Search Results (2,203)

The cardiovascular–kidney–metabolic (CKM) syndrome has emerged as an integrated framework linking obesity, type 2 diabetes, chronic kidney disease (CKD), and heart failure with preserved or mildly reduced ejection fraction through shared mechanisms including inflammation, oxidative stress, endothelial dysfunction, and fibrosis. Persistent mineralocorticoid receptor overactivation plays a central role in this continuum, contributing to progressive cardiac and renal injury despite optimized renin–angiotensin system blockade. Finerenone, a selective non-steroidal mineralocorticoid receptor antagonist, has therefore gained increasing attention as a targeted strategy to reduce residual cardiorenal risk. This narrative review summarizes the mechanistic rationale and clinical evidence supporting finerenone across the CKM spectrum. Experimental data indicate that finerenone attenuates inflammation, fibrosis, myocardial hypertrophy, and adverse remodeling, while proteomic and translational analyses suggest biological complementarity with sodium–glucose cotransporter 2 inhibitors. Clinically, pivotal randomized trials have demonstrated that finerenone reduces kidney disease progression and major cardiovascular events in patients with CKD and type 2 diabetes, while the FINEARTS-HF trial extended these benefits to patients with heart failure with mildly reduced or preserved ejection fraction by reducing worsening heart failure events. Additional subgroup, pooled, and meta-analytic data reinforce the consistency of these effects across a broad range of cardiorenal phenotypes. Taken together, current evidence positions finerenone as an important component of contemporary CKM management, particularly in patients with diabetic CKD and selected heart failure phenotypes. Its principal value lies in targeting residual inflammatory and fibrotic risk beyond conventional hemodynamic and metabolic control. Future progress will depend on earlier phenotype recognition, improved implementation and adherence, and wider adoption of pathway-oriented combination therapy across the cardiorenal continuum. Full article

Cardiometabolic disease is increasingly shaped by the overlap among obesity, type 2 diabetes, chronic kidney disease, heart failure, and atherosclerotic cardiovascular disease, underscoring the need for prevention strategies that extend beyond glucose-centered care. This narrative review critically examines the mechanistic rationale, clinical evidence, guideline evolution, and practical implementation of sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitors) and glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists) within the cardiorenal–metabolic continuum. A structured literature search was conducted in PubMed, Scopus, and Web of Science, focusing primarily on publications from January 2019 to March 2026, with selected landmark studies from earlier years included for context. Priority was given to randomized controlled trials, major cardiovascular and kidney outcome trials, meta-analyses, clinical practice guidelines, scientific statements, and expert consensus documents. The reviewed evidence indicates that SGLT-2 inhibitors show the most consistent benefits in reducing heart failure events, slowing chronic kidney disease progression, and lowering cardiorenal risk, whereas GLP-1 receptor agonists are more strongly associated with reductions in major adverse cardiovascular events, residual atherosclerotic risk, and body weight. Emerging data also support extension of this therapeutic paradigm beyond diabetes, particularly in obesity-associated cardiovascular risk. Contemporary care is increasingly moving toward phenotype-informed treatment selection, earlier organ-protective intervention, and multidisciplinary management, although cost, access, tolerability, and implementation barriers remain important limitations. SGLT-2 inhibitors and GLP-1 receptor agonists are therefore central to modern cardiovascular prevention across the cardiovascular–kidney–metabolic spectrum. In this context, the proposed Cardiometabolic 2.0 framework may serve as a clinically oriented model for integrating these therapies within contemporary organ-protective care. Full article

Glucagon-like Peptide 1 (GLP-1)-based medications have been extensively studied for the management of type 2 diabetes, obesity, chronic kidney disease, and atherosclerotic cardiovascular disease. More recently, their potential role in preventing and treating heart failure has gained increasing attention. Given the strong pathophysiological links among diabetes, obesity, and heart failure, GLP-1-based medications represent a promising therapeutic option to improve morbidity and mortality across these interconnected conditions. In this review, we summarise and discuss recent studies involving GLP-1-based medications that have reported on HF-related outcomes. There is increasing evidence that these medications have beneficial effects on HF outcomes in patients with heart failure with preserved ejection fraction and possibly in those with mildly reduced ejection fraction. The usefulness of GLP-1-based medications in reduced ejection fraction HF remains to be defined. Full article

Background: Emerging evidence highlights the importance of the MIF–sCD74 axis in health and disease, including its role in regulating cell death. While studies in routine cardiac surgery suggest perioperative relevance, its role in end-stage heart failure (ESFH) patients undergoing left ventricular assist device (LVAD) implantation remains unexplored. Moreover, although MIF and sCD74 induce necroptosis in neonatal cardiac myofibroblasts, the effects of MIF, its paralog D-DT, and sCD74 on adult cardiac myofibroblasts (CMFs) are unknown. Methods: Plasma concentrations of sCD74, MIF and D-DT were measured perioperatively in a small cohort of patients with ESHF undergoing LVAD implantation (n = 20). As a preclinical model of ESHF, primary adult CMFs were treated with recombinant MIF, D-DT and sCD74 to evaluate their effects on cellular viability and health. Results: In LVAD patients, sCD74 and D-DT levels were significantly increased 24 h postoperatively, whereas MIF levels were reduced compared to baseline. ROC curve analysis demonstrated a good discriminatory power of 24 h post-OP sCD74 (AUC = 0.83), sCD74/MIF ratio (AUC = 0.82), and D-DT levels (AUC = 0.88) for acute kidney injury, composite outcome, and right heart failure (RHF), respectively. In adult CMFs, MIF and sCD74 synergistically reduced viable cell counts (p = 0.0083), whereas D-DT reduced cell counts in an sCD74-independent manner (p = 0.0004). Yet, measures of metabolism, proliferation, apoptosis and necrosis along with inflammatory gene expression remained unchanged. Conclusions: Our findings indicate that the balance of MIF, D-DT, and sCD74 during LVAD implantation may be clinically relevant. In particular, an imbalance characterized by elevated sCD74 or D-DT and reduced MIF levels 24 h post-surgery was associated with unfavorable clinical outcomes. Yet, the current findings are exploratory and hypothesis-generating because of a small sample size. Thus, the prognostic value of plasma levels for postoperative complications after LVAD implantation, and the effects of MIF/D-DT/sCD74 imbalance on cardiac myofibroblasts, need to be validated in larger cohorts and in advanced human experimental models. Full article

People affected by diabetes mellitus (DM), chronic kidney disease (CKD), or heart failure are often prescribed sodium–glucose cotransporter-2 inhibitors (SGLT2is) as a method of treatment. These drugs favorably affect glucose metabolism, as patients taking them have lower serum glucose levels. Another promising positive impact is protection against microvascular damage, cardiovascular disease, and chronic kidney disease. Nevertheless, fungal infections, urinary tract infections, and ketoacidosis are the adverse effects that might happen during the SGLT2i treatment. Fungal infections are more common among patients treated with these medications, including vulvovaginal Candidiasis in women and balanitis or balanoposthitis in men. Given the difficulty of treating fungal infections in patients with co-occurring diseases, we recommend that ongoing supervision of patients treated with SGLT2i include prevention and early detection of fungal infections. Full article

In modern reliability and survival analysis, modeling bounded-lifetime data under complex sampling mechanisms remains a challenging yet practically significant problem, particularly in biomedical and engineering applications where experimental time and cost constraints are critical. This study develops a comprehensive inferential framework for the unit-Lindley (ULind) distribution under the improved adaptive progressive Type-II censoring (I-AP-CT2) strategy, a flexible design that ensures bounded test duration while accommodating progressive removal of experimental units. The proposed approach integrates both classical and Bayesian paradigms to enable robust estimation of the model parameter, reliability function, and hazard rate function. Maximum likelihood estimators are derived, and their asymptotic properties are established, with interval estimation constructed via normal approximation and log-transformed techniques. To address analytical intractability, a Bayesian framework via MCMC-based is formulated with a gamma prior, yielding credible and highest posterior density intervals. An extensive Monte Carlo simulation study is conducted to evaluate estimator performance under diverse censoring scenarios, demonstrating that Bayesian procedures consistently outperform their frequentist counterparts in terms of accuracy, stability, and interval efficiency. The practical relevance of the proposed methodology is illustrated through two real-world applications involving kidney dialysis survival data and petroleum engineering reliability data, representing critical domains where accurate modeling of failure behavior directly impacts clinical decision-making and industrial risk management. The findings highlight the flexibility of the ULind model in capturing complex hazard rate shapes and confirm the effectiveness of the I-AP-CT2 mechanism as a realistic and efficient experimental design. Full article

Type 2 diabetes mellitus (T2DM) is a progressive metabolic disease that necessitates individualized therapeutic strategies focusing on both glycemic control and the mitigation of comorbidities. In recent years, sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as a cornerstone of modern treatment due to their unique renal mechanism of action. This review summarizes the metabolic mechanisms, pleiotropic effects, and clinical significance of SGLT2 inhibitors in the management of T2DM. This review provides an updated overview of the metabolic and systemic effects of SGLT2 inhibition. By promoting glycosuria, SGLT2 inhibitors induce a negative energy balance that contributes to modest weight loss, improved body composition, and beneficial alterations in lipid metabolism. Beyond their metabolic effects, accumulating preclinical evidence suggests that SGLT2 inhibitors exert anti-inflammatory and antifibrotic actions, partly through modulation of macrophage polarization and attenuation of oxidative stress. The clinical utility of SGLT2 inhibitors is highlighted through the review of major cardiovascular and renal outcome trials, which confirm significant benefits in reducing heart failure hospitalizations and slowing the progression of chronic kidney disease. Finally, we integrate these findings into the context of the latest international guidelines while addressing safety profiles, the rationale for combination therapies, and the transition toward a personalized, risk-based management approach in T2DM. Full article

Polycystic kidney disease (PKD), the most common inherited kidney disorder, is characterized by progressive cyst growth and eventual organ failure. Although aberrant innate immune activation is a recognized contributor to PKD progression, the underlying molecular mechanisms remain incompletely defined. Here, we showed that Pkd1 deletion increased TLR2 and MyD88 mRNA expression in renal epithelial cells, indicating enhanced innate immune priming. In vivo, administration of Pam3CSK4 (PAM), a synthetic TLR2 agonist, preferentially amplified pro-inflammatory and pro-fibrotic responses in Pkd1^RC/RC mice compared with wild-type controls, despite inducing similar signaling responses in vitro. Acute PAM treatment for one week rapidly enhanced NF-κB activation in cyst-lining epithelial cells, increased renal inflammation and cell proliferation, and was associated with activation of mTOR signaling and upregulation of c-Myc and Wnt proteins. Sustained PAM treatment further accelerated cyst expansion and renal fibrosis in PKD mice. Importantly, the endogenous TLR2 ligands decorin and biglycan were markedly elevated in human PKD kidneys, supporting the translational relevance of enhanced TLR2 signaling in disease progression. Together, these findings suggest that TLR2 signaling is an important contributor to PKD progression and a potential therapeutic target. Full article

Background: Elevated anticardiolipin IgG (aCL IgG) has been reported in end-stage renal disease (ESRD), but its association with specific etiologies of kidney failure remains unexplored. The unique pathophysiology of diabetic–hypertensive nephropathy may be associated with a microenvironment that could potentially contribute to antiphospholipid antibody production and thrombotic complications. This study aimed to investigate whether aCL IgG elevation in hemodialysis (HD) patients is associated with combined diabetes–hypertension (DM + HTN) etiology and thrombocytopenia, thereby identifying a clinically distinct potential high-risk subgroup. In this hypothesis-generating study, we focused on within-HD patient comparisons rather than healthy controls. Methods: We enrolled 242 participants: 150 healthy controls (included only to establish local reference ranges) and 92 patients with maintenance HD. The study was conducted from 01 September to 20 November 2025 in Madinah, Saudi Arabia. Serum aCL IgG was measured by chemiluminescence immunoassay (positive ≥ 12 GPL units). Comprehensive hematological and biochemical parameters were analyzed. Multivariable logistic regression identified predictors of aCL positivity. Results: In the HD cohort, 21% demonstrated aCL positivity; this represents a substantially higher rate than the 2% observed in local healthy controls (p < 0.001). This elevation was not uniform across etiologies. Strikingly, 94.7% (18/19) of aCL-positive HD patients had DM + HTN aetiology, compared with only 17.8% of aCL-negative patients (p < 0.001). Thrombocytopenia was significantly more severe in aCL-positive patients (median platelets: 100 vs. 191 × 10⁹/L, p < 0.001). In multivariable analysis, DM + HTN etiology (HTN-alone vs. DM + HTN odds ratio [OR]: 0.0013, 95% confidence interval [CI]: 0.00002–0.0999, p = 0.003; confirmed by Firth’s penalized logistic regression sensitivity analysis, and lower platelet count (OR: 0.92 per 1 × 10⁹/L increase, 95% CI: 0.87–0.98, p = 0.006) independently predicted aCL positivity. Conclusions: These hypothesis-generating findings suggest a potential association between metabolic–vascular disease and antiphospholipid immunity in ESRD. Causality cannot be inferred from this cross-sectional design. At present, routine aCL screening is not recommended outside of research protocols; prospective studies are needed to confirm these associations. Full article

Background: Heart failure with reduced ejection fraction (HFrEF) and chronic kidney disease (CKD) are common in the growing population of elderly patients, yet little evidence specifically targeting this population exists. The purpose of this study is to analyze the effect of SGLT2 inhibition in this cohort. Methods: A single-center, real-world observational study was performed. Patients aged >75 with HFrEF and CKD and theoretical indication for sodium–glucose cotransporter 2 (SGLT2) inhibitors were enrolled. Results: A total of 173 patients were included, with a mean age of 84.7 years, mean left ventricle ejection fraction of 29.5% and estimated glomerular filtration rate of 45.9 mL/min/1.73 m². During a median follow-up of 39 months, 73 (42.2%) deaths from any cause and 95 (53.3%) major clinical events (composite of mortality and heart failure admission) were recorded. Multivariate Cox proportional hazards regression analyses were performed to identify associated variables, and SGLT2 inhibition showed to be a protective factor for the mortality endpoint (hazard ratio 0.324 [0.117–0.894]). Male sex was shown to be a risk factor for both endpoints, diabetes mellitus for the mortality endpoint and diuretic use for the major clinical event endpoints. Conclusions: In a real-world study, treatment with SGLT2 inhibitors in elderly patients with HFrEF and CKD was associated with a lower rate of all-cause mortality. Full article

IgA nephropathy is the most common primary glomerulonephritis worldwide and a leading cause of chronic kidney disease and kidney failure, with geographic and ancestral variation and a course ranging from asymptomatic urinary abnormalities to progressive loss of kidney function. This narrative review links the multi-hit model to risk stratification, biomarkers, current management, and emerging therapies, and highlights implementation gaps. Risk assessment is longitudinal, prioritizing proteinuria and estimated glomerular filtration rate trajectories and integrating Oxford MEST-C, prediction tools, and biomarker and multi-omics approaches, while recognizing limitations in histologic reproducibility and model calibration. Current management is anchored in optimized supportive care aimed at sustained proteinuria reduction and kidney protection, including intensive blood pressure control with maximal tolerated renin–angiotensin system blockade, dietary sodium restriction and lifestyle measures, and sodium–glucose co-transporter 2 inhibitors for eligible patients. For selected higher-risk patients with persistent proteinuria despite optimized supportive care, immunomodulatory strategies are discussed, including systemic corticosteroids and targeted-release budesonide (Nefecon), emphasizing structured toxicity risk mitigation and cautioning against assuming interchangeability among alternative oral budesonide formulations. Emerging therapies are organized around mechanism-aligned targets across the BAFF/APRIL axis, complement pathways, and endothelin-based approaches, with growing interest in sequencing and combination regimens layered on supportive care. Key gaps include reliance on surrogate endpoints, limited long-term durability and safety data, and uneven evidence for special populations. Full article

Background/objectives: Gram-negative bacterial infections are associated with significant morbidity and mortality. This targeted literature review (TLR) aimed to descriptively synthesise safety outcomes reported for polymyxins, aminoglycosides, and imipenem/cilastatin/relebactum (IMI/REL) in adult patients with Gram-negative infections. Methods: A TLR was conducted to identify published literature from 2015 to 2025. A database search was conducted on 14 February 2025, using the OVID^® platform and grey literature search reviewed publications from the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) and Infectious Disease (ID) Week. Safety outcomes included nephrotoxicity, other toxicities (e.g., haematological, hepatological), renal impairment, treatment-related (i.e., explicitly related to the antimicrobial treatment or its complications) discontinuation, and treatment-related mortality. Results: Sixty-eight publications were included. Definitions of nephrotoxicity varied between publications; RIFLE and KDIGO classifications were typically used. Definitions of renal impairment included renal risk/injury/failure and acute kidney injury (AKI). Colistin (n = 63) showed nephrotoxicity rates of 30.8–56.4%; renal impairment of 15.0–53.8%; treatment-related discontinuation of 12.5–23.0%; and treatment-related mortality from 20.0 to 39.1%. Polymyxin B showed nephrotoxicity rates of 14.6–54.9%; renal impairment rates ranging from 5.3 to 58.1%; and treatment-related mortality of 7.0% (n = 1). Aminoglycoside data were limited (n = 2) but showed nephrotoxicity rates of 77.8% and renal impairment of 18.8%. IMI/REL (n = 6) demonstrated nephrotoxicity of 10.3–17.2%; renal impairment of 0.0–20.7%; treatment-related discontinuation of 0.0–2.3%; and treatment-related mortality of 0.0–0.7%. Conclusions: Polymyxins/aminoglycosides had more frequently reported safety events. Fewer safety events were reported for IMI/REL across studies. These findings support the clinical use of IMI/REL and may inform Health Technology Assessment (HTA) decisions. Full article

Background: The optimal method of starting maintenance haemodialysis (HD) in patients with kidney failure is not known. We have compared early treatment characteristics, blood pressure trajectories, and selected dialysis-related safety events in patients who started HD using a stepped and phased approach, with those who received conventional care. Method: A single-centre cohort feasibility study was conducted. Participants with kidney failure, about to start maintenance HD, were enrolled prospectively (intervention arm). They started treatment on a novel regime comprising four pre-specified incremental steps (Phases 1 to 4) over 14 weeks. They were matched using propensity scores with historical controls: patients who had previously started HD on a three-times weekly basis from the outset (control arm). Results: The final cohort comprised 15 and 29 participants in the intervention and control arms respectively (1:2 ratio; one control excluded after matching). Intervention group participants were slightly older with a higher proportion of men. The rate of decline in blood pressure was slower in the intervention group. There were also signals for fewer events of intra-dialytic hypotension (211 vs. 379 per 100 person-year), infections not requiring admission (56 vs. 114 per 100 person-year) and loss of vascular access (56 vs. 79 per 100 person-year) in intervention group. There was a signal for higher incidence of severe hypertension (systolic BP ≥ 180 or diastolic BP ≥ 110 mmHg) in the intervention group. Hospitalisation rates were similar; there were no deaths and one non-fatal major cardiac event (MACE) in the intervention group, and one death and no MACE in the control group. Conclusions: Implementing a short transitional regime of incremental HD may be possible in clinical settings, potentially helping to reduce the gradient of physiological change and burden of early treatment. The findings of this feasibility study are exploratory, and fully powered randomised controlled trials are needed to establish the efficacy and safety of such a programme. Full article

Background: Earlier studies in patients with end-stage renal dysfunction (ESRD) reported no significant difference in long-term outcomes between mechanical and tissue valves after valve surgery, largely due to the limited life expectancy of this population. As survival in patients with ESRD has improved in recent years, this study evaluated whether increased life expectancy affects long-term outcomes according to valve type in patients with ESRD undergoing aortic valve replacement (AVR) using a nationwide cohort. Methods: We analyzed data from the Korean National Health Insurance Service database from January 2005 to December 2021. Among 474 patients with ESRD who underwent AVR, 279 received tissue valves and 195 received mechanical valves. Propensity score matching was performed to balance baseline characteristics, yielding 99 matched patient pairs. Results: In the matched cohort, early mortality (within 30 days) was significantly higher in the tissue valve group (16.2% vs. 4.0%; p = 0.008). However, long-term survival rates at 1, 5, and 10 years did not differ significantly between the groups (all p > 0.05). Stratification by operative era (2005–2013 vs. 2014–2021) similarly showed no significant impact of valve type on survival despite temporal advances in care. Conclusions: Long-term survival and complication rates after AVR in patients with ESRD were comparable between mechanical and tissue valves across operative eras. Valve selection should be guided by shared decision-making, incorporating individual life expectancy and comorbidity profiles rather than assuming mechanical valves as the default option. Full article

Background/Objectives: Nurses and dialysis technicians are primarily responsible for cannulation in in-center and satellite dialysis units. Despite being a core component of hemodialysis care, existing clinical guidelines offer limited standardization, resulting in practice variability across facilities. Therefore, clinical expertise and adherence to consistent standards are essential to ensure safe and effective vascular access management. The study aimed to investigate the variables related to patients and nurses that contribute to unsuccessful vascular access cannulations, as well as the actions taken in response to cannulation failure, in a tertiary dialysis center in the Eastern Region of Saudi Arabia. Methods: This retrospective analytic study reviewed the records of 228 adult hemodialysis patients at King Fahad Military Medical Complex from 2020 to 2024, analyzing demographic, clinical, vascular access, and nursing variables associated with cannulation failure using descriptive statistics, the chi-square test, and t-tests. Ethical approval was obtained, and data were de-identified and manually extracted from nursing and dialysis documentation. Results: Most patients had hypertension and diabetes, with significant comorbidity burdens. Infiltration (61%) and clot formation (30.7%) were the primary complications of cannulation failure. Significant associations emerged with recurrent stroke and peripheral vascular disease, but not with nurse or patient demographics, suggesting vascular factors outweigh staff variables in cannulation risk. Cannulation failures were most common in patients with vascular comorbidities, while staff experience and education had no significant impact. Conclusions: Recommendations include implementing tailored protocols, providing ongoing nurse education, conducting systematic vascular assessments, and holding regular team reviews to enhance access outcomes and patient safety. Full article