Search Results (2,788)

Background: Sodium–glucose cotransporter-2 inhibitors (SGLT2is), initially developed as antihyperglycemic agents, have emerged as multifunctional therapeutics with profound cardiorenal and metabolic benefits. Their unique insulin-independent mechanism, targeting renal glucose reabsorption, distinguishes them from conventional antidiabetic drugs. Mechanisms and Clinical Evidence: SGLT2is induce glycosuria, reduce hyperglycemia, and promote weight loss through increased caloric excretion. Beyond glycemic control, they modulate tubuloglomerular feedback, attenuate glomerular hyperfiltration, and exert systemic effects via natriuresis, ketone utilization, and anti-inflammatory pathways. Landmark trials (DAPA-HF, EMPEROR-Reduced, CREDENCE, DAPA-CKD) demonstrate robust reductions in heart failure (HF) hospitalizations, cardiovascular mortality, and chronic kidney disease (CKD) progression, irrespective of diabetes status. Adipose Tissue and Metabolic Effects: SGLT2is mitigate obesity-associated adiposopathy by shifting macrophage polarization (M1 to M2), reducing proinflammatory cytokines (TNF-α, IL-6), and enhancing adipose tissue browning (UCP1 upregulation) and mitochondrial biogenesis (via PGC-1α/PPARα). Modest weight loss (~2–4 kg) occurs, though compensatory hyperphagia may limit long-term effects. Emerging Applications: Potential roles in non-alcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), and neurodegenerative disorders are under investigation, driven by pleiotropic effects on metabolism and inflammation. Conclusions: SGLT2is represent a paradigm shift in managing T2DM, HF, and CKD, with expanding implications for metabolic syndrome. Future research should address interindividual variability, combination therapies, and non-glycemic indications to optimize their therapeutic potential. Full article

Background/Objectives: Iron deficiency without anemia (IDWA) is common among female patients with chronic kidney disease (CKD), yet the clinical implications of iron therapy in this population remain uncertain. While iron supplementation is frequently used in anemic CKD patients, evidence regarding its outcomes in non-anemic, iron-deficient individuals is limited and conflicting. Methods: This retrospective cohort study utilized the multi-institutional TriNetX database to examine the 5-year outcomes of iron therapy in adult women with stage 3 CKD, normal hemoglobin (≥12 g/dL), normal mean corpuscular volume (MCV), and low serum ferritin (<100 ng/mL). Primary outcomes included all-cause mortality, major adverse cardiovascular events (MACE), acute kidney injury (AKI), pneumonia, progression to advanced CKD (estimated glomerular filtration rate ≤30 mL/min/1.73 m²), and gastrointestinal (GI) bleeding. Results: We identified 53,769 eligible non-anemic patients with stage 3 CKD, low serum ferritin levels, and normal MCV. Propensity score matching (1:1) was conducted on demographic variables to compare iron-treated (n = 6638) and untreated (n = 6638) cohorts. Over the 5-year follow-up, iron therapy in non-anemic females with stage 3 CKD, low ferritin levels, and iron supplementation was significantly associated with increased risks of MACE, AKI, pneumonia, CKD progression, and GI bleeding (log-rank p < 0.0001). No significant difference in all-cause mortality was observed. Data on transferrin saturation and the dosage of iron supplementation were unavailable. Conclusions: In non-anemic women with stage 3 CKD and low ferritin levels, iron supplementation was linked to increased MACE, renal, and pneumonia risks without evident survival benefits. These findings suggest that iron therapy in this group of patients may not confer cardiovascular benefit and may pose risks. Full article

Cardiovascular–Kidney–Metabolic (CKM) syndrome symbolizes a single pathophysiologic entity including obesity, type 2 diabetes, chronic kidney disease, and cardiovascular disease. These conditions altogether accelerate adverse outcomes when they coexist. Recent evidence has shown that the function of glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium–glucose cotransporter-2 inhibitors (SGLT2i) alleviate stress on multiple organs. SGLT2i has been demonstrated to benefit heart failure, hemodynamic regulation, and renal protection while GLP-1RA on the other hand has been shown to demonstrate a strong impact on glycemic management, weight loss, and atherosclerotic cardiovascular disease. This review will aim to understand and evaluate the mechanistic rationalization, clinical evidence, and the potential therapeutic treatment of SGLT2 inhibitors and GLP-1 receptor agonists to treat individuals who have CKM syndrome. This analysis also assesses whether combination therapy can be a synergistic approach that may benefit patients but is still underutilized because of the lack of clear guidelines, the associated costs, and disparities in accessibility. Therefore, in this review, we will be discussing the combination therapy’s additive and synergistic effects, current recommendations and clinical evidence, and mechanistic insights of these GLT2 inhibitors and GLP-1 receptor agonists in CKM syndrome patients. Overall, early and combination usage of GLP-1RA and SGLT2i may be essential to demonstrating a significant shift in modern cardiometabolic therapy toward patient-centered care. Full article

Recent studies have demonstrated that the development and progression of hypertensive kidney injury comprise not only elevated systemic blood pressure but also a complex interplay of cellular, molecular, and genetic mechanisms. In this report, we outline the key emerging pathways—ranging from dysregulated renin–angiotensin system signaling, oxidative stress, immune-mediated inflammation, and metabolic abnormalities to epigenetic alterations and genetic susceptibilities—that contribute to kidney damage in hypertensive conditions. In addition, we also discuss precision medicine approaches like biomarker-directed therapies, pharmacologically targeted therapies, and device-based innovations for modulating these pathways. This integrative review emphasizes the application of omics technologies and genetically guided interventions to better stratify patients and offer personalized care for hypertensive kidney disease. Full article

Viral outbreaks have caused significant mortality and economic losses in aquaculture, highlighting the urgent need for effective therapies and a deeper understanding of antiviral and immune mechanisms in key species. This study investigates the constitutive and virus-induced antiviral responses in juvenile rainbow trout (Oncorhynchus mykiss) following infection with viral hemorrhagic septicemia virus (VHSV). Trout (30 g) were infected by immersion with VHSV (TCID₅₀ = 10⁵ mL⁻¹) for two hours. Samples were collected at 24, 72, and 120 h post-infection to assess hematology, innate immunity, viral load, and transcriptomic response. At 24 h post-infection, no immune response or increase in viral load was detected, suggesting the host had not yet recognized the virus and was still in the incubation phase. By 72 h, viral replication peaked, with high viral loads observed in mucosal tissues (skin and gills) and immune organs (kidney, spleen, liver), alongside strong up-regulation of antiviral genes, such as viperin. This gene maintained high expression through the final sampling point, indicating its key role in the antiviral response. At this stage, reduced immune competence was observed, marked by elevated nitric oxide and circulating thrombocytes. At 120 h, modest increases in peripheral monocyte, plasma lysozyme, and peroxidase activity were detected; however, these responses were insufficient to reduce viral load, suggesting the resolution phase had not yet begun. In summary, while a limited immune response was observed by the end of the trial, the consistent antiviral activity of viperin from peak infection to 120 h post-infection underscores its importance in the defence against VHSV in rainbow trout. Full article

Background: Accumulating evidence indicates that SARS-CoV-2 infection results in long-term multiorgan complications, with the kidney being a primary target. This study aimed to characterize the long-term transcriptomic changes in the kidney following coronavirus infection using a murine model of MHV-1-induced SARS-like illness and to evaluate the therapeutic efficacy of SPIKENET (SPK). Methods: A/J mice were infected with MHV-1. Renal tissues were collected and subjected to immunofluorescence analysis and Next Generation RNA Sequencing to identify differentially expressed genes associated with acute and chronic infection. Bioinformatic analyses, including PCA, volcano plots, and GO/KEGG pathway enrichment, were performed. A separate cohort received SPK treatment, and comparative transcriptomic profiling was conducted. Gene expression profile was further confirmed using real-time PCR. Results: Acute infection showed the upregulation of genes involved in inflammation and fibrosis. Long-term MHV-1 infection led to the sustained upregulation of genes involved in muscle regeneration, cytoskeletal remodeling, and fibrotic responses. Notably, both expression and variability of SLC22 and SLC22A8, key proximal tubule transporters, were reduced, suggesting a loss of segment-specific identity. Further, SLC12A1, a critical regulator of sodium reabsorption and blood pressure, was downregulated and is associated with the onset of polyuria and hydronephrosis. SLC transporters exhibited expression patterns consistent with tubular dysfunction and inflammation. These findings suggest aberrant activation of myogenic pathways and structural proteins in renal tissues, consistent with a pro-fibrotic phenotype. In contrast, SPK treatment reversed the expression of most genes, thereby restoring the gene profiles to those observed in control mice. Conclusions: MHV-1-induced long COVID is associated with persistent transcriptional reprogramming in the kidney, indicative of chronic inflammation, cytoskeletal dysregulation, and fibrogenesis. SPK demonstrates robust therapeutic potential by normalizing these molecular signatures and preventing long-term renal damage. These findings underscore the relevance of the MHV-1 model and support further investigation of SPK as a candidate therapy for COVID-19-associated renal sequelae. Full article

The association between COVID-19 vaccination and thromboembolic events has garnered significant research attention, particularly with the advent of vaccines based on adenoviral vectors, including AstraZeneca’s and Johnson & Johnson’s vaccines. This review underscores the uncommon occurrence of venous thromboembolism (VTE), arterial thromboembolism (ATE), and vaccine-induced thrombotic thrombocytopenia (VITT) following COVID-19 vaccination. Although these complications are extremely rare compared to the heightened risk of thrombosis from COVID-19 infection, elements like age, biological sex, type of vaccine and underlying health conditions may contribute to their development. In addition, rare renal complications such as acute kidney injury and thrombotic microangiopathy have been documented, broadening the spectrum of potential vaccine-associated thrombotic manifestations. Current guidelines emphasize early detection, individualized risk assessment, and use of anticoagulation therapy to mitigate risks. Despite these events, the overwhelming majority of evidence supports the continued use of COVID-19 vaccines, given their proven efficacy in reducing severe illness and mortality. In addition, recent comparative data confirm that mRNA-based vaccines are associated with a significantly lower risk of serious thrombotic events compared to adenoviral vector platforms. Ongoing research is essential to further refine preventive and therapeutic strategies, particularly for at-risk populations. Full article

Background/Objectives: COVID-19 is a systemic viral infection that may lead to serious complications including acute kidney injury that requires kidney replacement therapy. The primary aim of this study was to evaluate urinary SerpinA3 (uSerpinA3) excretion as a biomarker of kidney recovery at 90 days, and the mortality in patients with critical COVID-19 and AKI requiring kidney replacement therapy (KRT). Methods: The study included patients with critical COVID-19 on invasive mechanical ventilation (IMV) requiring KRT. Blood and urine samples were obtained when KRT was initiated (day zero), and thereafter on days 1, 3, 7, and 14 post-replacement. uSerpinA3, kidney injury molecule-1 (uKIM-1), and neutrophil gelatinase-associated lipocalin (uNGAL) were measured in urine, and interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-α) in peripheral blood. In addition, metabolomics in sample days zero and 3, and in the survivors on sample day 90 was performed by employing gas chromatography coupled with mass spectrometry. Results: A total of 60 patients were recruited, of whom 29 (48%) survived hospitalization and recovered kidney function by day 90. In the survivors, 79% presented complete recovery (CRR) and the remaining (21%) recovered partially (PRR). In terms of uSerpinA3, levels on days 7 and 14 predicted CRR, with AUC values of 0.68 (p = 0.041) and 0.71 (p = 0.030), respectively, as well as mortality, with AUC values of 0.75 (p = 0.007) and 0.76 (p = 0.015), respectively. Among the other biomarkers, the excretion of uKIM-1 on day zero of KRT had a superior performance as a CRR predictor [(AUC, 0.71 (p = 0.017)], and as a mortality predictor [AUC, 0.68 (p = 0.028)]. In the metabolomics analysis, we identified four distinct profiles; the metabolite that maintained statistical significance in predicting mortality was p-cresol glucuronide. Conclusions: This study strongly suggests that uSerpinA3 and uKIM-1 can predict CRR and mortality in patients with critical COVID-19 and AKI requiring KRT. Metabolic analysis appears promising for identifying affected pathways and their clinical impact in this population. Full article

Introduction: Renal malacoplakia is a rare chronic granulomatous disease, often associated with immunosuppression and persistent Gram-negative infections, particularly Escherichia coli. Case Presentation: We present a case involving a 31-year-old woman with hypertension, gestational diabetes, and prior uterine curettage after labor induction for preeclampsia at 23 weeks. She developed urinary sepsis post-procedure. Imaging revealed bilateral nephromegaly, while laboratory tests showed acute kidney injury (KDIGO stage III), anemia, and thrombocytopenia. Blood and urine cultures grew Escherichia coli. Renal biopsy confirmed malacoplakia, demonstrating PAS-positive Michaelis–Gutmann bodies and Von Hansemann cells. The patient responded to prolonged antibiotic therapy and supportive care. Discussion and Conclusion: This case highlights the importance of considering renal malacoplakia in patients with atypical urinary tract infections and nephromegaly, particularly in obstetric settings. Histopathological confirmation is essential, and timely treatment with intracellularly active antibiotics can lead to favorable outcomes. Early diagnosis is critical to prevent irreversible renal damage. Full article

Diabetic nephropathy affects approximately 30–40% of individuals with diabetes mellitus (DM) and is a major contributor to end-stage renal disease (ESRD). While angiotensin II receptor blockers (ARBs) have long served as a standard treatment, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have recently gained attention for their renal and cardiovascular benefits. However, comparative real-world data on their long-term renal effectiveness remain limited. We conducted a retrospective, longitudinal study over a 2-year period to compare the impact of ARB monotherapy versus SGLT2i and angiotensin-converting enzyme inhibitor (ACEi) combination therapy on the progression of chronic kidney disease (CKD) in patients with DM. A total of 126 patients were included and grouped based on treatment regimen. Renal biomarkers were analyzed using t-tests and ANOVA (p < 0.01). Albuminuria was qualitatively classified via urinalysis as negative, level 1 (+1), level 2 (+2), or level 3 (+3). The ARB group demonstrated higher estimated glomerular filtration rate (eGFR) and lower serum creatinine (sCr) levels than the combination therapy group, with glycated hemoglobin (HbA1c), potassium (K⁺), and blood pressure remaining within normal limits in both cohorts. Albuminuria remained stable over time, with 60.8% of ARB users and 73.1% of combination therapy users exhibiting persistently or on-average negative results. Despite the expected additive benefits of SGLT2i/ACEi therapy, ARB monotherapy was associated with slightly more favorable renal function markers and a lower incidence of severe albuminuria. These findings suggest a need for further controlled studies to clarify the comparative long-term renal effects of these treatment regimens. Full article

Background: Intravenous vancomycin remains a key agent in the treatment of complex orthopedic infections, particularly those involving methicillin-resistant Staphylococcus aureus (MRSA). However, its use is associated with significant risks, most notably nephrotoxicity. Despite guideline recommendations, standardized dosing and monitoring protocols are often absent in orthopedic settings, leading to inconsistent therapeutic drug exposure and preventable adverse events. This study evaluated the clinical impact of implementing a structured standard operating procedure (SOP) for intravenous vancomycin therapy in orthopedic inpatients. Methods: We conducted a single-center, pre-post cohort study at a university orthopedic department. The intervention consisted of a standard operating procedure (SOP) for intravenous vancomycin therapy, which mandated weight-based loading doses, renal function-adjusted maintenance dosing, trough level monitoring, and defined dose adjustments. Patients treated before SOP implementation (n = 58) formed the control group; those treated under the SOP (n = 56) were prospectively included. The primary outcome was the incidence of vancomycin-associated acute kidney injury (VA-AKI) defined by KDIGO Stage 1 criteria. Secondary outcomes included therapeutic trough level attainment and infusion-related or ototoxic adverse events. Results: All patients in the post-SOP group received a loading dose (100% vs. 31% pre-SOP, p < 0.001). The range of measured vancomycin trough levels narrowed substantially after SOP implementation (7.1–36.2 mg/L vs. 4.0–80.0 mg/L). The proportion of patients reaching therapeutic trough levels increased, although this was not statistically significant. Most notably, VA-AKI occurred in 17.2% of patients in the control group, but in none of the patients after SOP implementation (0%, p = 0.0013). No cases of ototoxicity were observed in either group. Infusion-related reactions decreased after the implementation of the SOP, though not significantly. Conclusions: The introduction of a structured vancomycin protocol significantly reduced adverse drug events and improved dosing control in orthopedic inpatients. Incorporating such protocols into routine practice represents a feasible and effective strategy to strengthen antibiotic stewardship and clinical quality in surgical disciplines. Full article

Background and Aims: Sepsis-associated acute kidney injury (S-AKI) is common and is associated with poor outcomes. This prospective observational study aimed to assess the predictive value of four novel biomarkers—syndecan-1 (SDC1), neutrophil gelatinase-associated lipocalin (NGAL), proenkephalin (PENK), and presepsin (PSPN)—for renal outcomes and mortality in septic ICU patients. Methods: Serum biomarker levels were measured in serum samples collected at the time of sepsis diagnosis on the basis of the Sepsis-3 criteria. Acute kidney injury (AKI) was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, and patients were grouped by the presence of AKI, renal replacement therapy requirement (RRT), and intensive care unit (ICU) survival. Demographic, clinical, laboratory, and severity score data were compared between groups to evaluate the predictive performance of biomarkers and clinical parameters. Results: Of the 140 septic patients included, 55.0% developed AKI, 17.2% required RRT, and the ICU mortality rate was 50.0%. SDC1 was independently associated with both AKI (OR: 1.201; p = 0.024) and RRT initiation (OR: 1.260; p = 0.004). It also demonstrated the highest predictive performance for RRT (AUC: 0.715; p = 0.001) and a significant AUC for AKI evaluation (AUC: 0.659; p = 0.002). NGAL levels were significantly elevated in patients with AKI and higher SOFA scores but were not independently predictive. PENK and PSPN were not significantly associated with any renal outcome or mortality. The combined SOFA–SDC1 model improved discrimination for both AKI (AUC: 0.770) and RRT (AUC: 0.737), surpassing individual predictors. Conclusions: SDC1 emerged as the most reliable biomarker for assessing AKI and predicting the need for RRT, highlighting its potential role in early renal risk stratification among critically ill patients. Full article

Background: The Malnutrition Screening Tool (MST) is commonly used to identify malnutrition risk; however it has demonstrated poor sensitivity to detect malnutrition in inpatients with chronic kidney disease (CKD) and kidney replacement therapy (KRT) populations. Gastrointestinal symptoms, such as poor appetite, may better detect malnutrition. The accuracy of MST or other nutrition-related parameters to detect malnutrition in ambulatory patients with CKD stages 4–5 without KRT has not been evaluated. Methods: A single site retrospective audit of outpatient records from May 2020 to March 2025 was conducted. Patients with eGFR < 25 mL/min/1.73 m² without KRT who had both MST and a 7-point Subjective Global Assessment (SGA) within 7 days were included. Sensitivity, specificity, and ROC-AUC analyses compared nutritional parameters against SGA-defined malnutrition. Nutritional parameters tested included MST, hand grip strength, upper gastrointestinal symptom burden, poor appetite and a combination of some of these parameters. Results: Among 231 patients (68.8% male, median age 69 years, median eGFR 15), 29.9% were at risk of malnutrition (MST ≥ 2) and 33.8% malnourished (SGA ≤ 5). All potential screening tools had AUC ranging from 0.604 to 0.710, implying a poor-to-moderate discriminator ability to detect malnutrition. Combining HGS ≤ 29.5 kg or MST ≥2 demonstrated high sensitivity (95.5%) and negative predictive value (93.3%), but low specificity (33.3%) for detecting malnutrition, indicating this approach is effective for ruling out malnutrition but may over-identify at-risk individuals. Conclusions: MST and other tested tools showed limited overall accuracy to identify malnutrition. Using combined nutritional markers of HGS or MST score was the most sensitive tool for detecting malnutrition in this advanced CKD without KRT population. Full article

Cystinosis is a rare systemic disease characterized by the accumulation of cystine in tissues, leading to multi-organ damage. Infantile nephropathic cystinosis is the dominant and severe form of cystinosis with critical renal manifestations that require kidney transplantation at an early age if left untreated. Cysteamine, the lifelong cystine-depleting therapy, is the mainstay treatment of nephropathic cystinosis. Cysteamine prevents cystine crystal formation and delays disease progression. While the initially introduced cysteamine consists of an immediate-release (IR) formulation, a delayed-release (DR) formulation has been developed with a simplified dosing regimen (Q12H instead of Q6H) and an improved quality of life while maintaining comparable efficacy. Due to the rare incidence of the disease and lack of international guidelines, diagnosis and treatment initiation are oftentimes delayed, leading to a poor prognosis. Pediatric and adult nephrologists from Kuwait, Saudi Arabia, the United Arab Emirates (UAE), and Qatar, in addition to one international expert from Amsterdam, convened to share their clinical experience, reflecting on the challenges encountered and therapeutic approaches followed in the management of nephropathic cystinosis in the Gulf Cooperation Council (GCC) region. Experts completed a multiple-choice questionnaire and engaged in structured discussions, where they shed light on gaps and limitations with regard to diagnostic tests and criteria to ensure early diagnosis and timely treatment initiation. Based on available literature, experts suggested an algorithm to help guide nephropathic cystinosis management in the GCC. It is highly recommended for patients who do not tolerate IR-cysteamine and do not adhere to IR-cysteamine treatment to switch to DR-cysteamine. Given the systemic nature of the disease, a multi-disciplinary approach is required for optimal disease management. Full article