Search Results (161)

Background/Objectives: Esaxerenone is a non-steroidal mineralocorticoid receptor antagonist (MRA) with potent cardiorenal protective effects. However, the clinical effects of switching from eplerenone to esaxerenone in patients with chronic heart failure complicated by hypertension remain unclear. This study investigated the effects of switching from eplerenone to esaxerenone on blood pressure, heart failure biomarkers, renal function, and the renin–angiotensin–aldosterone system (RAAS). Methods: A total of 156 patients with chronic heart failure and hypertension who had been receiving eplerenone for more than one year were prospectively enrolled. Eplerenone was switched to esaxerenone, and the patients were followed for 6 months. Blood pressure, heart rate, brain natriuretic peptide (BNP), renal function, urinary albumin-to-creatinine ratio (UACR), plasma renin activity (PRA), plasma aldosterone concentration (PAC), and urinary osmolality (U-OSM) were evaluated. Results: Following the switch to esaxerenone, systolic and diastolic blood pressure significantly decreased (both p < 0.001), whereas heart rate remained unchanged. BNP levels significantly decreased at 3 and 6 months (p = 0.008 and p = 0.002, respectively). Serum creatinine decreased (p = 0.017), estimated glomerular filtration rate increased (p = 0.028), and UACR significantly decreased at both time points (both p < 0.001). PRA and PAC significantly increased after switching (both p < 0.05), whereas angiotensin II levels remained unchanged. U-OSM significantly decreased (p = 0.01 and p = 0.002 at 3 and 6 months, respectively). No major cardiovascular events or severe adverse events were observed. Conclusions: In patients with chronic heart failure and hypertension, switching from eplerenone to esaxerenone was associated with reductions in blood pressure, BNP, UACR, and urinary osmolality, together with improvements in renal function. These findings suggest favorable physiological changes following the switch from a steroidal to a non-steroidal mineralocorticoid receptor antagonist, although confirmation in randomized controlled studies with clinical outcome measures is warranted. Full article

Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease and end-stage kidney disease worldwide, imposing a major clinical and economic burden. Conventional diagnostic markers, including albuminuria and estimated glomerular filtration rate (eGFR), have limited sensitivity and specificity for early disease detection and for accurately predicting progression. Increasing evidence suggests that DKD involves complex glomerular, tubular, inflammatory, fibrotic, and oxidative stress pathways that precede overt clinical manifestations. Consequently, considerable attention has focused on identifying novel noninvasive biomarkers, particularly urinary biomarkers, alongside selected circulating biomarkers and emerging multi-omics signatures. Proteins, peptides, extracellular vesicles, and RNA-based biomarkers have demonstrated promising diagnostic and prognostic potential for detecting early renal injury, improving risk stratification, and monitoring therapeutic response. This review summarizes recent advances in biomarker research for DKD, highlighting emerging molecular and omics-based signatures that may complement conventional markers in improving early detection, prognostic assessment, and disease phenotyping. While numerous biomarkers have shown promising associations with renal outcomes and disease progression, the majority remain investigational. Their translation into routine clinical practice will depend on rigorous external validation, standardized analytical methods, and demonstration of added value beyond established clinical measures. Full article

Background/Objectives: Cervical cancer is mainly driven by persistent infection with high-risk human papillomaviruses (HPV), particularly HPV16 and HPV18. Despite advances in cytology, HPV-DNA testing and vaccination, challenges remain in the triage of HPV-positive individuals, prognostic stratification and prediction of treatment response. Non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs and circular RNAs, together with host genetic factors influencing ncRNA expression and emerging lncRNA-encoded peptides, are increasingly recognized as regulators of HPV-associated carcinogenesis. This review summarizes their biological and potential clinical relevance. Methods: A structured literature search was conducted in PubMed and Scopus. Eligible studies included experimental, clinical, observational, genomic and translational investigations on ncRNA dysregulation, circulating or exosomal ncRNAs, treatment-response signatures, host genetic variation and lncRNA-encoded peptides in HPV-associated cervical precancer and cancer. Results: HPV oncoproteins can reshape host ncRNA networks through transcriptional and epigenetic mechanisms. Several miRNAs, lncRNAs and circRNAs are involved in cell-cycle control, apoptosis, senescence, epithelial–mesenchymal transition, immune regulation, DNA repair and treatment resistance. Circulating, exosomal and urinary ncRNA signatures have shown diagnostic or prognostic potential in exploratory cohorts. Specific lncRNAs, including ENSG00000267838/lnc-LENG9-5 and lncRNA-EME1, have been associated with chemoradiotherapy response and radioresistance. The lncRNA-encoded peptide TUBORF represents a novel preclinical therapeutic candidate, while genetic variation may further modulate lncRNA function in HPV-related cervical cancer. Conclusions: ncRNAs are promising candidates for risk stratification, non-invasive diagnosis, treatment-response prediction and therapeutic development in HPV-associated cervical disease. However, evidence remains exploratory, requiring prospective multicentre validation and standardized workflows before clinical implementation. Full article

Background: Vitamin D, through its role in antimicrobial peptide (AMP) expression, may influence innate immunity and inflammation in urinary tract infections (UTIs). This study evaluated its role in patients with vesicoureteral reflux (VUR) and its contribution to the pathophysiology of reflux nephropathy (RN). Methods: We conducted a cross-sectional observational study of 25 pediatric patients with VUR, representing a subgroup analysis of a larger cohort examined in a previous study. We determined patients’ vitamin D status, correlated it with recurrent UTIs and RS, and explored its relationship with urinary LL-37, NGAL, and IL-6 levels as markers of innate immune function. Results: Serum vitamin D levels ranged from 10.7 to 123.2 ng/mL (mean 39.5 ng/mL); 12% had deficiency and 20% had insufficient levels. Low vitamin D levels were detected in patients with more than five acute pyelonephritis (APNs), with a mean value classified as insufficient (27.3 ng/mL). Patients with RS had a lower mean vitamin D level compared to those without (30.51 ng/mL vs. 41.23 ng/mL), though the difference was not statistically significant (p = 0.39). No significant associations were found between vitamin D and urinary IL-6 or NGAL levels. A strong positive correlation was observed between vitamin D and urinary LL-37/creatinine (r = 0.78, r² = 0.61). Conclusions: Vitamin D appears to influence the frequency of UTIs and the development of RS, primarily by modulating LL-37 secretion, suggesting a possible role in the pathophysiology of RN. Full article

Background: Ectopic fat deposition has been demonstrated to play a critical role in the onset and progression of renal dysfunction. However, research on renal parenchymal fat deposition and its association with renal dysfunction in type 2 diabetes mellitus (T2DM) remains limited, particularly regarding its association with early kidney injury. The present study aimed to further investigate the relationship between renal fat fraction (FF) and biomarkers of kidney injury, thereby providing new evidence for the potential link between intrarenal fat accumulation and early renal impairment in T2DM. Methods: This cross-sectional study enrolled 60 patients with T2DM. Renal FF was quantitatively assessed using magnetic resonance imaging (MRI). Clinical characteristics, body composition parameters, and biochemical indices were collected. Levels of kidney injury biomarkers, including tumor necrosis factor receptors 1 (TNF-R1), tumor necrosis factor receptors 2 (TNF-R2), chitinase-3-like protein 1 (YKL-40), and kidney injury molecule-1 (KIM-1), were measured using enzyme-linked immunosorbent assay (ELISA). To evaluate the correlations between fat distribution and inflammatory biomarkers, Pearson correlation analysis was performed. Furthermore, linear regression analysis was conducted to explore the associations between renal FF and kidney injury biomarkers with adjustments for potential confounders such as smoking status, diabetes duration, and visceral fat. Lasso regression was used to screen variables. Results: The results demonstrated that renal FF was significantly positively correlated with serum YKL-40 (r = 0.3, p = 0.021), TNF-R1 (r = 0.246, p = 0.042), and urinary KIM-1 (r = 0.396, p = 0.004), indicating a close association between renal fat accumulation and early kidney injury biomarkers. In regression analyses adjusted for age, sex, and duration of diabetes, the associations between renal FF and these biomarkers remained significant. After further adjustment for potential confounders, including smoking history, alcohol consumption, hypertension, renin-angiotensin-aldosterone system (RAAS) inhibitors, sodium-dependent glucose transporters 2 (SGLT2) inhibitors, glucagon-Like Peptide-1 (GLP-1) receptor agonists, and lipid-lowering drugs, renal FF remained significantly associated with TNF-R1 (β = 0.327, p = 0.015), KIM-1 (β = 0.352, p = 0.021), and YKL-40 (β = 0.275, p = 0.025). Moreover, even after additional adjustment for visceral fat, the associations of renal FF with TNF-R1 and KIM-1 persisted. After using the Benjamini–Hochberg procedure for false discovery rate, the relationship between renal FF and KIM-1 had a significant difference. Variables of age and gender were excluded to build the parsimonious modeling using Lasso regression. It suggested that renal fat accumulation may contribute to kidney injury independently of visceral adiposity. Conclusions: The study systematically demonstrates a significant association between renal FF and early biomarkers of kidney injury in T2DM, which may suggest the potential role of renal fat accumulation in the pathogenesis of diabetic nephropathy. These findings provide clinical data support for the development of a fat-targeted intervention study. Future research should further elucidate the long-term mechanistic role of renal FF in diabetic nephropathy, as well as its potential value in early diagnosis and therapeutic applications. Full article

Diabetes, a major global public health concern, requires early diagnosis and timely intervention. Glycated hemoglobin A1c (HbA1c) serves as a biomarker of glycemic management, with its levels showing a continuous relationship with the risk of developing diabetes. In this study, urinary proteome modifications were compared between each of the two patient groups with different HbA1c levels ([6.4 ± 0.7]% and [8.6 ± 1.6]%) and healthy controls. A total of 1954 and 5545 differentially modified peptides were identified in the two groups, respectively. Within each group, differentially modified peptides exhibiting changes from presence to absence or vice versa accounted for 48.8% and 86.5%, respectively. Additionally, results from the randomized grouping test indicated that at least 90.6% and 94.1% of these differentially modified peptides in each group were not randomly generated. In conclusion, urinary proteome modifications comprehensively and systematically reflect changes associated with elevated HbA1c levels, with distinct modification profiles corresponding to different HbA1c levels. These findings suggest that urinary proteome modifications have the potential to reflect HbA1c levels and offer a new perspective for research on the early diagnosis of diabetes. Full article

Background/Objectives: Adults with congenital heart disease (CHD) have a substantially higher risk of ischemic stroke than the general population. Circulating biomarkers such as N-terminal pro B-type natriuretic peptide (NT-pro-BNP), high-sensitivity C-reactive protein (hs-CRP), and microalbuminuria have been associated with adverse cardiovascular outcomes in CHD, but their role in predicting cerebrovascular events remains uncertain. Methods: Prospective cohort study including 372 adults with CHD [median age 34 years (IQR 23–42); 57.8% male] followed at a tertiary center between 2017 and 2022. Baseline assessments included demographic characteristics, CHD anatomical complexity, cardiovascular risk factors, NT-pro-BNP, hs-CRP, lipid profile, and 24-h urinary albumin excretion. The primary endpoint was incident ischemic stroke during a median follow-up of 6.3 years (IQR 3.9–8.3). Univariable Cox proportional hazards models were used to identify predictors of stroke. Results: During follow-up, 13 patients (3.5%) experienced ischemic stroke. Patients with stroke were significantly older [51 (46–64) vs. 30 (23–40) years; p < 0.001] and had a higher prevalence of dyslipidemia (61.5% vs. 15.0%; p < 0.001). NT-pro-BNP levels were markedly higher in patients with stroke [369 (218–604) vs. 64 (21–172) pg/mL; p < 0.001]. No significant differences were observed between groups in renal function parameters, hs-CRP, thyroid-stimulating hormone, or urinary albumin excretion rate. In Cox analyses, older age and dyslipidemia were the strongest predictors of stroke (p < 0.001). Arterial hypertension, diabetes mellitus, and higher NT-pro-BNP levels were also associated with increased stroke risk (p < 0.05), whereas CHD anatomical complexity, NYHA functional class, and cyanosis were not. Conclusions: In adults with CHD, ischemic stroke was mainly associated with traditional cardiovascular risk factors and elevated NT-pro-BNP levels rather than anatomical disease complexity or functional status. Full article

Background/Objectives: Multidrug-resistant (MDR) Acinetobacter baumannii (Ab) has emerged as a significant bacterial pathogen responsible for nosocomial infections. The most common clinical manifestations of Ab infection include ventilator-associated pneumonia and catheter-related bloodstream/urinary infections. Given the extensive MDR phenotype of Ab, preventive vaccination strategies are crucial for protecting susceptible populations. Methods: We utilized immunoinformatics to identify candidate peptides containing both putative B- and T-cell epitopes from proteins associated with Ab pathogenesis. Subsequently, we designed novel Acinetobacter Multi-Epitope Vaccines (AMEVs), each comprising an Ab thioredoxin A (TrxA) leader protein, five to seven of the identified peptide antigens, and a C-terminal His(6x)-tag to facilitate protein purification. Results: Subcutaneous vaccination of C57BL/6 mice with AMEV1 or AMEV2, formulated with TiterMax adjuvant, conferred 60% and 80% protection, respectively, against intraperitoneal Ab challenge. AMEV vaccination induced a robust antibody response to each corresponding whole protein and most of its component peptides. We then constructed an improved vaccine, AMEV5, which included the Ab TrxA protein and seven confirmed B-cell epitope peptides. Subcutaneous immunization of BALB/c mice (n = 10 per group) with rAMEV5 emulsified in Adda03 adjuvant activated antigen-specific IL-5-secreting T cells and antibody-producing B cells. Evaluation of vaccine efficacy demonstrated that AMEV2- and AMEV5-immunized mice were protected from a lethal intraperitoneal Ab challenge, with survival rates of 70% and 90%, respectively. Conclusions: These study results provide insights into the application of reverse vaccinology to combat the rise of MDR Acinetobacter infection. Full article

Bladder cancer (BCa) is a major global urinary tract malignancy characterized by high incidence, frequent recurrence, and significant mortality. Early diagnosis is crucial for improving prognosis and minimizing invasive procedures; however, current standard techniques, cystoscopy and urine cytology, are limited by invasiveness, cost, low sensitivity, and subjectivity. This has spurred the development of non-invasive diagnostic strategies based on urine analysis. This review highlights five emerging approaches: AI-augmented urine cytology, genomic biomarker assays (e.g., PCR and NGS for mutations and copy-number variations), DNA methylation profiling, RNA biomarkers (mRNA, miRNA, lncRNA), and protein/peptide/metabolite detection utilizing ELISA, SERS, nanozymes, and mass spectrometry. We assess the diagnostic accuracy, innovations, and clinical potential of each, while addressing persisting issues such as lack of standardization, high costs, and insufficient sensitivity for early-stage lesions. Future directions include integrating multi-omics data with AI, advancing point-of-care devices, and conducting large-scale multicenter trials. Together, these developments promise to shift BCa management toward molecular-based early detection, enabling more precise, non-invasive, and personalized patient care. Full article

Before the American Heart Association introduced the cardiovascular–kidney–metabolic (CKM) syndrome concept in 2023, clinical care was largely organ-specific. This retrospective study analyzed diagnostic patterns and gaps in 406 patients with hypertension referred to and evaluated at the University Hospital Basel Hypertension Centre in 2017, 2019, or 2022 to identify blind spots in the assessment of cardio–kidney–liver–metabolic health. Electronic health records were used to assess CKM-relevant diagnostics, including lipid profiles, N-terminal pro-B-type natriuretic peptide (NT-proBNP), echocardiography, kidney function (estimated glomerular filtration rate: eGFR, urinary albumin-to-creatinine ratio: uACR), and hepatic assessment (Fib-4 score, abdominal ultrasound). Previously undetected conditions were identified according to contemporary criteria for dyslipidemia, chronic kidney disease (CKD), suspected heart failure (HF), diabetes, and suspected metabolic dysfunction-associated steatotic liver disease (MASLD). Although 94% of participants had laboratory data, key CKM parameters were inconsistently assessed. Of the participants, 39% had neither NT-proBNP measurement nor echocardiography, and 27% lacked hepatic ultrasound or sufficient data for Fib-4 calculation. Previously unrecognized comorbidities were common (suspected HF 21%, CKD 6%, suspected MASLD 3%). Lipoprotein(a) testing increased from 0% in 2017 to 23.7% in 2022, indicating growing awareness. Despite specialized care, diagnostic fragmentation persisted, underlining the need for systematic, interdisciplinary screening and informing the design of prospective registries such as the Swiss CKLM Registry to integrate patient-centered cardio–kidney–liver–metabolic care. Full article

This study investigates two graphene oxide (GO)-based coating architectures on urinary catheter substrates—layered (PEI+GO) and embedded (PEI/GO)—loaded with antimicrobial peptides (E14LKK and fLFB), with the aim of elucidating how coating structure governs peptide retention and release. Physicochemical and morphological characterization confirmed distinct coating architectures and thicknesses. Molecular dynamics simulations were employed to probe GO–peptide and PEI–peptide interactions, revealing weaker binding of fLFB to GO relative to PEI, consistent with enhanced peptide mobility. Antibacterial performance against Escherichia coli and Enterococcus faecalis was evaluated using agar diffusion assays as a comparative indicator of peptide release from surface-bound coatings. The layered PEI+GO–fLFB system exhibited the highest antibacterial activity, in agreement with simulation-predicted interaction energetics and structural fluctuations. Rather than targeting immediate clinical translation, this work provides mechanistic insight into how GO–polymer architecture modulates antimicrobial peptide availability, offering a molecular dynamics simulation-guided framework for the rational design of peptide-releasing antimicrobial coatings. Full article

Urinary gluten immunogenic peptides (u-GIPs) have been proposed as a complementary marker to classical intestinal permeability tests based on lactulose, mannitol, and the lactulose:mannitol ratio (LMR). However, the effects of gluten dose, urine collection interval, and sampling strategy on their performance remain insufficiently defined. This study evaluated these variables to support protocol standardization. Data from four standardized protocols including 46 healthy adults exposed to 0, 2, 4, or 10 g of gluten were analyzed. All participants ingested fixed doses of lactulose and mannitol. Urine was collected cumulatively (0–6 h and 0–15 h) or by individual voids. u-GIP levels were measured by lateral-flow immunoassay, and lactulose and mannitol by ion chromatography. u-GIP excretion showed a clear dose dependence. Lactulose excretion increased transiently only at the 10 g dose during the 0–6 h interval, while mannitol excretion and LMR were unaffected. The u-GIP excretion index showed linear proportionality at the 2 g and 4 g doses but exhibited saturation kinetics at the 10 g dose. The 4 g dose showed the lowest interindividual variability. Sampling strategies yielded equivalent results. A 4 g gluten challenge combined with a 6 h urine collection demonstrated effectiveness in healthy volunteers and may be suitable for clinical application. Further research involving larger cohorts of both healthy individuals and patients with intestinal hyperpermeability is required to validate this method. Full article

Background/Objectives: Advanced glycation end products (AGEs) and oxidative stress increase with aging and are implicated in Alzheimer’s disease (AD). We developed an anti-glycation blend using LC-MS-based screening and assessed its effects on oxidative and glycation-related biomarkers in humans. Methods: Twelve candidate compounds were screened in a BSA–glucose model using LC-MS peptide mapping to quantify lysine glycation and rank inhibitory activity. The top candidates were combined into a three-compound blend (quercetin, rutin, genistein). In a randomized, double-blind, placebo-controlled 3-month trial, older healthy adults (n = 30) and individuals with AD (n = 30) received anti-AGE blend (n = 15 in older group and n = 15 in AD group) or placebo (n = 15 in older group and n = 15 in AD group). Serum malondialdehyde and urinary Nε-(carboxymethyl)lysine were measured pre–post intervention. Pre/post and between-arm comparisons within each population were performed using REML ANOVA with Tukey post hoc tests. Serum MDA (malondialdehyde) and urinary CML (Nε-(carboxymethyl)lysine) were prespecified biomarker outcomes and are reported here as co-primary biomarker endpoints. No formal a priori sample size calculation was performed; the study size was feasibility-based. Results: LC-MS screening identified genistein, quercetin, and rutin as the most consistent inhibitors of glucose-driven BSA glycation. In older healthy adults, serum MDA decreased after anti-AGE supplementation (p < 0.001) and differed from the placebo (p < 0.01), while no change was observed within the placebo group (ns). In the AD cohort, MDA did not change significantly from baseline within either arm (ns), but post-intervention MDA was lower in anti-AGE than in the placebo (p < 0.05). Urinary CML was unchanged in older healthy adults (ns in both arms), whereas in AD, it decreased after anti-AGE supplementation (p < 0.01) and differed from the placebo (p < 0.05). Conclusions: A screening-guided anti-glycation blend supplementation was associated with changes in selected biomarkers in humans: MDA decreased across cohorts, while CML decreased selectively in AD. Larger trials with extended biomarker panels and LC–MS/MS confirmation are warranted. Full article

Complement activation has been implicated in many kidney diseases, but it remains unclear whether urinary complement-derived peptides reflect kidney function beyond albuminuria and predict disease progression. We analyzed mass spectrometry-based urinary peptidomics data from 10,939 individuals with chronic kidney disease and healthy controls. Fifty-eight complement-derived peptides were identified, predominantly from complement factor B (CFB) and C3. Of these, fifty-two were significantly related to estimated glomerular filtration rate (eGFR) independently of albuminuria, mostly inversely. Several C3- and CFB-derived peptides were also associated with specific kidney disease etiologies. In a longitudinal analysis of 3964 individuals (median follow-up 2.91 years), 18 of these peptides were significantly related to a major adverse kidney event (MAKE, defined as ≥40% eGFR decline, end-stage kidney disease or death) after adjustment for clinical covariates, indicating prognostic information beyond traditional risk markers. In the independent test cohort, combining these peptides in a machine learning-based model and adding the resulting risk score to clinical parameters significantly improved MAKE prediction (AUC 0.801 vs. 0.778, p = 0.031). Thus, urinary complement-derived peptides provide independent and clinically relevant information on kidney function and disease progression, supporting their potential value in the identification of high-risk patients and guiding more personalized therapy. Full article

Long COVID (LC) may involve endocrine dysfunction; however, the underlying mechanism remains unclear. To examine hypothalamic–pituitary responses in patients with LC, we conducted a single-center retrospective study of patients with refractory LC referred to our University Hospital who underwent anterior pituitary stimulation tests. Between February 2021 and November 2025, 1251 patients with long COVID were evaluated, of whom 207 (19%) had relatively low random ACTH or cortisol levels. Ultimately, 16 underwent anterior pituitary stimulation tests and were included. All tests were performed in an inpatient setting without exogenous steroids. Fifteen patients (six women, mean age 35.6 years) underwent corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), and gonadotropin-releasing hormone (GnRH) tests. All patients had mild acute COVID-19, eight had ≥2 vaccinations, and the mean interval from infection was 343 days. Frequent symptoms included fatigue (100%), insomnia (66.7%), headache (60.0%), anorexia/nausea (40.0%), and brain fog (40.0%). Mean early-morning cortisol and 24 h urinary free cortisol were 7.5 μg/dL and 41.0 μg/day, respectively. MRI showed an empty sella in one case. Peak hormonal responses were preserved (ΔACTH 247%, ΔTSH 918%, ΔPRL 820%, ΔFSH 187%, ΔLH 1150%); however, peaks were delayed beyond 60 min in ACTH (13%), LH (33%), and FSH (87%). Notably, significantly delayed elevations remained at 120 min in the responses of TSH (4.1-fold), PRL (1.8-fold), LH (9.3-fold), and FSH (2.8-fold), suggesting possible hypothalamic involvement, particularly in the gonadotropin responses. Additionally, serum IGF-I was lowered (−0.70 SD), while GH response (mean peak 35.5 ng/mL) was preserved by growth hormone-releasing peptide (GHRP)-2 stimulation. Low-dose hydrocortisone and testosterone were initiated for three patients. Although direct viral effects and secondary suppression have been proposed, our findings may suggest that, at least in part, the observed response characteristics are consistent with functional secondary hypothalamic dysfunction rather than irreversible primary injury. These findings highlight the need for objective endocrine evaluation before initiating hormone replacements. Full article