Search Results (1,293)

Background/Objectives: Patients with ST-segment elevation myocardial infarction (STEMI) may develop gastrointestinal (GI) bleeding. We aimed to assess the impact of GI bleeding on in-hospital outcomes in patients with STEMI. Methods: This retrospective study was performed using the National Inpatient Sample from the United States of America from the years 2016–2021 to identify STEMI hospitalizations. Index admissions were stratified according to concomitant GI bleeding. The primary outcome was in-hospital mortality; secondary outcomes were inflation-adjusted total charges, total costs, length of stay ≥7 days, acute kidney injury, and cardiogenic shock. Multivariable analysis with a logistic regression model was used to identify associations with in-hospital mortality and several secondary outcomes. Results: Of 1,013,800 index admissions with STEMI, 22,260 (2.2%) had concomitant GI bleeding. Patients with GI bleeding were older and more frequently had comorbidities such as chronic heart failure, liver disease, and chronic kidney disease. In-hospital mortality was higher in patients with GI bleeding (27.8% versus 7.6%, p < 0.001). GI bleeding was associated with 2.30 times (2.11–2.51, p < 0.001), 3.78 times (3.50–4.07, p < 0.001), 2.99 times (2.76–3.24, p < 0.001), and 2.62 times (2.42–2.83, p < 0.001) increased odds of in-hospital mortality, length of stay ≥7 days, acute kidney injury, and cardiogenic shock, respectively. However, liver disease was most strongly positively associated with in-hospital mortality (odds ratio [OR]: 5.50 [5.21–5.80], p < 0.001), acute kidney injury (OR: 6.50 [6.18–6.84], p < 0.001), and cardiogenic shock (OR: 5.47 [5.22–5.74], p < 0.001). Conclusions: GI bleeding was associated with in-hospital mortality, adverse outcomes, and increased resource utilization in patients with STEMI, highlighting the need for risk stratification, implementation of preventative strategies, and timely treatment of GI bleeding. Full article

Traditionally, chronic wounds including diabetic foot ulcers (DFUs), pressure ulcers (PUs), venous leg ulcers (VLUs), arterial ulcers, inflammatory and autoimmune-associated ulcers, infected chronic wounds, and non-healing post-surgical wounds are treated as localized diseases of skin and soft tissue damage. However, these lesions are increasingly acknowledged as chronic inflammatory states with consequences extending beyond the wound bed and often arising in the setting of systemic dysfunction. Across wound types, shared features include persistent inflammation, oxidative stress, endothelial dysfunction, immune imbalance, protease dysregulation, infection or biofilm burden, metabolic disturbance, and impaired regenerative signaling. These abnormalities may promote systemic cytokine release, vascular dysfunction, neurohumoral activation, oxidative injury, and maladaptive remodeling. Cardiac dysfunction is already known to impair wound healing. In contrast, whether chronic non-healing wounds are associated with or may contribute to cardiac damage resulting in heart failure remains insufficiently defined. Emerging epidemiologic and mechanistic evidence suggests that chronic non-healing wounds may amplify cardiovascular stress, particularly in vulnerable patients with diabetes, obesity, frailty, kidney disease, or pre-existing vascular disease. This narrative review explores the conceptual hypothesis that chronic non-healing wounds may contribute to systemic cardiovascular stress and cardiac dysfunction. It integrates clinical and mechanistic opportunities, outlines potential pathways, including extracellular vesicle (EV) signaling, and highlights key knowledge gaps and therapeutic implications in the wound–heart axis. Full article

Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite of dietary choline and L-carnitine, has emerged as a leading molecular mediator of the gut–heart–kidney axis in heart failure (HF). This state-of-the-art narrative review synthesizes evidence from 14 observational studies (13 prospective cohorts and one cross-sectional analysis), encompassing a heterogeneous range of HF settings, including established chronic HF, acute decompensated HF, incident HF in community cohorts, and subclinical myocardial injury. Across these populations, elevated circulating TMAO has been associated with adverse outcomes, including mortality, rehospitalization, and major adverse cardiovascular events, although the strength and consistency of associations vary by HF phenotype, renal function status, and population ancestry. The prognostic independence of TMAO is attenuated after adjusting for renal function in several cohorts, reflecting both obligatory renal clearance and a potentially bidirectional relationship with kidney injury. TMAO was not reduced during neurohormonal GDMT uptitration in the BIOSTAT-CHF study, suggesting that gut microbiota dysbiosis may represent a pathophysiological axis not reached by current HF treatment. The field has evolved through three thematic stages: TMAO as a single prognostic biomarker, TMAO within cardiorenal pathophysiology, and multimetabolite and multipathway risk profiling. Beyond the TMAO pathway, emerging evidence for phenylacetylglutamine (PAGln), short-chain fatty acids (SCFAs), and protein-bound uremic toxins as parallel gut-derived cardiovascular mediators supports a multidimensional metabolite profiling approach. Several cohorts suggest that selected multimetabolite panels may provide additional prognostic information beyond TMAO alone, although their composition, calibration, and external validity remain uncertain. Population-specific variation in TMAO levels and prognostic thresholds complicates universal clinical application. Without human interventional data demonstrating that lowering TMAO improves cardiovascular outcomes, TMAO remains a prognostic risk marker rather than a validated clinical target. Clinical translation requires resolving the renal confounding problem, validating multimetabolite panels across diverse populations, and conducting intervention trials targeting the gut–heart–kidney axis. Full article

Background: Valvular heart disease frequently accompanies acute heart failure (AHF), yet most studies address single valve lesions, and the prognostic weight of concurrent multivalvular involvement is less well defined. We examined the prevalence of single- and multi-valve disease and its relationship with one-year mortality. Methods: We analyzed 530 consecutive patients enrolled in a prospective single-center AHF registry between February 2023 and June 2025 and followed for 12 months. Aortic, mitral and tricuspid disease was graded according to European Society of Cardiology/European Association of Cardiovascular Imaging (ESC/EACVI) criteria, a valve being considered involved when it carried at least moderate stenosis and/or regurgitation; multivalvular disease was defined as involvement of two or more valves. The primary endpoint was one-year all-cause mortality. Cox regression was adjusted for admission log N-terminal pro-B-type natriuretic peptide (NT-proBNP), frailty (Clinical Frailty Scale ≥ 5) and age. In-hospital acute kidney injury was examined descriptively but was not entered into the models, because it is ascertained after admission. Results: Overall, 71.3% of patients had at least one significantly diseased valve—mitral in 44.3%, tricuspid in 43.8% and aortic in 27.5%—and 34.9% had multivalvular involvement. One-year mortality rose stepwise with the number of valves involved: 19.7%, 24.9%, 36.3% and 54.0% for zero, one, two and three valves, respectively (log-rank p < 0.001), corresponding to a crude hazard ratio (HR) of 1.51 (95% confidence interval [CI] 1.28–1.78) per additional valve. Multivalvular versus single or no valve involvement carried a crude HR of 2.07 (1.51–2.84) and remained associated with mortality after adjustment (HR 1.48, 95% CI 1.06–2.07, p = 0.020), as did each additional valve (HR 1.22, 1.03–1.45, p = 0.023). Adjustment for clinically manifest right heart failure (HF) attenuated the association with mortality (HR 1.15, 95% CI 0.96–1.37), whereas the association with the triple composite remained significant (HR 1.19, 95% CI 1.03–1.36). Propensity-score adjustment excluding right HF retained the association with mortality (HR 1.43, 95% CI 1.02–2.00), whereas inclusion of right HF attenuated it (HR 1.33, 0.94–1.87). The association was not detectable in the 304 patients without clinically manifest right HF (HR 1.06, 0.80–1.41, p = 0.69). In a post-discharge sensitivity analysis, the adjusted associations were directionally similar but did not reach statistical significance. Conclusions: In hospitalized AHF, multivalvular involvement was common, followed a predominantly mitral–tricuspid pattern, and identified an older, frailer, more congested phenotype with substantial right-sided and chronic renal involvement. Valve burden showed a graded association with one-year mortality that persisted after adjustment for baseline prognostic characteristics, but was attenuated once right-sided involvement was taken into account, whether by direct adjustment or by propensity methods; the association was retained when right HF was omitted from the propensity model. Because right-sided variables lie downstream of significant tricuspid disease, this attenuation is what adjustment for an intermediate is expected to produce and does not establish absence of prognostic value. Cumulative valve burden is therefore best interpreted as a powerful phenotypic marker of a more advanced HF phenotype with prominent right-heart involvement, rather than as an independent causal determinant of mortality. Full article

Objectives: This study aimed to identify ferro-aging-related hub genes in chronic kidney disease (CKD) and elucidate their potential roles in proximal tubular (PT) cells. Methods: Differential expression analysis was performed using GSE104954, and the differentially expressed genes were intersected with a set of ferro-aging-related genes. Feature selection was conducted using the least absolute shrinkage and selection operator (LASSO), support vector machine–recursive feature elimination (SVM-RFE), and random-forest algorithms. The findings were externally validated in GSE180394. Single-cell transcriptomic data from GSE183276 were then used to define the cellular localization and expression profile of the hub genes, and their regulatory networks were investigated using scTenifoldKnk-based in silico knockout and gene set enrichment analysis (GSEA). Results: Fourteen candidate genes were identified, of which IRF7 and SOCS2 were consistently selected by all three machine-learning algorithms. SOCS2 was significantly downregulated in both the discovery and validation cohorts and showed strong tissue-level discriminatory performance in the discovery cohort, with more modest performance in the external cohort. Single-cell analysis showed that SOCS2 downregulation occurred predominantly in PT cells; CKD PT cells also exhibited increased ACSL4 expression and the enrichment of the ferroptosis pathway. In silico SOCS2 knockout further identified 77 significantly perturbed genes, primarily associated with mitochondrial oxidative phosphorylation, oxidative stress, and metabolic homeostasis. Conclusions: Collectively, these findings identify SOCS2 as a candidate gene associated with a ferro-aging-related transcriptomic signature in CKD PT cells. The observed changes in ACSL4, ferroptosis-related pathways, mitochondrial oxidative phosphorylation, and oxidative stress networks are compatible with, but do not establish, a ferro-aging phenotype. Further functional validation is required to determine whether SOCS2 contributes causally to iron–lipid dysregulation and tubular injury in CKD. Full article

Chronic kidney disease (CKD) is characterized by progressive renal dysfunction and endothelial injury. Thrombomodulin (TM), encoded by the THBD gene, is released into the circulation as soluble TM (sTM) following endothelial damage; however, its clinical significance in CKD remains unclear. To address this question, public bulk and single-cell transcriptomic datasets were analyzed to characterize THBD expression and cellular localization in kidney injury, and a retrospective cohort of 278 hospitalized patients was used to evaluate circulating sTM levels across CKD stages and their associations with renal function, coagulation, and cardiac biomarkers. The transcriptomic analyses showed that THBD was upregulated in injured kidneys, positively correlated with a fibrosis-related transcriptional signature, and predominantly expressed in renal endothelial cells. Consistent with these findings, circulating sTM was elevated as early as stage 1 CKD and increased progressively with advancing disease stage. Higher sTM levels were positively associated with serum creatinine, serum urea, and urinary albumin-to-creatinine ratio (UACR), and inversely associated with estimated glomerular filtration rate (eGFR). In addition, sTM showed weak-to-modest associations with coagulation, fibrinolytic, and cardiac biomarkers. Multivariable analysis showed that eGFR remained independently associated with log-transformed sTM after adjustment for major clinical covariates (β = −0.0116, 95% CI −0.0141 to −0.0090, p < 0.001). ROC analysis showed that sTM discriminated CKD from non-CKD (AUC = 0.971) and early-stage CKD from non-CKD (AUC = 0.854), outperforming eGFR (AUC 0.920 and 0.565, respectively) and performing comparably to UACR. Collectively, these findings support sTM as a candidate biomarker associated with CKD severity whose interpretation should integrate endothelial injury and reduced renal elimination and prospective validation is warranted. Full article

Acute kidney injury (AKI) is a common critical syndrome with high morbidity and mortality, and a subset of patients may progress to chronic kidney disease. Recent studies have revealed that gut microbiota and their metabolites play pivotal roles in the pathogenesis of AKI. Under AKI conditions, the gut microbiota composition undergoes significant alterations, characterized by decreased beneficial bacteria and expansion of opportunistic pathogens, accompanied by impaired intestinal barrier and disordered microbial metabolism. Gut microbiota metabolites can be classified into protective metabolites (short-chain fatty acids, secondary bile acids, tryptophan metabolites, D-amino acids, and polyamines) and toxic metabolites (indoxyl sulfate, p-cresyl sulfate, trimethylamine N-oxide, and endotoxin). The former exert renoprotective effects through anti-inflammatory, antioxidant, and barrier-maintaining mechanisms, while the latter aggravate kidney injury via oxidative stress, inflammation activation, and hemodynamic disturbance. Based on the gut–kidney axis theory, interventions targeting gut microbiota (probiotics, prebiotics, fecal microbiota transplantation) and those targeting metabolites (supplementation of protective metabolites, removal of toxic metabolites) have shown promising prospects. This narrative review summarizes the characteristics of gut microbiota changes, classification and function of key metabolites, core mechanisms driving AKI, and microbiota-based intervention strategies, aiming to provide novel insights for early recognition and precision prevention of AKI. Full article

Contrast-associated acute kidney injury (CA-AKI) is an important complication of renal angiography in patients with atherosclerotic renal artery stenosis (RAS). We investigated the associations of the triglyceride–glucose (TyG) index, atherogenic coefficient (AC) and lipoprotein combined index (LCI) with CA-AKI in this population. This retrospective single-center study included 147 consecutive patients with atherosclerotic RAS undergoing renal angiography with or without renal artery intervention. CA-AKI was defined using a creatinine-based definition based on serum creatinine changes within 48–72 h after contrast exposure. Continuous variables were retained in their continuous form in the primary logistic regression analyses, and separate multivariable models were constructed for the TyG index, AC, and LCI, each adjusted for chronic kidney disease (CKD), left ventricular ejection fraction (LVEF), and contrast volume. Firth penalized logistic regression was performed as a sensitivity analysis. CA-AKI occurred in 22 patients (15.0%). In the adjusted model, a higher TyG index was associated with increased odds of CA-AKI (OR 4.263 per 1-unit increase, 95% CI 1.120–16.228; p = 0.034), whereas AC (OR 1.581, 95% CI 0.891–2.807; p = 0.118) and LCI (OR 1.047 per 10,000-unit increase, 95% CI 0.966–1.136; p = 0.264) were not significantly associated with CA-AKI. The association of the TyG index with CA-AKI remained significant in Firth penalized logistic regression (OR 3.48, 95% CI 1.17–14.33; p = 0.020). Higher contrast volume and lower LVEF were consistently associated with CA-AKI across the multivariable models. These findings suggest that the TyG index is associated with susceptibility to CA-AKI in patients with atherosclerotic RAS, although prospective validation is required before clinical application. Full article

Albuminuria is routinely used to assess kidney damage in diabetes, but it also conveys cardiovascular risk across the urinary albumin-to-creatinine ratio (UACR) distribution, including within A1. Whether sex modifies this relationship remains uncertain. This narrative review prioritizes longitudinal studies in type 2 diabetes mellitus (T2DM), analyses within A1 particularly, and distinguishes this direct evidence from the general population or chronic kidney disease cohorts, surrogate-endpoint studies, and experimental mechanisms. A few studies report formal sex-by-UACR interactions for selected outcomes, including mortality in broad kidney-disease populations and heart failure in diabetes. Many other apparent differences derive only from sex-stratified analyses and therefore do not establish effect modification. Differences in urinary creatinine excretion, body composition, hormonal exposure, kidney injury pathways, cardiovascular phenotype, and health-care ascertainment may alter the observed association, but most mechanistic evidence is indirect. Current evidence supports UACR as a continuous prognostic marker in both sexes but does not justify sex-specific diagnostic cut-offs, therapeutic thresholds, or response targets. UACR should be measured systematically, confirmed when abnormal or borderline, preferably repeated under standardized conditions, and interpreted with eGFR and the overall cardiovascular risk profile. Sex may provide additional clinical context; treatment should continue to follow guideline-based indications. Full article

MicroRNA-21 (miR-21) has long been regarded as one of the most promising molecular targets in chronic kidney disease (CKD) because of its consistent upregulation across diverse renal disorders and its involvement in fibrosis, inflammation, oxidative stress, and metabolic dysfunction. Strong preclinical evidence demonstrated that inhibition of miR-21 reduced kidney injury, preserved renal function, and improved survival in multiple experimental models, particularly Alport syndrome, leading to the clinical development of the antisense oligonucleotide lademirsen. However, despite a compelling biological rationale and encouraging animal data, the phase 2 HERA trial failed to demonstrate a clinically meaningful effect on the rate of kidney function decline, resulting in discontinuation of the program. This review examines the biological functions of miR-21 in CKD, summarizes the experimental and clinical evidence that supported its therapeutic development, and critically analyzes the factors that may explain the discrepancy between preclinical success and clinical failure. Particular attention is given to the distinction between disease-associated biomarkers and true therapeutic drivers, the limitations of animal models, disease heterogeneity, timing of intervention, and the complex regulatory networks underlying progressive kidney fibrosis. Rather than representing the end of miR-21 research, the experience with lademirsen provides valuable insights into the challenges of translating RNA-based therapies into clinical practice. Future therapeutic strategies will likely require earlier intervention, improved patient selection, robust biomarkers of target engagement, and combination approaches that address the multifactorial nature of CKD. The lessons learned from the lademirsen program may help guide the development of the next generation of RNA therapeutics for kidney disease. Full article

As a core organ responsible for metabolism and homeostatic regulation, the kidney performs physiological functions that encompass material excretion, fluid balance, electrolyte regulation, and endocrine control; and serves as a critical hub for maintaining the coordinated functioning of multiple organ systems. Kidney injury not only leads to disturbances in these core physiological functions but also generates systemic complications such as cardiovascular disease, hypertension, and diabetes mellitus through an “injury–inflammation–metabolic disorder” cascade. Epidemiologic studies and clinical statistics have revealed that acute kidney injury (AKI) may progress to chronic kidney disease (CKD) because of maladaptive repair, impaired regeneration, and other factors. During this process, macrophages—particularly certain functionally specialized macrophage subtypes—engage in complex intercellular communication with neighboring cells that include renal tubular epithelial cells, endothelial cells, fibroblasts, and platelets, thereby forming pathological signaling networks that collectively drive persistent inflammation and the progression of renal fibrosis. Macrophages thus play complex and dynamic dual regulatory roles throughout the initiation, progression, and repair of kidney injury, and their functional polarization and phenotypic transformation directly influence the pathological progression of kidney diseases. We herein aimed to elucidate the roles of AKI-to-CKD transition-associated macrophages, especially the subtypes with specialized functions in kidney diseases and to systematically review current research progress, thus to provide a reference for advancing basic research and clinical diagnostic and therapeutic strategies for kidney diseases. Full article

Chronic kidney disease (CKD) represents a major global health challenge, affecting more than 10% of the population and contributing substantially to morbidity and premature mortality. Growing evidence identifies oxidative stress and mitochondrial dysfunction as central drivers of renal injury and disease progression across diverse etiologies. The kidney is one of the most mitochondria-rich organs in the body, reflecting the high bioenergetic demands required for tubular reabsorption and metabolic homeostasis. Disruption of mitochondrial oxidative phosphorylation, excessive production of reactive oxygen species (ROS), and impaired mitochondrial quality control mechanisms promote tubular injury, inflammation, and fibrosis. In particular, dysfunction of the electron transport chain, activation of NADPH oxidase isoforms—especially NOX4—and alterations in mitochondrial dynamics create a vicious cycle of oxidative damage and bioenergetic failure. Emerging evidence highlights the importance of mitochondrial quality control pathways, including fusion–fission balance, PINK1/Parkin-mediated mitophagy, and mitochondrial biogenesis regulated by PGC-1α and TFAM. Additional mechanisms include ferroptosis, epigenetic regulation, mitochondrial DNA-mediated innate immune activation, and Na⁺/K⁺-ATPase-linked redox signaling. At the translational level, redox and mitochondrial biomarkers and targeted therapies are biologically compelling, but the evidence is uneven: most candidate biomarkers remain insufficiently standardized, and direct mitochondria-targeted interventions are supported predominantly by preclinical studies or small human proof-of-concept trials. This review therefore emphasizes not only mechanistic advances but also conflicting findings, model limitations, and the barriers that currently separate experimental efficacy from clinically meaningful CKD outcomes. Full article

Hypertension is a major attributed cause of chronic kidney disease (CKD) and kidney failure, yet the cellular mechanisms linking chronic hemodynamic and neurohormonal stress to progressive nephron loss remain incompletely defined. Interpretation is further complicated by the clinical heterogeneity and limited pathological validation of hypertensive nephrosclerosis. Autophagy and mitophagy are important intracellular quality-control pathways and have been increasingly implicated in hypertensive kidney injury. In this review, we critically appraise the available evidence using a multidimensional ACGEM framework that evaluates autophagy/mitophagy measurement (A), cell-type resolution (C), genetic manipulation (G), experimental causality (E), and disease-model relevance (M) as independent dimensions. The available literature does not support a uniform increase or decrease in autophagy during hypertensive kidney disease. Rather, autophagic responses appear to depend on renal cell type, hypertensive stimulus, disease stage, and the component of the pathway being measured. In podocytes, chronic angiotensin II exposure provides evidence of impaired autophagic flux with a protective role for intact autophagy, whereas mineralocorticoid stress can induce a compensatory increase in autophagic flux. Tubular studies likewise suggest protective roles for effective autophagic and mitochondrial quality control, although direct cell-specific causal evidence in hypertensive models remains limited. Across the field, most studies rely on static autophagy-associated markers and bulk kidney measurements, while dynamic flux assessment, cell-specific genetic approaches, and direct evaluation of lysosomal competence remain uncommon. Observations from APOL1-associated kidney disease, chronic interstitial nephritis in agricultural communities, proteinuric overload, aging, and obesity provide mechanistic or pathological precedent for lysosomal vulnerability but do not constitute direct evidence for classical hypertensive nephrosclerosis. We therefore propose, as a falsifiable working hypothesis rather than an established mechanism, that lysosomal clearance may become rate limiting in a subset of hypertensive CKD. Testing this model will require longitudinal, cell-type-resolved flux measurements, direct assessment of lysosomal function, and pathological validation in biopsy-confirmed human hypertensive nephrosclerosis. Full article

Although the prevalence of acute kidney injury and chronic kidney disease remains high and effective therapeutic targets remain scarce, significant progress has been made in recent years across the following major directions: G2/M phase cell cycle arrest, DNA damage, mitochondrial dysfunction, hypoxia-inducible factor signaling, dysregulated autophagy, and epigenetic alterations. RGC-32 is abundantly expressed in all tubular segments of normal renal tissues and is primarily localized to the cytoplasm and perinuclear region of renal tubular epithelial cells. Moreover, RGC-32 is involved in cell cycle regulation as well as cell proliferation and differentiation. To explore the functional role of RGC-32 in renal repair after acute ischemia–reperfusion injury, we utilized CRISPR-Cas9 technology combined with Cre/loxP recombination to generate a novel, renal tubule-specific RGC-32 knockout mouse model and systematically characterized its phenotype. Our findings demonstrate that renal tubule-specific RGC-32 deficiency does not impair normal growth or baseline renal function but alters the distribution of peripheral blood T lymphocyte subsets; whether this alteration contributes to renal immune regulation remains to be determined by future functional studies. More importantly, upon IRI, RGC-32 knockout in renal tubules leads to significantly aggravated renal dysfunction, elevated injury markers, and a possible association with enhanced chronic fibrosis. Full article

Plasma prorenin is commonly elevated in patients with diabetes and has been associated with the development of albuminuria and progression of diabetic nephropathy. Because albuminuria often reflects podocyte injury, the pathogenic role of prorenin in podocyte dysfunction warrants further investigation. In this study, we examined the association between prorenin and podocyte injury, as well as glomerular fibrosis, using a transgenic rat model in which prorenin is inducibly expressed and secreted from the liver. cyp1a1-prorenin transgenic rats were randomized to receive diets containing increasing concentrations of the gene activator indole-3-carbinol (I3C; 0.05%, 0.15%, or 0.3%) for 4 weeks. Wild-type rats maintained on a normal diet served as controls. I3C administration resulted in a dose-dependent increase in plasma prorenin levels in transgenic rats. Elevated prorenin was associated with increased mean arterial pressure and urinary albumin excretion, accompanied by a dose-dependent reduction in podocyte number and slit diaphragm protein expression, as well as segmental foot process effacement and podocyte hypertrophy. In addition, increased prorenin stimulated renal expression of profibrotic factors and promoted glomerular fibrosis. Treatment with either amlodipine or enalapril for 6 weeks prevented the development of hypertension and partially attenuated podocyte injury, albuminuria, and renal fibrosis, without fully reversing these changes. These protective effects were associated with suppression of NF-κB- and Nox2-mediated inflammatory and oxidative stress pathways. Collectively, these findings demonstrate that prorenin promotes podocyte injury and glomerular fibrosis through mechanisms that are partially dependent on hypertension and angiotensin II but also involve angiotensin II-independent pathways. Full article