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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: Kidney cancer (RC) is a significant global health burden. Renal cell carcinoma (RCC) is the most common form of kidney cancer. Its predominant histological subtype is clear cell renal cell carcinoma (ccRCC), which is frequently diagnosed at an advanced local stage or with metastases. Detecting cancer at an early stage significantly increases the likelihood of a cure; therefore, research on new markers and a thorough understanding of tumor biology are essential. This study investigated the significance of aromatase (ARO), cathepsin S (CTSS), and matrix metalloproteinase 1 (MMP-1) as potential biomarkers in ccRCC. Methods: ARO, CTSS, and MMP-1 concentrations in plasma were determined using SPRi biosensors. Appropriate antibodies were used as biorecognition molecules in the biosensors. The samples analyzed came from 60 patients with histopathologically confirmed clear cell renal cell carcinoma (ccRCC) and from 26 patients diagnosed with chronic cystitis or benign prostatic hyperplasia (BPH). Results: A statistically significant increase (p < 0.00001) in the concentration of all proteins compared with the control samples was observed at the T3–T4 stage. The ARO concentration was already statistically significantly higher at the T1–T2 stage (p < 0.00001). The ROC curve for aromatase demonstrated high sensitivity and specificity for detecting ccRCC, with a cut-off point of 7.53 ng mL⁻¹. A moderate positive correlation was also found between the concentrations of the three tested substances in renal cancer, which may indicate potential interactions in the tumor’s pathogenesis. Conclusions: SPRI testing has been shown to be an alternative to standard methods for detecting potential ccRCC markers. The biosensors used in the study can simultaneously determine ARO, CTSS, and MMP-1. The results obtained suggest the potential importance of these proteins in the development of ccRCC, and our work proposes a new diagnostic technique that may aid in the diagnosis of ccRCC. 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

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

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: Chronic kidney disease (CKD) represents a state of persistent, sterile low-grade inflammation in which sustained innate immune activation accelerates renal decline and cardiovascular complications. Diet-induced gut dysbiosis and intestinal barrier dysfunction lower mucosal immune tolerance, promote metabolic endotoxemia, and position the gut as an upstream modulator of systemic inflammatory signaling along the gut–kidney axis. Scope: Most studies address microbiota-derived metabolites, food-derived bioactive peptides, or omega-3 fatty acids separately. This review integrates evidence across these domains and examines their convergent actions on epithelial barrier integrity, immune polarization, oxidative-inflammatory stress, and inflammasome-dependent pathways relevant to CKD progression. Key mechanisms: CKD-associated dysbiosis is characterized by reduced short-chain fatty acid (SCFA) production and increased generation and accumulation of uremic toxins and co-metabolites, including indoxyl sulfate, p-cresyl sulfate, trimethylamine N-oxide, and altered bile acids. Reduced SCFA availability weakens tight junction-dependent barrier function and regulatory immune programs, favoring Th17-skewed inflammation and endotoxin translocation. Bioactive peptides modulate inflammatory mediator networks and barrier-related pathways through effects on NF-κB/MAPK signaling and redox balance, while omega-3 fatty acids and specialized pro-resolving mediators support resolution-phase immune responses. Across these modalities, shared control points include barrier integrity, metabolic endotoxemia, oxidative stress, and NLRP3 inflammasome activation. Conclusions: Although evidence remains heterogeneous and largely preclinical, combined nutritional modulation targeting these convergent pathways may offer greater immunomodulatory benefit than isolated interventions. Future multi-omics-guided, factorial trials are required to define responder phenotypes and translate precision immunonutrition strategies into clinical CKD care. Full article

Primary hypoadrenocorticism (Addison’s disease) is an uncommon but potentially life-threatening endocrine disorder in dogs. Affected animals may present with clinicopathological features mimicking acute kidney injury (AKI). The challenge in diagnosing hypoadrenocorticism arises from its highly heterogeneous and non-specific clinical presentation, including acute kidney injury (AKI). This retrospective observational study aimed to evaluate dogs presenting with AKI and to identify cases in which primary hypoadrenocorticism was the underlying etiology. Thirty-four dogs diagnosed with acute kidney injury were evaluated at the Clinical Hospital for Companion Animals of the “Ion Ionescu de la Brad” University of Life Sciences, Iași, Romania, among which three (8.8%) were endocrinologically confirmed to have primary hypoadrenocorticism. The evaluation protocol included a complete clinical examination, hematological, biochemical, and hormonal investigations, urinalysis, abdominal ultrasonography, and an ACTH stimulation test. These dogs exhibited hyponatremia, hyperkalemia, a reduced sodium-to-potassium ratio, and azotemia at admission, closely resembling intrinsic AKI. Following fluid therapy and hormone replacement, rapid normalization of electrolyte and renal parameters was observed. These findings support hypovolemia and electrolyte imbalance as the primary mechanisms underlying reversible prerenal azotemia in these cases. If not diagnosed early, this condition has a significant risk of progressing to acute tubular necrosis. The findings highlight the need for careful differentiation between primary AKI and renal dysfunction secondary to Addison’s disease, as well as the importance of promptly initiating hormone replacement therapy. In conclusion, hypoadrenocorticism should be considered in dogs presenting with AKI and electrolyte imbalance. Early endocrine evaluation and prompt initiation of targeted therapy are essential to avoiding misdiagnosis and optimizing clinical outcomes. Full article

Background and Clinical Significance: Granulomatosis with polyangiitis (GPA) is an ANCA-associated vasculitis that often affects the respiratory tract and kidneys, while ocular involvement is less common and may delay diagnosis. Bilateral dacryoadenitis as an initial manifestation is particularly uncommon and can obscure early recognition. Case Presentation: A 24-year-old woman presented with recurrent epistaxis, headaches, and progressive bilateral eyelid swelling. MRI showed enlarged lacrimal glands consistent with granulomatous dacryoadenitis. Over the following weeks, she developed systemic symptoms and rapidly progressive renal impairment. Serology revealed positive c-ANCA and anti-PR3 antibodies, and HRCT demonstrated pulmonary nodules and ground-glass opacities. Renal biopsy confirmed necrotizing pauci-immune crescentic glomerulonephritis. Despite treatment with glucocorticoids, cyclophosphamide, and rituximab, renal recovery was incomplete, necessitating hemodialysis. Conclusions: This case illustrates bilateral dacryoadenitis as an early sign of GPA and emphasizes the need for prompt ANCA testing and renal evaluation. Early recognition is crucial to prevent irreversible kidney damage. Full article

Transient receptor potential canonical (TRPC) channels function as multimodal cation channels that integrate chemical and mechanical cues to regulate cellular signaling. Among them, TRPC3 and TRPC6 have been studied primarily in the context of cardiovascular and renal physiology, and their roles in other organ systems are now increasingly recognized. Although these channels are known to be activated downstream of phospholipase C (PLC) signaling, especially 1,2-diacylglycerol (DAG) production, their precise modes of activation under native physiological conditions remain incompletely understood. Recent structural and functional studies have greatly advanced our understanding of their primary activation by DAG. This review summarizes how decades of physiological analyses have revealed multiple modes of TRPC3 and TRPC6 channel activation beyond DAG gating, providing a broader perspective on their diverse regulatory mechanisms. This review also highlights recent progress in elucidating the channel properties, activation mechanisms, and the physiological as well as pathophysiological roles of TRPC3 and TRPC6 in cardiovascular contractility and remodeling, and discusses the remaining challenges that will lead to the establishment of TRPC3 and TRPC6 as validated therapeutic targets. Full article

Autoantibodies have long been regarded as passive reflections of immune dysregulation in connective tissue diseases (CTDs). Recent advances in systems immunology and molecular pathology have fundamentally redefined them as active molecular fingerprints that delineate distinct disease endophenotypes with predictive power for clinical trajectories and therapeutic responses. Rather than mere epiphenomena, autoantibodies encode precise information about dominant immune pathways, organ tropism, and pathogenic mechanisms. This review synthesizes emerging evidence that autoantibody repertoires—defined by specificity, structural properties, and functional characteristics—stratify patients beyond traditional clinical taxonomy into discrete pathobiological subsets. Specific signatures such as anti-MDA5 in rapidly progressive interstitial lung disease, anti-RNA polymerase III in scleroderma renal crisis, and anti-Ro52/TRIM21 in systemic overlap syndromes illustrate how serological profiles predict outcomes with remarkable precision. Mechanistically, autoantibody pathogenicity is modulated by immunoglobulin isotype distribution, Fc glycosylation patterns, and tissue-specific receptor expression—variables that determine whether an antibody functions as a biomarker or pathogenic effector. The structural heterogeneity of autoantibodies, shaped by cytokine microenvironments and B-cell subset imprinting, creates a dynamic continuum between pro-inflammatory and regulatory states. The integration of serological, transcriptomic, and imaging data establishes a precision medicine framework: autoantibodies function simultaneously as disease classifiers and therapeutic guides. This endophenotype-driven approach is already influencing trial design and patient stratification in systemic lupus erythematosus, systemic sclerosis, and inflammatory myopathies, and is reshaping both clinical practice and scientific taxonomy in CTDs. Recognizing autoantibodies as endophenotypic determinants aligns disease classification with pathogenic mechanism and supports the transition towards immunologically informed therapeutic strategies. Full article

Acute kidney injury (AKI) remains a major clinical challenge, with high morbidity and limited therapeutic options. In recent years, mitochondria have gained considerable attention as key regulators of the metabolic and immune responses during renal injury. Beyond their classical role in ATP production, mitochondria participate directly in inflammatory signaling, releasing mitochondrial DNA and other DAMPs that activate pathways such as TLR9, cGAS–STING, and the NLRP3 inflammasome. At the same time, immune cells recruited to the kidney undergo significant metabolic shifts that influence whether injury progresses or resolves. Increasing evidence also shows that immune-modulating therapies, including immune checkpoint inhibitors and innovative cell-based immunotherapies, can influence mitochondrial integrity, thereby altering renal susceptibility to injury. This review first summarizes the established knowledge on mitochondrial dysfunction in AKI, with emphasis on distinct mechanistic pathways activated by chemotherapy and immunotherapy. It then discusses emerging mitochondrial-targeted therapeutic strategies, logically integrating preclinical insights with data from ongoing and proposed clinical trials to present a coherent translational outlook. Full article

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder marked by progressive kidney enlargement and cyst formation, often resulting in end-stage renal disease (ESRD). Oxidative stress (OxS) significantly contributes to renal damage in chronic kidney disease (CKD) and ADPKD. While the Mediterranean diet (Med-diet) is known for its antioxidative and anti-inflammatory effects, its impact on OxS in ADPKD remains unclear. This study aimed to assess the relationship between adherence to the Med-diet, OxS levels, and renal function in ADPKD patients. We enrolled 63 ADPKD patients aged 18–70 years with CKD stages G2–G4. Adherence to the Med-diet was evaluated using the PREDIMED questionnaire. OxS markers (NOX2-derived peptide [sNOX2-dp] and hydrogen peroxide [H₂O₂]) were measured via ELISA. Correlations between these markers, Med-diet adherence, serum creatinine, and estimated glomerular filtration rate (eGFR) were analyzed. Higher adherence to the Med-diet was associated with significantly lower OxS markers (sNOX2, p < 0.001; H₂O₂, p = 0.04). Reduced NOX2 and H₂O₂ levels correlated with lower creatinine and higher eGFR (NOX2, p < 0.001; H₂O₂, p < 0.001), suggesting an inverse relationship between OxS and renal function. In conclusion, adherence to the Mediterranean diet appears to be associated with lower levels of oxidative stress and may slow the progression of chronic kidney disease. These findings suggest that dietary interventions could mitigate disease progression by modulating OxS. Further studies are needed to confirm these results and explore the long-term effects of the Med-diet on disease progression. Full article

Introduction: Radiotracer-based nuclear imaging, including positron emission tomography (PET) and single-photon emission computed tomography (SPECT), can complement conventional cross-sectional imaging in renal cell carcinoma (RCC) by providing biological characterisation of tumour metabolism, angiogenesis, hypoxia, and the tumour microenvironment. While computed tomography (CT) and magnetic resonance imaging (MRI) remain the diagnostic standard, accumulating evidence suggests that selected nuclear imaging techniques may offer incremental value in specific clinical scenarios. Methods: A narrative literature review was performed using PubMed, Embase, and Web of Science to identify preclinical, retrospective, and prospective studies evaluating PET and SPECT radiotracers in localised and metastatic RCC. Priority was given to meta-analyses, multicentre prospective trials, and studies with histopathological correlation. Results: [¹⁸F]fluorodeoxyglucose (FDG) PET/CT demonstrates limited sensitivity for primary renal tumours (pooled sensitivity of approximately 60%) but performs substantially better in metastatic and recurrent disease (pooled sensitivity and specificity of approximately 85–90%), where uptake correlates with tumour grade, progression-free survival, and overall survival. [^99mTc]sestamibi SPECT/CT differentiates oncocytoma and hybrid oncocytic/chromophobe tumours from malignant RCC with pooled sensitivity and specificity of around 85–90%, supporting its role in evaluating indeterminate renal masses rather than staging. Prostate-specific membrane antigen (PSMA) PET/CT shows high detection rates in clear-cell RCC, particularly in metastatic disease, with reported sensitivities of approximately 85–90% and management changes in up to 40–50% of selected cohorts. Carbonic anhydrase IX (CAIX)-targeted PET/CT enables the biologically specific visualisation of clear-cell RCC, achieving sensitivities and specificities in the range of 85–90% in prospective phase II and III trials for primary tumour characterisation. Fibroblast activation protein inhibitor (FAPI) PET/CT demonstrates high tumour-to-background uptake in early RCC studies, but evidence remains preliminary, with small cohorts and recognised non-specific uptake in benign inflammatory and fibrotic conditions. Conclusions: Radiotracer-based nuclear imaging provides complementary, biology-driven insights in RCC that extend beyond anatomical assessment. While most modalities remain adjunctive or investigational and are not recommended for routine use, selective application in carefully chosen clinical scenarios may enhance tumour characterisation, prognostication, and personalised treatment planning. Full article

Background and Clinical Significance: Cutaneous aspergillosis caused by Aspergillus flavus is rare and coinfection with Klebsiella pneumoniae was reported only in pulmonary disease. Case Presentation: We describe a 57-year-old woman with no prior comorbidities who developed septic shock requiring intensive care, broad-spectrum antibiotics, corticosteroids, and renal replacement therapy. Six days after discharge, she was readmitted with fever, leukopenia, thrombocytopenia, cavitary lung lesions, and multiple erythematous nodules on the limbs and mammary regions. Bronchial aspirate cultures detected K. pneumoniae, while progressive cutaneous lesions required surgical debridement. Histopathology revealed angioinvasive septate hyphae, and MALDI-TOF identified A. flavus. The K. pneumoniae strain was extensively drug resistant; A. flavus was susceptible only to azoles. Despite targeted therapy, lesions progressed requiring bilateral mastectomy. Conclusions: This case illustrates a previously unreported scenario in which secondary immunosuppression after severe sepsis led to concurrent cutaneous A. flavus infection and extensively drug-resistant (XDR) K. pneumoniae. Early recognition of mixed fungal–bacterial infections is essential for appropriate management. Full article

This article explores the multifaceted role of micro-ribonucleic acids (RNAs) (miRNAs) as critical posttranscriptional regulators in renal physiology and disease, with a focus on their emerging significance in glomerulopathies. miRNAs, small endogenous noncoding RNAs, modulate gene expression by promoting messenger RNA degradation or inhibiting translation, thereby orchestrating essential cellular processes such as proliferation, differentiation, apoptosis, and stress responses. Recent advances have revealed that aberrant miRNA expression profiles are intricately linked to the pathogenesis and progression of various renal diseases, including acute kidney injury, chronic kidney disease, alloimmune injury in solid organ transplantation and glomerulonephritis. This review summarizes the pathogenic and protective roles of miRNAs in major glomerulopathies, discusses their potential as diagnostic and prognostic biomarkers, and outlines future directions for their integration into personalized therapeutic strategies. At the moment, it is not fully established whether some of these mechanisms are the primary pathogenic driver or a secondary response. Combining miRNAs with other molecular markers may further enhance diagnostic and predictive accuracy, facilitating clinical translation, while selective targeting of specific miRNAs at different stages of disease progression could offer promising therapeutic opportunities. Full article