Search Results (3,631)

The influence of gaseous components of tobacco smoke, e-cigarettes, and air pollutants on the development of glomerulonephritis has been the subject of numerous studies in recent years. Glomerulonephritis (GN) often leads to progressive kidney damage and chronic kidney disease (CKD), which is a global health problem. Genetic and autoimmune factors have been shown to contribute to their development. Yet, increasing attention is being given to environmental and lifestyle-related risk factors. This paper summarizes how specific substances found in tobacco smoke, e-cigarette smoke, and air pollutants contribute to the development and progression of GN. Particular emphasis is placed on substances such as formaldehyde, heavy metals, and particulate matter, which have been shown to trigger oxidative stress, immune dysregulation, and endothelial dysfunction. A clear understanding of the contributions of those agents to kidney inflammation is crucial for developing preventive strategies and improving public health awareness. We also highlight gaps in current research and suggest directions for future investigation. Understanding consequences of cigarette smoking should be promoted to encourage people to reduce their exposure to cigarette smoke, which could prevent many diseases. Full article

Background/Objectives: Chronic kidney disease (CKD) is a global public health concern, posing significant diagnostic and management challenges in primary care. Estimated glomerular filtration rate (eGFR) is central to CKD staging, yet different estimating equations may yield substantially different stage classifications when applied to the same population. This study aims to compare the eGFR-based CKD stage classification and stage distribution obtained using the Chronic Kidney Disease: Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) equations in a large primary care cohort, and to explore the implications of these classification differences for routine use in primary healthcare (PHC). Methods: A cross-sectional analysis was conducted using standardized electronic health records from 117,055 PHC patients in the Matosinhos Health Unit, Portugal, spanning 22 years (2000–2022). CKD staging followed KDIGO guidelines and focused on stages G3–G5, based on the most recent available serum creatinine value. CKD-EPI and MDRD equations were compared overall and across age strata, BMI categories, albuminuria categories (when available), and major comorbidity subgroups, including heart failure, diabetes, and hypertension. Results: Using CKD-EPI, a higher proportion of individuals were classified as CKD stages G3–G5 (9042; 7.73%) compared with MDRD (7686; 6.57%). Classification differences were most pronounced in advanced stages (relative increase with CKD-EPI: G3b +29.4%, G4 +23.6% and G5 +34.4%). Among individuals aged ≥80 years, equation-related classification differences were particularly marked in advanced stages (G5). Similarly, CKD-EPI was associated with higher CKD stage classification rates in high-risk subgroups, including patients with heart failure. Conclusions: Compared with MDRD, CKD-EPI yields a higher proportion of individuals classified into CKD stages, particularly advanced stages and among older adults and high-risk comorbidity subgroups. These findings highlight the substantial impact of equation choice on CKD stage classification in primary care and support the use of CKD-EPI for standardized eGFR reporting, while emphasizing that observed differences reflect classification rather than confirmed CKD diagnosis. Full article

The increasing global burden of chronic kidney disease (CKD) magnifies an urgent need to find treatable targets. Monocyte chemoattractant protein-1 (MCP-1/CCL2) is a chemokine secreted by kidney tubular epithelia in response to a variety of stimuli. To better understand the effects of tubular MCP-1 in response to kidney injury, we generated tubular epithelia-specific MCP-1 knockout mice (KO; Pax8-Mcp-1^fl/fl). We then exposed these mice and their control littermates to Adriamycin (Adr; 18 mg/kg, IV bolus). Thirty-two days after Adr injection, Mcp-1 transcript and protein levels were suppressed in the KO mice compared to their wild-type (WT) littermates. The KO mice exhibited no effect on survival, change in body weight, albuminuria, kidney function, glomerular or tubular injury, or tubulointerstitial fibrosis compared to WT. Overall, the results suggest that tubule-secreted MCP-1 is not necessary for progression of Adr-induced injury. These findings contribute to our understanding of the role of MCP-1 in kidney injury. Full article

Background: Ultrasound (US) imaging is widely used in Nephrology for the non-invasive assessment of renal morphology and perfusion. This study investigates correlations between sonographic parameters and renal function measured as estimated glomerular filtration rate (eGFR). Methods: This single-center prospective cross-sectional study enrolled 130 patients undergoing renal ultrasound. Parameters included renal length, parenchymal thickness, cortical–medullary differentiation, renal volume, and intrarenal resistive index (IR). eGFR was calculated using the CKD-EPI formula. Statistical analysis assessed correlations and developed a multivariable predictive model. Results: Renal length and parenchymal thickness correlated positively with eGFR (r = 0.381 and 0.364, p < 0.001), while IR correlated negatively (r = −0.549, p < 0.001). Multivariate regression identified sex, renal length, IR, cortical–medullary differentiation, and solitary/shrunken kidney as significant predictors of eGFR. The final model showed a predictive correlation coefficient of r = 0.6632. Specific ultrasound parameters, particularly renal length and IR, show significant correlation with eGFR. Conclusions: A predictive model incorporating these factors may assist in estimating renal function non-invasively. Full article

Background/Objectives: Patients with rheumatoid arthritis (RA) have an increased risk of chronic kidney disease (CKD) and cardiovascular disease, largely driven by persistent systemic inflammation. This study aimed to assess the risk of CKD in RA patients and to evaluate its association with structural joint damage and cardiovascular risk (CVR). Methods: In this cross-sectional study, 70 patients fulfilling the 2010 ACR/EULAR criteria for RA were evaluated. Structural joint damage was assessed using the Sharp/van der Heijde score (SHS). Renal involvement was evaluated by estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (ACR), and intrarenal resistive index (RRI). CVR was assessed using the SCORE system, adjusted according to EULAR recommendations, and carotid ultrasonography was performed to assess intima–media thickness (IMT) and atherosclerotic plaques. Results: SHS was significantly correlated with renal and vascular parameters, showing positive associations with ACR, RRI, and carotid IMT, and a negative correlation with eGFR (all p < 0.0001). CVR correlated positively with SHS, ACR, RRI, and IMT. Patients with elevated RRI (≥0.70) had longer disease duration, more severe joint damage, impaired renal function, and higher CVR. Conclusions: In RA patients, cumulative articular damage is closely associated with renal dysfunction and increased CVR, highlighting the central role of sustained inflammation in multiorgan involvement. Full article

Background/Objectives: Chronic kidney disease (CKD) affects almost 800 million people worldwide. Cardiovascular disease is the main cause of death in this population. Although physical activity is fundamental to systemic health, the evidence regarding its impact on the clinical outcomes of CKD populations is inconclusive. This protocol outlines the methodology for a systematic review and meta-analysis aimed at evaluating the association between physical activity and intensity and all-cause mortality, cardiovascular mortality, and cardiovascular disease. Methods: This protocol adheres to PRISMA-P and Cochrane Handbook guidelines and has been registered with PROSPERO (CRD420261302904). A systematic search will be conducted in MEDLINE, Scopus, Web of Science and the Cochrane Library until June 2026. Studies estimating the association between physical activity and all-cause mortality, cardiovascular mortality and cardiovascular disease in populations with CKD will be included. Two independent reviewers will perform study selection, data extraction and quality assessment using the Study Quality Assessment Tool from the United States National Institute of Health tool. The certainty of the evidence will be evaluated using the Grading of Recommendations, Assessment, Development and Evaluation tool. Narrative synthesis and random-effects meta-analysis will be conducted to calculate pooled effect estimates. Random-effects meta-analyses will be performed according to the level of physical activity, and meta-regressions will be used to control for the association with major covariates. Ethical approval is not required for this study. Results: The results will provide a comprehensive synthesis of the evidence regarding the use of physical activity as a non-pharmacological intervention to modify CKD progression. Conclusions: The findings will be disseminated through peer-reviewed journals and international conferences. Full article

Background: Both chronic kidney disease (CKD) and the haemodialysis procedure can contribute to disturbances in mineral homeostasis, which can potentially result in cellular pathologies. Our study aims to investigate trace element levels in haemodialysis patients and evaluate their potential impact on cellular adhesion molecules. This will clarify the clinical significance of trace element imbalances in this population. Methods: The study included 84 haemodialysis patients and 42 healthy controls. Trace element levels in blood (Zn, Cu, Mn, Mo, V, Sb and Cr) were measured using inductively coupled plasma mass spectrometry (ICP-MS), and cellular adhesion markers ICAM-1 and VCAM-1 were analysed by ELISA. Data analysis was conducted using SPSS 20.00, with significance set at p < 0.005. Results: Manganese (Mn) levels were significantly higher in haemodialysis patients (p = 0.019). Copper (Cu), Molybdenum (Mo), Vanadium (V), Antimony (Sb) and Chromium (Cr) levels were higher in the control group. Zinc (Zn) and Cr levels differed significantly between the control group (p = 0.018; p = 0.007). Cu levels were lower in hypertensive patients (p = 0.011), while Zn and Mn levels were higher in diabetic patients (p = 0.048 and p = 0.004, respectively). Dialysis duration, however, correlated with Sb (r = 0.295; p = 0.01), and Kt/V correlated with Mn, Sb and Cr (r = 0.256, r = 0.272 and r = 0.259, respectively; p = 0.05). Mo levels showed a positive correlation with both pre-dialysis (r = 0.230) and post-dialysis (r = 0.281) creatinine levels, and a negative correlation with post-dialysis GFR (r = −0.294). ICAM-1 and VCAM-1 levels were significantly elevated in dialysis patients (p = 0.001 for both); however, it was not found to be related to variables in the vascular access route. Conclusions: The levels of trace elements and adhesion molecules were examined in haemodialysis patients. High Mn levels indicate a risk of accumulation, while low Cu, Mo, V, Sb and Cr levels may require monitoring for deficiency. ICAM-1 and VCAM-1 levels in haemodialysis patients are associated with some trace elements (Mn and Zn); however, this relationship requires further evidence. In conclusion, the levels of trace elements and adhesion molecules in haemodialysis patients indicate the need for regular monitoring and show that the relationships between creatinine and GFR can be applied to larger patient groups. Full article

Vitamin D, a fat-soluble vitamin functioning as a hormone via the vitamin D receptor (VDR), is critical for calcium homeostasis and bone health. Vitamin D deficiency is linked to nutritional rickets, osteomalacia, and increased risk of non-communicable diseases such as cancer and diabetes. While serum 25(OH)D₃ is used to assess vitamin D status, its active form, 1α,25(OH)₂D₃, exerts context-dependent effects on calcium metabolism. Nonetheless, the therapeutic utility of native vitamin D is limited in certain pathologies. In chronic kidney disease (CKD), the renal conversion of 25(OH)D₃ to active 1α,25(OH)₂D₃ is compromised, necessitating the use of active synthetic analogs to bypass this metabolic defect. Furthermore, for dermatological and oncological disorders requiring supraphysiological dosing, synthetic analogs have been designed to dissociate beneficial anti-proliferative effects from the severe hypercalcemia induced by high-dose 1α,25(OH)₂D₃. VDR mediates transcriptional responses, modulated by co-regulators and chromatin remodeling complexes. Recent discoveries include non-genomic VDR pathways and SCAP (SREBP cleavage-activating protein)-dependent signaling that modulate lipid metabolism. Despite promising preclinical results, most synthetic VDR agonists fail to show efficacy in cancer therapy due to calcemic toxicity. However, compounds like eldecalcitol are effective in osteoporosis, especially in low-calcium-intake populations. Selective VDR modulators, akin to SERMs, exhibit tissue-specific effects. Moreover, novel VDR antagonists such as ZK168281 demonstrate potential to suppress hypercalcemia and vitamin D toxicity by inhibiting transcriptional activity and altering VDR localization. These agents may enable anti-inflammatory or anti-proliferative actions without calcemic risks. Understanding the nuanced biology of vitamin D and its analogs offers new avenues for therapeutic intervention beyond bone metabolism, including managing hyperparathyroidism, granulomatous diseases, and inflammation-associated disorders. Full article

Almost 10% of the global population suffers from chronic kidney disease (CKD). The inexistence of a therapeutic to restore renal function motivates the scientific community to search for new treatments. The 5/6 nephrectomy (Nx) rat model is widely used to mimic human CKD, but the impact of strain-specific responses on disease progression remains unclear. Here, we aimed to compare CKD development in Wistar, Lewis, and Fischer rats submitted to the Nx model. In summary, even submitted to the same surgical procedure, the three studied rat strains presented distinct patterns of CKD progression: Wistar rats exhibited faster and sustained renal function loss, with exuberant hypertension, proteinuria, and renal inflammation, being considered as excellent models to study rapidly progressive human nephropathy. Lewis animals, in turn, presented mild low-progressive CKD, which make this rat strain especially useful to simulate intermediate degrees of human CKD and to develop long-term tests. Finally, Fischer rats submitted to Nx did not even develop hypertension, proteinuria, or glomerular damage within 30 days. Moreover, compared to Wistar rats, both Lewis and Fischer animals have a relatively higher basal number of nephrons and a lower number of whole blood leukocytes, which may have contributed to the renoprotection exhibited by these rat strains. Full article

Recent advances in chiral analytical chemistry have revealed that fermented and natural foods contain substantial amounts of D-amino acids (D-AAs), the mirror-image counterparts of L-amino acids, leading to their recognition as nutraceutical components with potential health relevance. Although clinical evidence provides only limited support for their therapeutic efficacy, commercial expectations have outpaced scientific validation, and recent safety concerns emphasize the need for critical evaluation. In this review, we integrate findings from food chemistry, microbiology, biochemistry, physiology, and clinical research to provide a critical overview of dietary D-AAs. We examine how dietary exposure, microbial metabolism, host clearance capacity, and redox status collectively shape their context-dependent biological effects. We highlight the mechanistic linkage between D-amino acid oxidase (DAAO)-mediated hydrogen peroxide (H₂O₂) generation and organ-specific vulnerability, thereby clarifying the molecular basis of their “double-edged sword” actions. Within this interdisciplinary framework, we propose that D-AAs function as context-dependent “contronymic” molecules in cellular communication. By distinguishing physiological regulation, experimental modulation, and clinical application, this review aims to support evidence-based nutraceutical strategies and safety assessments that harness the potential benefits of D-AAs while minimizing associated risks. Full article

Globally, chronic kidney disease (CKD) affects over 800 million individuals and is characterized by significant genetic complexity. More than 600 genes are associated with hereditary kidney disease, which may manifest as isolated kidney issues or as part of a syndrome that also includes extrarenal manifestations. The aim of this study was to identify genetic variants in a group of ten patients who presented with clinical signs suggestive of genetic syndromes associated with CKD, or who were asymptomatic but had a positive family history of CKD. Extensive genetic testing (targeted gene panels and whole-exome sequencing—WES) identified a mutation in the PKD1 gene in 3 out of 10 cases. In one patient, a known mutation in the PKD2 gene was identified. Another four patients were diagnosed with Alport syndrome: three of these presented with de novo missense mutations in the COL4A5 gene, and one patient had a mutation in the COL4A3 gene. One patient was diagnosed with MODY5, caused by a known mutation in the HNF1B gene, and one patient was diagnosed with Bartter syndrome type 1, resulting from a known mutation in the SLC12A1 gene. We present genotype–phenotype correlations, highlighting the particularities of each patient within their family context. Our findings emphasize the importance of genotype–phenotype correlations in refining diagnosis, personalizing therapeutic management, and providing essential genetic counseling for at-risk relatives. Full article

Introduction: Uremic toxins have been shown to cause adverse pulmonary effects by inducing endothelial and epithelial dysfunction, disrupting the alveolar-capillary barrier, and increasing inflammation and oxidative stress. This article reviews these effects with a specific focus on chronic kidney disease and the mechanisms by which uremic toxins affect lung tissue. Methods: A narrative review was conducted using keywords related to uremic toxins and lung injury to search the PubMed database. An advanced literature review was conducted in PubMed to identify studies explaining the mechanisms underlying lung pathophysiology in chronic kidney disease (CKD), with particular focus on CKD-induced pulmonary epithelial and endothelial dysfunction. Additionally, to highlight the pathological processes of lung congestion in CKD, studies on CKD-induced dysfunction of the alveolar-capillary barrier were retrieved. Studies published up to November 2025 were evaluated. Results: A total of 148 articles were reviewed in full text. Uremic toxins negatively impact lung tissue structure and function through multiple mechanisms, including oxidative stress, inflammation, and direct effects. Uremic toxins appear to share signaling pathways in endothelial cells, including those linked to Mitogen-activated protein kinases (MAPK), the Aryl Hydrocarbon Receptor (AhR), the receptor for advanced glycation end products (RAGE), and pro-inflammatory transcription factors such as nuclear factor κB (NF-κB). Additionally, oxidative stress acts as a pro-inflammatory signal shared by several uremic toxins. The mechanisms behind the harmful interactions between CKD and lung disease are mostly unknown, although more evidence exists for acute kidney injury (AKI). Conclusions: Chronic kidney disease, which leads to the buildup of uremic toxins, negatively affects the lungs. Overall, the accumulation of uremic toxins in CKD impairs endothelial and epithelial cells and the alveolar capillary barrier. Further research is needed to understand the specific mechanisms underlying these effects and to identify therapeutic options to protect the lungs in these patients. Full article

Maladaptive tubular repair is a major contributor to fibrosis and chronic kidney disease (CKD), yet the molecular regulators of this process remain poorly understood. We report that the E3 ubiquitin ligases WWP1 and TRIM65 are novel regulators of tubular fibrosis. Both ligases were markedly induced in human and experimental CKD. WWP1 induction correlates with declining renal function in humans, highlighting the potential clinical relevance of WWP1. Profibrotic factor PAI-1 promotes a robust induction of WWP1 and TRIM65 in both primary human renal epithelial cells as well as cell line (HK-2). The silencing of WWP1 or TRIM65 significantly attenuated PAI-1-induced fibrotic signaling. Mechanistically, PAI-1 triggers a signaling cascade in which suppression of the regenerative BMP-7/SMAD5 pathway permits c-Myc induction, resulting in WWP1 and TRIM65 upregulation. The elevated expression of these ligases subsequently promotes epithelial dedifferentiation and fibrotic growth arrest. Restoration of BMP-7 or SMAD5 signaling disrupted this cascade and reduced fibrosis in renal tubular cells. Our study establishes a previously unrecognized PAI-1–c-Myc–WWP1/TRIM65 axis governing tubular maladaptive repair and positions WWP1 as a potentially new therapeutic target for slowing CKD progression. Full article

Ubiquitin-specific proteases (USPs) constitute the largest and most diverse family of deubiquitinating enzymes (DUBs), playing a pivotal role in maintaining protein homeostasis through reversible post-translational modifications (PTMs). Renal fibrosis represents the final common pathway of various chronic kidney diseases (CKDs), ultimately leading to irreversible nephron loss and end-stage renal disease (ESRD). With CKD affecting over 10% of the global adult population, fibrosis imposes a substantial clinical and economic burden. Despite this, effective antifibrotic therapies remain clinically elusive. Emerging evidence highlights the critical involvement of USPs in the pathogenesis of renal fibrosis through the potentiation of pro-fibrotic signaling pathways, inflammation, oxidative stress, cell cycle arrest and cellular senescence, as well as some other pathways. This review comprehensively summarizes the current understanding of USPs in renal fibrosis, detailing their structural characteristics, molecular mechanisms, and specific regulatory roles. Furthermore, we discuss recent advances in developing small-molecule USP inhibitors, providing novel insights into targeting the ubiquitin–proteasome system as a promising therapeutic strategy for combating renal fibrosis. Full article

Background: Chronic kidney disease (CKD) continues to place immense strain on health systems globally, with nurses at the centre of care delivery physically, emotionally, and relationally. In dialysis units, nurses form long-term therapeutic relationships with patients who depend on life-sustaining treatment several times a week. Objective: This study explored the lived experiences of professional nurses caring for patients with CKD in a dialysis unit, using Watson’s Theory of Human Caring as a guiding framework. Methods: A qualitative, exploratory, descriptive design was employed. Data were collected through in-depth face-to-face interviews with twelve professional nurses and analyzed using thematic analysis. Trustworthiness was ensured through credibility, dependability, confirmability, transferability, and authenticity. Ethical approval and informed consent were obtained. Results: Three themes emerged: (1) emotional and professional experiences, (2) systemic resource constraints, and (3) recommendations for practice improvement. These findings highlight the tension between caring ideals and systemic limitations. Conclusions: The study concludes that dialysis nursing is profoundly meaningful yet emotionally demanding. Strengthened emotional support, improved leadership visibility, consistent resource allocation, and enhanced nephrology nursing education are critical to sustaining compassionate care. The findings offer important insights for policy, workforce development, and quality improvement efforts in CKD care. Full article