-culture system, luteolin increased p-DAP12, p-SYK, and PHrodo+ cell counts. Apoptotic cells in kidney tissue decreased, while Rab5a and Rab7a expression were upregulated. Conclusions Luteolin attenuates immunoinflammation and pathological injury in db/db mice by enhancing the efferocytosis of apoptotic renal tubular cells by TREM2+ macrophages. The potential mechanism of luteolin involves binding to ADAM10 and inhibiting its activity, which attenuates aberrant shedding of full-length TREM2 from macrophages and potentiates downstream TREM2 signaling. Collectively, luteolin provides a promising option for ameliorating immune inflammation in DKD, demonstrating strong translational potential.

Lupus nephritis (LN) treatment remains challenging because of the limited efficacy and substantial side effects of conventional immunosuppressive therapies. Traditional Chinese medicine (TCM), with its holistic and multitarget approach, offers unique therapeutic potential. The emerging gut–kidney axis theory provides a new framework for understanding LN pathogenesis by linking gut dysbiosis and intestinal barrier injury to renal inflammation. This review systematically examines the role of gut–kidney axis dysregulation in LN progression and establishes connections between the TCM spleen–kidney correlation theory and this modern concept. Accumulating evidence suggests that TCM compounds and active ingredients alleviate renal injury and improve LN through multiple mechanisms. TCM compounds modulate the gut microbiota composition, enhance intestinal barrier integrity, reduce endotoxin translocation, and suppress systemic inflammation. These findings position the gut–kidney axis as a critical target for TCM intervention. Through multicomponent synergy, TCM restores gut homeostasis and inhibits aberrant immune responses. Future studies should integrate multiomics approaches, including metagenomics and metabolomics, and prospective clinical trials should dynamically track the gut microbiota and metabolite profiles in LN patients. Such investigations will clarify the precise mechanisms by which TCM modulates the gut–kidney axis and facilitate the development of personalized TCM-based therapeutic strategies.

Hyperuricemia is characterized by elevated serum uric acid levels and is associated with multiple diseases. Studies have consistently demonstrated that the prevalence of hyperuricemia in high-altitude areas is significantly higher than that in low-altitude areas. For high-altitude hyperuricemia, some environmental and genetic factors exhibit distinct characteristics among patients. Hyperuricemia also contributes to the onset and progression of a range of high-altitude-related disorders. Although studies have identified the characteristics of high-altitude hyperuricemia, the associations between elevated uric acid levels and influencing factors remain to be fully elucidated. This perspective compiles data from global epidemiological studies and clinical practices, and provides an exploration of the factors contributing to elevated uric acid levels at high altitudes. Additionally, we uncover the metabolic processes in patients with hyperuricemia and the correlation between hyperuricemia and high-altitude-related diseases, providing a foundation for developing more targeted therapeutic approaches and advanced pharmaceutical strategies.

The liver and kidneys are often synchronously affected by various diseases, posing significant health challenges. Simultaneously monitoring their damage would benefit rational drug use. Herein, a new probe, SQE-715-CD, was developed to concurrently assess liver and kidney injuries using in vivo NIR-II fluorescence imaging. In addition to diagnostic advancements, this research delves into the therapeutic potential of flavonoids in protecting against liver and kidney damage caused by cisplatin. Among the seven flavonoids tested, Apigenin stands out for its substantial reduction in cisplatin-induced toxicity in both organs. Further experiments reveal that Apigenin's pretreatment lowers kidney inflammation and inhibits the activation of crucial signaling molecules p38, ERK, and JNK. These results suggest a possible mechanism behind Apigenin's protective effects and underscore its significance in reducing nephrotoxicity. The capability for in vivo simultaneous monitoring of liver and kidney functions proposed in this study could provide another therapeutic drug evaluation and screening method.

QuestionWhat is the effect of finerenone in patients with chronic kidney disease due to glomerular diseases?FindingsIn this prespecified exploratory analysis of a randomized clinical trial that enrolled 903 participants with glomerular diseases, finerenone, compared with placebo, slowed kidney function decline (difference in eGFR slope decline, 073 mL/min/1.73 m2 per year), reduced albuminuria, and lowered the risk of kidney failure or sustained loss of kidney function, with consistent effects across glomerular disease subtypes.MeaningFinerenone may have an important role in preserving kidney function in patients with glomerular diseases. ImportanceGlomerular diseases are a leading cause of chronic kidney disease (CKD) and kidney failure. Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, reduces the risk of kidney function loss in CKD, but its effects in individuals with CKD due to glomerular diseases are uncertain.ObjectivesTo evaluate the efficacy and safety of finerenone in patients with glomerular diseases.Design, Setting, and ParticipantsPrespecified exploratory subgroup analysis of a phase 3, randomized, double-blind, placebo-controlled trial conducted across 24 countries and regions, focusing on participants with an investigator-reported glomerular disease diagnosis. The overall trial enrolled adults with nondiabetic CKD and an estimated glomerular filtration rate (eGFR) of either (1) at least 25 to less than 60 mL/min/1.73 m2 and urinary albumin to creatinine ratio of at least 200 mg/g to less than 500 mg/g or (2) an eGFR of at least 25 to less than 90 mL/min/1.73 m2 and urinary albumin to creatinine ratio of at least 500 mg/g to less than 3500 mg/g.InterventionFinerenone 10 mg or 20 mg taken orally once daily (n = 446) vs matching placebo (n = 457).Main Outcomes and MeasuresAnnualized rate of eGFR decline (total eGFR slope) from baseline to month 32 (primary outcome of the main trial); percent change in albuminuria to 12 months; and a composite outcome of kidney failure or sustained 40% or more decline in eGFR (prespecified exploratory outcomes).ResultsOf 1584 participants, 903 (57.0%) had investigator-reported glomerular disease, including 416 (46.1%) with immunoglobulin A nephropathy, 215 (23.8%) with focal segmental glomerulosclerosis, and 90 (10.0%) with membranous nephropathy. Participants with glomerular disease (mean [SD] age, 51.1 [13.6] years; 362 female [40.1%]; 558 Asian [61.9%]) had a mean eGFR of 48.8 mL/min/1.73 m2 and median urinary albumin to creatinine ratio of 839.6 mg/g. The total eGFR slope up to 32 months was -3.50 mL/min/1.73 m2 per year with finerenone and -4.23 mL/min/1.73 m2 per year with placebo (0.73 mL/min/1.73 m2 per year difference; 95% CI, 0.22-1.24). Finerenone reduced albuminuria at month 12 by 42% (95% CI, 35%-48%) and lowered the risk of kidney failure or 40% or more eGFR decline (7.42 vs 9.60 events per 100 patient-years; hazard ratio, 0.74; 95% CI, 0.57-0.97).Conclusions and RelevanceIn this exploratory analysis, treatment with finerenone slowed kidney function decline, reduced albuminuria, and lowered the risk of kidney failure or substantial loss of kidney function in patients with glomerular diseases. These findings suggest an important role for finerenone in preserving kidney function in this population.Trial RegistrationClinicalTrials.gov Identifier: NCT05047263 This exploratory analysis of a randomized clinical trial evaluates the efficacy and safety of finerenone in reducing chronic kidney disease of participants with glomerular diseases, including disease subtype.

OBJECTIVE:To clarify the distribution of Traditional Chinese Medicine (TCM) symptoms, syndrome elements and complications in chronic kidney disease stage 5 (CKD5) patients with type 2 diabetes mellitus (T2DM), and to analyze the correlation factors between dialysis and non-dialysis patients, so as to provide reference for clinical syndrome differentiation and treatment. METHODS:The general information, laboratory indicators, and TCM syndrome factors of CKD5 patients with T2DM were obtained upon admission. The participants were divided into non-dialysis and dialysis groups according to the treatment methods used. Multivariate logistic regression was used for analysis. The probability of planned dialysis in CKD5 patients with T2DM was calculated by combining multiple TCM syndrome factors, and a receiver operating characteristic curve was drawn. RESULTS:Approximately 77.2% of the study participants were men, with a median age of 59 years. A total of 277 and 95 patients comprised the non-dialysis and dialysis groups, respectively. The median duration of dialysis was 49.6 d. The dialysis group had a significantly higher serum creatinine level; a significantly lower estimated glomerular filtration rate, serum uric acid level, and 24-h urinary protein level; and a significantly lower proportion of patients with atherosclerosis (P < 0.01). The frequencies of Water stagnation pattern, Damp retention pattern, Heart deficiency pattern, and Lung deficiency pattern in the dialysis group were significantly higher (P < 0.01，P < 0.05), while the frequencies of Phlegm turbidity pattern and Kidney deficiency pattern were significantly lower (P < 0.01). Male sex [odds ratio (OR) = 1.780], Heart deficiency pattern (OR = 3.714), Yindeficiency pattern (OR = 2.262), and Water stagnation pattern (OR = 1.984) were factors related to planned dialysis in CKD5 patients with T2DM. The area under the receiver operating characteristic curve for planned dialysis in CKD5 patients with T2DM was 73.8% [95% confidence interval (0.680, 0.797), P < 0.001]. CONCLUSIONS:Male sex, Heart deficiency pattern, Yindeficiency pattern, and Water stagnation pattern were correlated with planned dialysis in CKD5 patients with T2DM. Kidney deficiency pattern and Phlegm turbidity pattern were correlated with CKD5 patients with T2DM who had not yet started planned dialysis. The study of TCM syndrome elements provides therapeutic ideas for relieving the uncomfortable symptoms of CKD 5 patients with T2DM, and provides reference for clinical syndrome differentiation and treatment.

Background:Severe acute kidney injury (AKI) is associated with high mortality. Current blood purification technologies fail to replace the biological functions of renal tubular epithelial cells (RTECs), such as active transport, acid-base homeostasis, and endocrine regulation. The integration of viable RTECs into an extracorporeal circuit to construct a bioartificial kidney represents a potential strategy for renal functional support. However, its translation is constrained by the rapid loss of seed cell phenotypes, immune and coagulation activation triggered by conventional materials, and a lack of in vivo validation in large animal models. However, three key challenges hinder its clinical translation, which this study seeks to address: the rapid loss of seed cell phenotypes, immune and coagulation activation triggered by conventional materials, and a lack of in vivo validation in large animal models. Methods:We engineered a renal tubule assist device (RAD) that integrates viable cells with a functionalized interface. First, we established an immortalized human proximal tubule cell line [immortalized renal tubular epithelial cell line (iRTEC)] and achieved scalable expansion using a microcarrier system. Second, we fabricated a cell-supporting interface [chlorogenic acid/poly-L-lysine-modified pristine nanofibrous membrane (CA/PLL-PNF)] with antioxidant properties and enhanced hemocompatibility via the layer-by-layer self-assembly of PLL and CA onto polyacrylonitrile nanofibrous membranes. Finally, we assembled these components into a flat-plate bioreactor and evaluated its extracorporeal performance in a Bama miniature pig model after bilateral nephrectomy. Results:iRTECs were stably expanded on microcarriers while maintaining a proximal tubule phenotype, and these cells outperformed existing cell lines in terms of amino acid hydrolysis and transmembrane transport, acid-base regulation, water transport, and endocrine responsiveness. With respect to the supporting interface, CA/PLL-PNF effectively scavenged diverse free radicals and mitigated cellular oxidative stress. Proteomic analysis confirmed that this modification remodeled the plasma protein corona, which significantly reduced the adsorption of complement and coagulation factors. In the bilaterally nephrectomized pig model, the RAD safely maintained extracorporeal circulation for 4 h-the duration of routine clinical dialysis-and preserved internal homeostasis. The antioxidant interface significantly attenuated circulating lipid peroxidation during treatment. Compared with hemofiltration alone, the RAD significantly enhanced the clearance of middle-molecule toxins (β2-microglobulin) and reduced proinflammatory cytokine levels at the outlet, demonstrating its capacity for the active modulation of local inflammation. Conclusions:This study established a renal support platform that integrates viable cells and functional materials. The device exhibited multidimensional biological efficacy in toxin clearance and internal homeostasis regulation and achieved stable extracorporeal circulation in a preclinical large animal model, which provides experimental evidence for advanced organ support strategies in the setting of severe AKI.

BACKGROUND:Renal fibrosis is a common pathological feature of chronic kidney disease (CKD) but its underlying mechanisms remain incompletely understood. Our previous study demonstrated that insulin-like growth factor-binding protein 5 (IGFBP-5) promotes glycolytic reprogramming in vascular endothelial cells (ECs) and exacerbates renal inflammation in diabetic kidney disease. METHODS:Human renal proximal tubular epithelial cells (HK-2) and human umbilical vein endothelial cells (HUVECs) were used. A co-culture system was employed to investigate endothelial cell-tubular epithelial cell (EC-TEC) crosstalk. Unilateral ureteral obstruction (UUO) and aristolochic acid nephropathy (ANN) models were established in wild-type (WT), global IGFBP-5-/- and endothelial-specific Tie-2 Cre;IGFBP-5-/- mice. Expression levels of IGFBP-5, TGF-β1 and fibrosis markers were assessed to investigate the role of IGFBP-5 in renal fibrogenesis. RESULTS:Serum IGFBP-5 levels were significantly elevated in patients with CKD. Genetic ablation of IGFBP-5 attenuated renal fibrosis in murine models, demonstrating its critical role in fibrogenesis. IGFBP-5 was predominantly expressed in ECs and endothelial-specific deletion delayed renal fibrosis progression via suppression of the TGF-β1/Smad3 pathway. In vitro, endothelial-derived IGFBP-5 promoted a profibrotic phenotypic transformation in TECs through AKT-mediated phosphorylation of the TGF-β1/Smad3 axis. Conversely, TGF-β1 stimulated IGFBP-5 biosynthesis and secretion in ECs via the ERK signalling pathway, establishing a self-amplifying feedback loop. This reciprocal IGFBP-5/TGF-β1 crosstalk between ECs and TECs was confirmed in co-culture experiments. CONCLUSION:Our findings reveal a novel EC-TEC crosstalk axis mediated by reciprocal IGFBP-5/TGF-β1 signalling, which is a critical driver of renal fibrosis. IGFBP-5 emerges as a promising therapeutic target for inhibiting renal fibrogenesis in CKD.

Background:The uric acid-to-albumin ratio (UAR) has emerged as a potential composite biomarker reflecting oxidative stress and nutritional status, both of which are relevant to aging and mortality risk. However, its prognostic value in extremely long-lived individuals remains unclear. Methods:A prospective cohort study involving 1,002 centenarians from China Hainan was conducted between June 2014 and December 2016. Participants were followed for survival status through March 31, 2023. Restricted cubic spline (RCS) modeling, Cox proportional hazards regression, and Kaplan-Meier survival analyses were employed to assess the association between UAR and mortality risk. Results:After excluding 78 centenarians, the cohort included 924 centenarians (median age: 102 years; 18.29% male). During a median follow-up of 29.70 months, 854 (92.42%) died. RCS analysis indicated a statistically significant overall association between UAR and mortality (adjusted P for overall = 0.009), with evidence of non-linearity (adjusted P for non-linearity = 0.029). In multivariable Cox regression analysis, individuals in the higher UAR quartile (Q4) demonstrated a 28.7% increased risk of mortality compared with those in the lower three quartiles (Q1-Q3) (adjusted hazard ratio: 1.287, 95% CI: 1.093,1.516; P = 0.003). Kaplan-Meier analysis further revealed that participants in Q4 had a significantly shorter median survival time (26 months) compared with those in Q1-Q3 (32 months) (log-rank test, P < 0.001). Conclusion:Elevated UAR is independently associated with increased all-cause mortality in centenarians, suggesting its potential utility as a prognostic biomarker for risk stratification in exceptionally long-lived populations.

BackgroundWith advancing age, multiple systems, including the muscular and respiratory systems, undergo degenerative changes. While the relationship between sarcopenia and lung function is well-established in patients with respiratory diseases, evidence remains limited in the general population. Therefore, this study aimed to investigate the relationship between sarcopenia indicators and lung function in a community-dwelling population.MethodsBasic information, laboratory biochemical parameters, handgrip strength (HGS), gait speed (GS), five times sit-to-stand test (5STS) time, skeletal muscle mass index (SMI) and lung function parameters, were collected from a community-dwelling population in Beijing, China. Linear regression analysis was employed to investigate the relationship between sarcopenia indicators and lung function parameters, and logistic regression analysis was utilized to examine their association with lung function statuses.ResultsA total of 2,526 community volunteers were enrolled and divided into three groups based on lung function: normal spirometry (n = 2,032), preserved ratio impaired spirometry (PRISm) (n = 231), and obstructive spirometry (n = 273). After adjusting for covariates, linear regression analysis revealed that HGS, GS, and SMI were positively correlated with forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), while 5STS was negatively correlated with FEV1 and FEV1/FVC ratio. Logistic regression analysis revealed that lower HGS and longer 5STS time were associated with a higher risk of PRISm, while slower GS, longer 5STS time were associated with an increased risk of obstructive spirometry. Sarcopenia was associated with both PRISm risk and obstructive spirometry risk.ConclusionThis study demonstrates that sarcopenia indicators are closely associated with lung function in community-dwelling individuals. As a condition that significantly impacts healthy aging and is linked to both quality of life and longevity, enhancing the early identification and management of sarcopenia within community settings may yield multi-organ benefits.