Search Results (10,684)

Kidney cells are exposed to a wide range of physiological and pathological stresses, including hormonal changes, mechanical forces, hypoxia, hyperglycemia, and inflammation. These insults can trigger adaptive responses, but when they persist, they can lead to organelle stress. Organelles such as mitochondria, the endoplasmic reticulum, and primary cilia sustain cellular metabolism and tissue homeostasis. When organelle stress occurs, it disrupts cellular processes and organelle communication, leading to metabolic dysfunction, inflammation, fibrosis, and progression of kidney disease. Sex and hormonal factors play a significant role in the development of renal disorders. Many glomerular diseases show distinct differences between the sexes. Chronic Kidney Disease is more common in women, while men often experience a faster decline in kidney function, partly due to the influence of androgens. Additionally, the loss of female hormonal protection after menopause highlights the importance of sex as a factor in renal susceptibility. This narrative review synthesizes preclinical evidence on how sexual dimorphism and sex hormones affect organelle stress in mitochondria, the endoplasmic reticulum, and primary cilia, from 33 studies identified through a non-systematic literature search of the PubMed database, to provide an overview of how these mechanisms contribute to sex-specific differences in kidney disease pathophysiology. Full article

Background/Objectives: Autosomal dominant polycystic kidney disease (ADPKD) is a major cause of end-stage kidney disease (ESKD), accounting for approximately 5–10% of patients receiving dialysis worldwide. The large and numerous cysts in the liver and kidneys cause abdominal distention and poor appetite. Previous studies showed that renal arterial embolization (RAE) reduces total kidney volume (TKV), increases appetite, and improves quality of life. This article aims to evaluate the efficacy of RAE in increasing psoas muscle (PM) and paraspinal muscle (PS) mass in patients with polycystic kidney disease. Methods: A retrospective study was conducted from May 2016 to December 2020. Thirty-five patients with PKD and ESKD who received RAE were enrolled. The clinical data, including age, sex, body weight, abdominal circumference, and laboratory results, including albumin, creatinine, estimated glomerular filtration rate, and dialysis vintage, were collected. TKV was calculated with the ellipsoid formula method, and muscle mass was measured with bilateral PM and PS areas at the third lumbar level. The associated clinical, laboratory, and imaging data were compared before and after RAE. Results: There were 19 females and 16 males with a mean age of 59.9 for the final analysis. There were significant changes between baseline and 3-month, 6-month, 12-month after RAE, such as a decrease in TKV (4684 ± 3361 vs. 4079 ± 3456, 3675 ± 3401, 2459 ± 1706 mL, all p < 0.001), an increase in the PM area (12.6 ± 5.8 vs. 13.3 ± 5.7, 14.7 ± 6.9, 14.3 ± 7.1 cm², all p < 0.05), but no difference in body weight, body mass index, albumin, hemoglobin, creatinine, or estimated glomerular filtration rate. The increase in the PM and PS was more obvious in the sarcopenic group than in the non-sarcopenic group in the 12-month follow-up (p = 0.001 and 0.016 vs. p = 0.205 and 0.259). Conclusions: RAE effectively reduces TKV, increases PM and PS mass, and serves as a candidate to reverse muscle loss in patients with PKD. Full article

Accumulating evidence suggests that exposure to pollution from environmental cadmium (Cd) contributes to diabetic kidney disease as indicated by albuminuria and a progressive decrease in the estimated glomerular filtration rate (eGFR). This study examined the effects of Cd exposure on eGFR and the excretion rates of albumin (E_alb) and β₂-microglobulin (E_β2M) in 65 diabetics and 72 controls. Excretion of Cd (E_Cd) was a measure of exposure, while excretion of N-acetylglucosaminidase (E_NAG) reflected the extent of kidney tubular cell injury. In participants with an elevated excretion of E_β2M, the prevalence odds ratios (POR) for a reduced eGFR rose 6.4-fold, whereas the POR for albuminuria rose 4.3-fold, 4.1-fold, and 2.8-fold in those with a reduced eGFR, diabetes, and hypertension, respectively. Using covariance analysis, which adjusted for the interactions, 43% of the variation in E_alb among diabetics could be explained by female gender (η² = 0.176), E_NAG (η² = 0.162), hypertension (η² = 0.146), smoking (η² = 0.107), and body mass index (η² = 0.097), while the direct contribution of E_Cd to E_alb variability was minimal (η² = 0.005). Results from a mediating-effect analysis imply that Cd could contribute to albuminuria and a falling eGFR through inducing tubular cell injury, leading to reduced reabsorption of albumin and β₂M. Full article

Background and Objectives: Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic kidney disease, and the only approved pharmacological therapy shown to slow disease progression is tolvaptan. This study presents a long-term observation of ADPKD patients treated at our center, focusing on changes in eGFR approximately one year before and at least 1 year after the initiation of tolvaptan therapy. Materials and Methods: A retrospective analysis of a cohort of ADPKD patients who have received tolvaptan treatment in our center. Results: In total, 20 patients were enrolled in the analysis. Their median time of observation since tolvaptan introduction was 23.5 months. No statistically significant difference was noted in the median monthly decrease in eGFR between the time prior to tolvaptan introduction and during tolvaptan therapy. Analysis of trajectories of eGFR in particular patients enabled the division of the cohort into three subgroups: beneficiaries (n = 7, 35%), stable (n = 8, 40%), and progressors (n = 5, n = 25%). Conclusions: Despite the low number of patients, together with a relatively short observation period, which are the main limitations of our study, our results suggest that, in real-world settings, the efficacy of tolvaptan may be lower than previously reported. There is an urgent need to identify factors responsible for the suboptimal effect of the medicine. Our findings underscore the need to re-evaluate the current inclusion criteria for tolvaptan, particularly in real-world settings where patient variability is broader than in controlled clinical trials. Tailoring treatment qualification to include more practical and region-specific factors may enhance therapeutic outcomes. Full article

Background: Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer subtype and, in most cases, it is incidentally diagnosed, as early-stage disease is often asymptomatic. Therefore, the identification of stable, noninvasive biomarkers is a major unmet clinical need. Urinary microRNAs (miRNAs) have emerged as promising candidates since they are extraordinarily stable in urine and show a close relationship with tumour biology. Methods: In this study, urinary expression levels of five miRNAs (miR-15a, miR-15b, miR-16, miR-210, and miR-let-7b) were analysed in RCC patients before surgery, 5 days after, and one month after surgery, and compared to healthy controls. Results: Non-parametric analyses revealed significant postoperative decreases for miR-15a (p = 0.002), miR-16 (p = 0.025), miR-210 (p = 0.030), and in the overall miRNA Sum (p = 0.002), suggesting that these miRNAs are directly linked to tumour presence. In the comparison between preoperative and one-month postoperative samples, miR-let-7b (p = 0.049) and the global miRNA Sum (p = 0.037) remained significantly reduced after intervention, indicating a partial normalisation of urinary miRNA profiles. Correlation analyses demonstrated positive associations between specific miRNAs and clinical parameters such as age, ischemia time, and surgical time, reinforcing their potential relevance to tumour biology and treatment response. Conclusions: These findings support urinary miRNAs as promising, minimally invasive biomarkers for ccRCC diagnosis and postoperative monitoring. Full article

Background/Objectives: Coronary artery disease (CAD) is highly prevalent in patients undergoing vascular surgery and is a major determinant of postoperative morbidity and mortality. Preoperative anemia is a well-recognized risk factor for adverse outcomes, including major adverse cardiac events (MACEs), but its independent impact in patients with CAD undergoing abdominal aortic aneurysm (AAA) repair remains unclear. Methods: We conducted a retrospective cohort study of 410 consecutive patients undergoing open AAA repair at a tertiary vascular center between 2023 and 2025. Preoperative anemia was defined as hemoglobin < 130 g/L and significant CAD as ≥70% luminal narrowing for non-left main disease or ≥50% for left main disease. The primary outcome was MACE (cardiovascular death, myocardial infarction, or stroke) during hospitalization. Baseline covariates included age, sex, diabetes mellitus (DM), chronic kidney disease (CKD), congestive heart failure (CHF), peripheral artery disease (PAD), and other relevant comorbidities. Multivariable logistic regression models were used to evaluate associations of anemia, CAD, and their interaction with MACE. Additionally, a composite risk group was created to examine MACE rates across mutually exclusive subgroups. Results: Among 410 patients, 314 (76.6%) had CAD and 116 (28.3%) had preoperative anemia. Overall, 67 patients (16.3%) experienced MACE. In the reduced model including only anemia and CAD, anemia remained a strong independent predictor of a MACE (OR 4.46, 95% CI 2.57–7.72, p < 0.001), and CAD was also independently associated (OR 2.20, 95% CI 1.00–4.72, p = 0.044). In the full multivariable model adjusting for DM, CHF, CKD, PAD, and age, anemia was the strongest predictor (OR 4.53, 95% CI 2.49–8.26, p < 0.001), while CAD showed a borderline association (OR 2.07, 95% CI 0.94–4.57, p = 0.071). Interaction analysis indicated no statistically significant modification in risk by the combination of anemia and CAD. The composite risk group variable was omitted due to collinearity with its components. Conclusions: Preoperative anemia, particularly in patients with CAD, is a significant and independent predictor of major adverse cardiac events following open AAA repair. These findings support the importance of early identification and correction of anemia before surgery to improve perioperative cardiac outcomes in this high-risk population. Full article

Although the SARS-CoV-2 pandemic no longer poses a global emergency, the virus continues to diversify and acquire immunoevasive properties. Understanding the molecular pathways that shape SARS-CoV-2 pathogenesis has become essential. In this paper, we summarize the most recent current evidence on how the spike protein structurally evolves, on changes in key non-structural proteins, such as nsp14, and on host factors, such as TMPRSS2 and neuropilin-1. These changes, together, shape viral entry, replication fidelity and interferon antagonism. Given the emerging Omicron variants of SARS-CoV-2, recent articles in the literature, cryo-EM analyses, and artificial intelligence-assisted mutational modeling were analyzed to infer and contextualize mutation-driven mechanisms. It is through these changes that the virus adapts and evolves, such as optimizing angiotensin-converting enzyme binding, modifying antigenic surfaces, and accumulating mutations that affect CD8⁺ T-cell recognition. Multi-omics data studies further support SARS-CoV-2 pathogenesis through convergent evidence linking viral adaptation to host immune and metabolic reprogramming, as occurs in myocarditis, liver injury, and acute kidney injury. By integrating proteomic, transcriptomic, and structural findings, this work presents how the virus persists and dictates disease severity through interferon antagonism (ORF6, ORF9b, and nsp1), adaptive immune evasion, and metabolic rewiring. All these insights underscore the need for next-generation interventions that provide a multidimensional framework for understanding the evolution of SARS-CoV-2 and guiding future antiviral strategies. Full article

Background: Sodium–glucose cotransporter 2 inhibitors (SGLT2 inhibitors), initially developed for glycemic control in type 2 diabetes, have demonstrated robust cardiovascular and renal benefits. Emerging evidence suggests that these agents may also affect valvular pathobiology, particularly in degenerative aortic stenosis (AS), through anti-inflammatory and antifibrotic mechanisms. Objectives: This study evaluated whether SGLT2 inhibitor use is associated with improved clinical outcomes in degenerative AS, including all-cause mortality and the need for SAVR or TAVR, recognizing that these endpoints represent surrogate rather than direct measures of valve hemodynamic progression. Methods: A retrospective cohort analysis was conducted using TriNetX, a federated electronic medical record-based research network. Diagnoses are captured using ICD-9/ICD-10-CM codes and medications using ATC codes. Adults with non-rheumatic AS were stratified by SGLT2 inhibitors use. Propensity score matching (1:1) was performed to balance baseline characteristics between treated and untreated groups (n = 10,912 per group). Primary outcomes included all-cause mortality, TAVR, and SAVR during follow-up. Echocardiographic parameters (AVA, Vmax, mean gradient) were not systematically available. Results: After adjustment for comorbidities, SGLT2 inhibitor use was independently associated with lower all-cause mortality (6.15% vs. 9.34% HR 0.595; 95% CI 0.552–0.641; p < 0.001), TAVR (2.81% vs. 2.89% HR 0.835; 95% CI 0.746–0.934; p = 0.002), SAVR (1.28% vs. 1.90% HR 0.514; 95% CI 0.442–0.599; p < 0.001), cardiac arrest (0.82% vs. 1.21% HR 0.71; 95% CI 0.582–0.867; p < 0.001), and end-stage kidney disease (0.40% vs. 1.0% HR 0.292; 95% CI 0.222–0.384; p < 0.001). Although these associations may suggest slower disease progression, interpretation is limited by the lack of systematic echocardiographic follow-up. Conclusions: In addition to their established benefits in heart failure and renal protection, SGLT2 inhibitors may have valve-preserving effects in degenerative AS. Because true hemodynamic progression could not be evaluated, these results should be viewed as associations with surrogate clinical endpoints. Prospective studies with standardized imaging are required to determine whether SGLT2 inhibition can directly alter the course of this currently untreatable disease Full article

Oxidative stress and inflammation are key drivers in the pathogenesis of various chronic diseases, including cardiovascular disease, neurodegenerative disorders, chronic kidney disease, and diabetes. This study evaluated the antioxidant and anti-inflammatory activities of SHE, CME, and FCME, all cultivated in northern Thailand. Human embryonic kidney cells (HEK293) were exposed to FeSO₄ to induce oxidative stress and to LPS to stimulate inflammation. Cell viability was assessed using the MTT assay, while intracellular ROS production was measured using the DCFH-DA. Lipid peroxidation was quantified using the thiobarbituric acid reactive substances assay, and the interleukin-6 (IL-6) release was determined by ELISAs. All extracts demonstrated low cytotoxicity; however, cell death increased at 48 h compared to 24 h. At 200 µg/mL, SHE, CME, and FCME significantly reduced the H₂O₂-induced ROS generation, with the combined treatment of SHE and FCME producing a more pronounced reduction than the individual treatments. Furthermore, the combination of SHE and FCME markedly decreased malondialdehyde (MDA) and IL-6 levels compared with other groups. These findings suggest that shallot and cha-miang extracts, particularly in combination, exhibit promising antioxidant and anti-inflammatory properties in kidney cell models. This combination could therefore be explored as a nutraceutical strategy for the prevention and management of chronic kidney disease, in which oxidative stress and inflammation play pivotal roles. Overall, our finding highlight the potential of the combined use of SHE and FCME as a functional ingredients in the food and pharmaceutical industries. Full article

Weight loss occurs with chronic kidney disease (CKD) and is present in the early stages. Growth differentiation factor 8 (GDF8), also known as myostatin, is a negative regulator of muscle growth, and circulating GDF8 concentrations are increased in people with CKD. The objective of this study was to evaluate if serum GDF8 concentrations in cats with early CKD are increased compared to healthy cats. Associations of GDF8 with age, sex, body weight, body condition score (BCS), muscle condition score (MCS), and selected renal parameters were also examined. Serum GDF8 in healthy (n = 10), International Renal Interest Society (IRIS) stage 1 CKD (n = 5), and IRIS stage 2 CKD (n = 10) cats was quantified using a commercially available sandwich ELISA. GDF8 was not different amongst healthy cats (2137 ± 740 pg/mL) and cats with IRIS stage 1 (1785 ± 530 pg/mL) and IRIS stage 2 (1961 ± 638 pg/mL; p = 0.608) CKD. GDF8 was moderately correlated with MCS (r_s = 0.517, 95% CI 0.006–0.814, p = 0.049) and inversely correlated with age (r = −0.429, 95% CI −0.705 to −0.041, p = 0.032), but no association was found with the selected renal parameters, body weight, or BCS. Full article

Chronic kidney disease (CKD) is a progressive disease in which accurate estimation of glomerular filtration rate (GFR) is essential for staging and guiding therapy. Serum creatinine is widely used but influenced by non-renal factors, while cystatin C and β2-microglobulin (β2M) may provide complementary information related to filtration and tubular or inflammatory factors. This study compared the discriminatory performance of creatinine, cystatin C and β2M for separating CKD stage 3 from stage 4 within the 2021 CKD-EPI eGFR framework in 45 adults with CKD stages 3–4. CKD stage classification was defined using the 2021 CKD-EPI creatinine and creatinine–cystatin C equations (eGFRcr, eGFRcr–cys) with a threshold of 30 mL/min/1.73 m². Receiver operating characteristic (ROC) analysis evaluated each marker’s ability to distinguish moderate from severe CKD. Creatinine showed high diagnostic accuracy (AUC up to 0.98). Cystatin C achieved 100% specificity at the optimal cut-off for severe CKD and showed comparable diagnostic accuracy to creatinine under the eGFRcr–cys framework (AUC 0.978 vs. 0.957). β2M demonstrated AUCs up to 0.97, with sensitivity and specificity above 90%. These findings support a multi-marker evaluation within the 2021 CKD-EPI-based staging, rather than validation against measured GFR. Larger studies incorporating measured GFR and relevant clinical confounders are warranted. Full article

Background/Objectives: Diabetes mellitus and hypertension are the first and second most common causes of chronic kidney disease, respectively. Despite improvements in elucidating the pathophysiology behind these diseases and the expansion of the therapeutic armamentarium, the knowledge about the implicated genes, epigenetics, and biological pathways is limited. Methods: We sought to define diabetic nephropathy-specific and hypertensive nephropathy-specific gene signatures in human glomeruli through computational systems biology approaches. Results: Gene expression data of human glomeruli from patients with diabetic kidney disease (DKD) and hypertensive nephropathy (HTN) were collected and compared to gene expression patterns from healthy kidneys. Pathways were identified with functional enrichment analysis of DEGs. Transcription factor enrichment analysis, protein–protein interaction network expansion, and kinase enrichment analysis were also performed. Finally, novel drugs and small-molecule compounds that may reverse the kidney-specific phenotype of these disorders have been identified. Conclusions: These data suggest putative expansion of the therapeutic armamentarium in DKD and HTN, underscoring that understanding the molecular mechanisms occurring within tissue in kidney diseases may guide personalized therapy. Full article

This systematic review examines chronic kidney disease-associated pruritus (CKD-aP) as a complex clinical manifestation in patients undergoing hemodialysis. Traditionally considered a secondary symptom of end-stage renal disease, emerging evidence now positions CKD-aP as a multidimensional disorder with substantial pathogenic influence on patient outcomes. Using the PRISMA 2020 methodology, we critically evaluated 54 peer-reviewed studies published between 2020 and 2025. Our synthesis highlights a convergence of five mechanistic frameworks underpinning CKD-aP: elevated levels of uremic toxins originating from gut microbial dysbiosis, immune activation driven by IL-31 and other pro-inflammatory cytokines, heightened peripheral and central neural sensitization, dysregulation of endogenous opioid receptor pathways favoring μ-receptor activation, and xerosis-related epidermal barrier dysfunction. These mechanisms contribute to a systemic cycle of microinflammation, pruritogenic signaling, and neural hyperexcitability. We also identified and compared validated assessment tools—including the NRS, VAS, Skindex-10, and the UP-Dial scale—that facilitate standardized quantification of disease burden. While available treatments such as gabapentinoids and phototherapy offer partial relief, targeted therapies—including κ-opioid receptor agonists—represent a major advancement, although long-term effectiveness and accessibility remain under investigation. Growing scientific consensus establishes CKD-aP as a priority therapeutic target in hemodialysis care, underscoring the need for integrated, mechanism-based management strategies to improve quality of life and clinical outcomes. This work represents a narrative systematic review, integrating evidence from mechanistic, translational, and clinical studies to critically examine the biological pathways underlying CKD-associated pruritus. Full article

Objective: Diabetic kidney disease (DKD) is characterized by podocyte injury and impaired autophagy. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) exhibit therapeutic potential for DKD, yet their mechanisms remain unclear. This study investigated whether BMSC-Exos restore podocyte autophagy via the miR-143-3p/Bcl-2/Beclin1 axis to delay DKD progression. Methods: A high-glucose (HG)-induced podocyte injury model was established using mouse podocytes (MPC5). Autophagy-related proteins (Beclin1, Bcl-2, LC3) and the injury marker desmin were analyzed by Western blot and immunofluorescence (IF). High-throughput sequencing identified BMSC-Exos-enriched miRNAs, with the miR-143-3p/Bcl-2 targeting relationship validated by dual-luciferase reporter assays. BMSCs transfected with miR-143-3p mimic or inhibitor were used to assess exosomes effects on autophagy and podocin expression. In vivo, DKD mice received tail vein injections of modified BMSC-Exos, followed by evaluation of physiological parameters, biochemical indices, and renal histopathology. Results: BMSC-Exos were successfully isolated and characterized. Fluorescence microscopy confirmed exosomes internalization by HG-treated MPC5 cells. BMSC-Exos upregulated Beclin1 and LC3-II while downregulating Bcl-2 and desmin, indicating enhanced autophagy. High-throughput sequencing revealed miR-143-3p enrichment in BMSC-Exos, and Bcl-2 was confirmed as a direct target of miR-143-3p. Exosomes from miR-143-3p mimic-transfected BMSCs further promoted autophagy and podocin expression. In DKD mice, BMSC-Exos reduced blood glucose, urinary albumin-to-creatinine ratio (UACR), and ameliorated renal damage, whereas miR-143-3p inhibition attenuated these effects. Conclusions: BMSC-Exos deliver miR-143-3p to target Bcl-2, thereby activating Beclin1-mediated autophagy and ameliorating DKD. This study elucidates a novel autophagy regulatory mechanism supporting BMSC-Exos as a cell-free therapy for DKD. Full article

Background/Objectives: Kidney donation remains a critical component of addressing end-stage renal disease. This study examines differences in awareness, willingness to donate, and concerns related to kidney donation among medical and non-medical university students. By comparing these groups within the context of Croatia’s presumed-consent system for organ donation, the study provides insights into how educational backgrounds shape attitudes in a setting with high transplantation rates but limited data on young adults. Methods: A cross-sectional observational study targeted at medical and non-medical university students in Croatia. Data were collected from 640 participants via a self-administered, close-ended, structured questionnaire with 33 items divided across three sections. Responses were analyzed using IBM SPSS Statistics program (v. 30.0), to identify significant differences. Due to the cross-sectional design, causal relationships could not be inferred. Results: Overall, 190 students (28.7%) reported willingness to donate a kidney during their lifetime, which was more common among medical students (N = 59; 39.0%) than non-medical students (N = 131; 26.8%). Collectively, willingness to donate postmortem was high in both groups (N = 527; 82.3%), as was willingness in a brain-dead state (N = 448; 70.0%). Medical and non-medical students mostly cited perceived health risks as a concern and concerns related to surgical complications. Regarding information sources, 33.2% of students reported inadequate knowledge of kidney donation, with social media and internet searches cited more frequently than healthcare professionals. Conclusions: Our findings indicate that medical and non-medical students exhibit distinct gaps in knowledge, risk perception and willingness toward kidney donation. Within Croatia’s presumed-consent framework, these findings highlight the importance of targeted educational strategies to support informed decision-making among future generations. Full article