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Search Results (298)

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Keywords = renal recovery

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17 pages, 1005 KiB  
Case Report
Management of Acute Kidney Injury Using Peritoneal Dialysis in a Bottlenose Dolphin (Tursiops truncatus) with Bilateral Ureteral Obstruction
by Todd L. Schmitt, Thomas H. Reidarson, James F. McBain, Hendrik H. Nollens, Amber P. Sanchez and David M. Ward
J. Zool. Bot. Gard. 2025, 6(3), 40; https://doi.org/10.3390/jzbg6030040 (registering DOI) - 7 Aug 2025
Abstract
An adult female bottlenose dolphin (Tursiops truncatus) housed at a public oceanarium presented with acute anorexia and lethargy. A blood analysis demonstrated mild leukocytosis, marked azotemia, hyperkalemia, and hyperphosphatemia suggestive of acute kidney injury or renal insufficiency. Ultrasound examination of the [...] Read more.
An adult female bottlenose dolphin (Tursiops truncatus) housed at a public oceanarium presented with acute anorexia and lethargy. A blood analysis demonstrated mild leukocytosis, marked azotemia, hyperkalemia, and hyperphosphatemia suggestive of acute kidney injury or renal insufficiency. Ultrasound examination of the dolphin revealed ascites, pleural effusion, bilateral nephrolithiasis, mild hydronephrosis, and bilateral hydroureter consistent with bilateral post-renal obstruction. Initial treatment consisted of antibiotics, oral fluids, and anti-inflammatory treatment. Further imaging diagnosed bilateral obstructing ureteroliths at both ureteral orifice junctions of the urinary bladder. The dolphin’s azotemia and hyperkalemia were nonresponsive to traditional medical management; therefore, peritoneal dialysis was performed for emergent clinical stabilization. Peritoneal dialysis was conducted over 3 days and facilitated the patient to undergo laser lithotripsy of the offending ureteral obstruction. The dolphin made a full recovery following months of intensive medical treatment for complications from peritoneal dialysis and secondary peritonitis. This is the first documented case of successful, though complicated, peritoneal dialysis in a cetacean. Full article
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19 pages, 2363 KiB  
Article
Can Biomarkers Predict Kidney Function Recovery and Mortality in Patients with Critical COVID-19 and Acute Kidney Injury?
by Noemí Del Toro-Cisneros, José C. Páez-Franco, Miguel A. Martínez-Rojas, Isaac González-Soria, Juan Antonio Ortega-Trejo, Hilda Sánchez-Vidal, Norma A. Bobadilla, Alfredo Ulloa-Aguirre and Olynka Vega-Vega
Diagnostics 2025, 15(15), 1960; https://doi.org/10.3390/diagnostics15151960 - 5 Aug 2025
Viewed by 139
Abstract
Background/Objectives: COVID-19 is a systemic viral infection that may lead to serious complications including acute kidney injury that requires kidney replacement therapy. The primary aim of this study was to evaluate urinary SerpinA3 (uSerpinA3) excretion as a biomarker of kidney recovery at [...] Read more.
Background/Objectives: COVID-19 is a systemic viral infection that may lead to serious complications including acute kidney injury that requires kidney replacement therapy. The primary aim of this study was to evaluate urinary SerpinA3 (uSerpinA3) excretion as a biomarker of kidney recovery at 90 days, and the mortality in patients with critical COVID-19 and AKI requiring kidney replacement therapy (KRT). Methods: The study included patients with critical COVID-19 on invasive mechanical ventilation (IMV) requiring KRT. Blood and urine samples were obtained when KRT was initiated (day zero), and thereafter on days 1, 3, 7, and 14 post-replacement. uSerpinA3, kidney injury molecule-1 (uKIM-1), and neutrophil gelatinase-associated lipocalin (uNGAL) were measured in urine, and interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-α) in peripheral blood. In addition, metabolomics in sample days zero and 3, and in the survivors on sample day 90 was performed by employing gas chromatography coupled with mass spectrometry. Results: A total of 60 patients were recruited, of whom 29 (48%) survived hospitalization and recovered kidney function by day 90. In the survivors, 79% presented complete recovery (CRR) and the remaining (21%) recovered partially (PRR). In terms of uSerpinA3, levels on days 7 and 14 predicted CRR, with AUC values of 0.68 (p = 0.041) and 0.71 (p = 0.030), respectively, as well as mortality, with AUC values of 0.75 (p = 0.007) and 0.76 (p = 0.015), respectively. Among the other biomarkers, the excretion of uKIM-1 on day zero of KRT had a superior performance as a CRR predictor [(AUC, 0.71 (p = 0.017)], and as a mortality predictor [AUC, 0.68 (p = 0.028)]. In the metabolomics analysis, we identified four distinct profiles; the metabolite that maintained statistical significance in predicting mortality was p-cresol glucuronide. Conclusions: This study strongly suggests that uSerpinA3 and uKIM-1 can predict CRR and mortality in patients with critical COVID-19 and AKI requiring KRT. Metabolic analysis appears promising for identifying affected pathways and their clinical impact in this population. Full article
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13 pages, 2697 KiB  
Communication
Oxidation-Active Radical TTM-DMODPA for Catalysis-Free Hydrogen Peroxide Colorimetric Sensing
by Qingmei Zhong, Xiaomei Rong, Tingting Wu and Chuan Yan
Biosensors 2025, 15(8), 490; https://doi.org/10.3390/bios15080490 - 29 Jul 2025
Viewed by 326
Abstract
As a crucial reactive oxygen species, hydrogen peroxide (H2O2) serves as both a physiological regulator and a pathological indicator in human systems. Its urinary concentration has emerged as a valuable biomarker for assessing metabolic disorders and renal function. While [...] Read more.
As a crucial reactive oxygen species, hydrogen peroxide (H2O2) serves as both a physiological regulator and a pathological indicator in human systems. Its urinary concentration has emerged as a valuable biomarker for assessing metabolic disorders and renal function. While conventional colorimetric determination methods predominantly employ enzymatic or nanozyme catalysts, we present an innovative non-catalytic approach utilizing the redox-responsive properties of organic neutral radicals. Specifically, we designed and synthesized a novel radical TTM-DMODPA based on the tris (2,4,6-trichlorophenyl) methyl (TTM) scaffold, which exhibits remarkable optical tunability and oxidative sensitivity. This system enables dual-mode H2O2 quantification: (1) UV-vis spectrophotometry (linear range: 2.5–250 μmol/L, LOD: 1.275 μmol/L) and (2) smartphone-based visual analysis (linear range: 2.5–250 μmol/L, LOD: 3.633 μmol/L), the latter being particularly suitable for point-of-care testing. Validation studies using urine samples demonstrated excellent recovery rates (96–104%), confirming the method’s reliability for real-sample applications. Our work establishes a portable, instrument-free platform for urinary H2O2 determination, with significant potential in clinical diagnostics and environmental monitoring. Full article
(This article belongs to the Section Optical and Photonic Biosensors)
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14 pages, 1664 KiB  
Article
Depletion of IGFALS Serum Level up to 3 Months After Cardiac Surgery, with Exploration of Potential Relationships to Surrogates of Organ Failures and Clinical Outcomes
by Krzysztof Laudanski, Mohamed A. Mahmoud, Hossam Gad and Daniel A. Diedrich
Curr. Issues Mol. Biol. 2025, 47(8), 581; https://doi.org/10.3390/cimb47080581 - 23 Jul 2025
Viewed by 250
Abstract
The insulin-like growth factor binding protein, acid-labile subunit (IGFALS), plays a crucial role in glucose metabolism and immune regulation, key processes in recovery from surgery. Here, we studied the perioperative serum IGFALS dynamics and explored potential clinical implications. A total of 79 patients [...] Read more.
The insulin-like growth factor binding protein, acid-labile subunit (IGFALS), plays a crucial role in glucose metabolism and immune regulation, key processes in recovery from surgery. Here, we studied the perioperative serum IGFALS dynamics and explored potential clinical implications. A total of 79 patients undergoing elective cardiac surgery with implementation of cardiopulmonary bypass had their serum isolated at baseline, 24 h, seven days, and three months postoperatively to assess serum concentrations of IGFALS and insulin growth factor 1 (IGF-1). Markers of perioperative injury included troponin I (TnI), high-mobility group box 1 (HMGB-1), and heat shock protein 60 (Hsp-60). Inflammatory status was assessed via interleukin-6 (IL-6) and interleukin-8 (IL-8). Additionally, we measured in vitro cytokine production to viral stimulation of whole blood and monocytes. Surrogates of neuronal distress included neurofilament light chain (NF-L), total tau (τ), phosphorylated tau at threonine 181 (τp181), and amyloid β40 and β42. Renal impairment was defined by RIFLE criteria. Cardiac dysfunction was denoted by serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Serum IGFALS levels declined significantly after surgery and remained depressed even at 3 months. Administration of acetaminophen and acetylsalicylic acid differentiated IGFALS levels at the 24 h postoperatively. Serum IGFALS 24 h post-operatively correlated with production of cytokines by leukocytes after in vitro viral stimulation. Serum amyloid-β1-42 was significantly associated with IGFALS at baseline and 24 h post-surgery Patients discharged home had higher IGFALS levels at 28 days and 3 months than those discharged to healthcare facilities or who died. These findings suggest that IGFALS may serve as a prognostic biomarker for recovery trajectory and postoperative outcomes in cardiac surgery patients. Full article
(This article belongs to the Special Issue The Role of Neuroinflammation in Neurodegenerative Diseases)
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15 pages, 392 KiB  
Systematic Review
Functional Status in Elderly Kidney Transplant Recipients: A Systematic Review Evaluating Physical Function, Frailty, and Cognitive Impairment as Predictors of Post-Transplant Outcomes
by Hachem Araji, Yazan A. Al-Ajlouni, Jana Nusier, Walid Sange, Elie El-Charabaty and Suzanne El-Sayegh
Diseases 2025, 13(7), 229; https://doi.org/10.3390/diseases13070229 - 21 Jul 2025
Viewed by 337
Abstract
Background: The management of end-stage renal disease (ESRD) is undergoing a paradigm shift, with increasing emphasis on kidney transplantation as a preferred treatment modality for elderly patients (≥65 years), who constitute a substantial portion of new ESRD cases. Transplantation offers markedly superior survival [...] Read more.
Background: The management of end-stage renal disease (ESRD) is undergoing a paradigm shift, with increasing emphasis on kidney transplantation as a preferred treatment modality for elderly patients (≥65 years), who constitute a substantial portion of new ESRD cases. Transplantation offers markedly superior survival and quality of life (QoL) advantages compared to dialysis for this demographic. Nevertheless, key determinants such as frailty, physical functionality, and cognitive function have emerged as critical predictors of post-transplant success. Despite their relevance, standardized methodologies for evaluating these parameters in transplantation candidacy remain absent. This systematic review examines the influence of frailty, physical functionality, and cognitive function on outcomes in elderly kidney transplant recipients. Methods: Adhering to PRISMA guidelines, a rigorous literature search was conducted across PubMed, CINAHL, Embase, PsycINFO, and the Web of Science for studies published up to October 31, 2024. Relevant studies focused on elderly transplant candidates and examined correlations between frailty, physical functionality, or cognitive function and post-transplant outcomes. The Newcastle–Ottawa Scale was employed to evaluate studies quality. Results: Seven studies met the inclusion criteria. Five explored physical functionality, demonstrating that better pre-transplant physical performance predicts enhanced survival. Two studies addressed frailty, utilizing the Fried frailty phenotype, and linked frailty to elevated mortality and diminished QoL recovery. Notably, no studies explored cognitive function in elderly kidney transplant candidates or recipients and its association with post-transplant outcomes, exposing a salient gap in the literature. The included studies’ varied methodologies, reliance on single time-point assessments, and exclusive focus on kidney transplant recipients restrict both comparability among studies and the generalizability of findings to the broader end-stage renal disease (ESRD) population. Conclusions: These findings underscore the profound impact of physical functionality and frailty on transplant outcomes in the growing elderly kidney transplant population, illuminating the necessity for standardized assessment protocols and targeted pre-transplant interventions. The critical gap in cognitive function research underscores a vital direction for future investigation. This research received no external funding. This review is registered with PROSPERO under registration ID CRD42025645838. Full article
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16 pages, 1969 KiB  
Article
Thirteen-Year Sequelae of Marburg Virus Disease Survival: Persistent Cardiometabolic, Immunometabolic, and Haematological Alterations in the Absence of Psychological Morbidity
by Jennifer Serwanga, Raymond Ernest Kaweesa, Joseph Katende Ssebwana, Goeffrey Odoch, Raymond Reuel Wayesu, Anne Daphine Ntabadde, Deborah Mukisa, Peter Ejou, FiloStudy Team, Julius Julian Lutwama and Pontiano Kaleebu
Pathogens 2025, 14(7), 678; https://doi.org/10.3390/pathogens14070678 - 9 Jul 2025
Viewed by 442
Abstract
Background: Marburg virus disease (MVD) is a highly lethal filoviral infection, yet its long-term health consequences remain poorly understood. We present one of the most temporally distant evaluations of MVD survivors, conducted 13 years post-outbreak in Uganda, offering novel insights into chronic [...] Read more.
Background: Marburg virus disease (MVD) is a highly lethal filoviral infection, yet its long-term health consequences remain poorly understood. We present one of the most temporally distant evaluations of MVD survivors, conducted 13 years post-outbreak in Uganda, offering novel insights into chronic physiological, biochemical, haematological, and psychosocial outcomes. Methods: A cross-sectional, community-based study compared ten MVD survivors with nineteen age- and sex-matched unexposed controls. Clinical evaluations included vital signs, anthropometry, mental health screening, and symptom reporting. Laboratory analyses covered electrolytes, inflammatory markers, renal and liver function tests, haematology, and urinalysis. Standardised psychological assessments measured anxiety, depression, perceived stigma, and social support. Findings: Survivors exhibited an elevated body mass index (BMI), higher systolic and diastolic blood pressure, and lower respiratory rates compared to controls, indicating ongoing cardiometabolic and autonomic changes. These trends may reflect persistent cardiometabolic stress and potential alterations in autonomic regulation, warranting further investigation. Biochemically, survivors exhibited disruptions in serum chloride, bilirubin, and total protein levels, suggesting subclinical hepatic and renal stress. Haematological analysis revealed persistent reticulocytosis despite normal haemoglobin levels, indicating long-term erythropoietic modulation. Despite these physiological changes, survivors reported minimal psychological morbidity, sharply contrasting with the post-recovery profiles of other viral haemorrhagic fevers. Stigma was prevalent during the outbreak; however, strong family support alleviated long-term psychosocial distress. Interpretation: Thirteen years post-infection, MVD survivors demonstrate multisystem physiological perturbations without marked psychological sequelae. These findings challenge assumptions of universal post-viral trauma and highlight the necessity for tailored survivor care models. Future longitudinal studies should investigate the mechanistic pathways underlying cardiometabolic and haematological reprogramming to inform intervention strategies in resource-limited settings. Full article
(This article belongs to the Special Issue Marburg Virus)
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15 pages, 2598 KiB  
Case Report
Two Cases of Chronic Tubular Necrosis Presenting as Fanconi Syndrome Induced by Red Yeast Rice Choleste-Help
by Kanako Mita, Shunsuke Takahashi, Satoshi Yanagida, Akihiro Aoyama, Takayuki Shiraishi, Takayuki Hamada, Yumiko Nakamura, Mariko Sato, Kento Hirose, Ryo Yamamoto, Yuya Shioda, Kaori Takayanagi, Izumi Nagayama, Yuko Ono, Hajime Hasegawa and Akito Maeshima
Diagnostics 2025, 15(13), 1722; https://doi.org/10.3390/diagnostics15131722 - 6 Jul 2025
Viewed by 445
Abstract
Background and Clinical Significance: Although dietary supplements have often been deemed safe, some have been linked to drug-induced nephropathy due to their diverse ingredients. The aim of this report is to enhance clinical awareness of a novel and emerging cause of Fanconi syndrome [...] Read more.
Background and Clinical Significance: Although dietary supplements have often been deemed safe, some have been linked to drug-induced nephropathy due to their diverse ingredients. The aim of this report is to enhance clinical awareness of a novel and emerging cause of Fanconi syndrome due to red yeast rice supplements and to contribute new histopathological and clinical data. Case Presentation: We report two cases of renal dysfunction and Fanconi syndrome associated with the use of red yeast rice supplements. Both patients presented with renal impairment accompanied by elevated markers of tubular injury, hypouricemia, hypokalemia, and glucosuria, consistent with Fanconi syndrome. Following the discontinuation of the red yeast rice supplement and initiation of steroid therapy, Fanconi syndrome resolved, however, moderate renal dysfunction persisted. Urinary NGAL levels improved after treatment in both cases. KIM-1 normalized in one case but remained elevated in the other. Uromodulin recovery was complete in one case and partial in the other. Renal biopsy revealed mild tubulointerstitial nephritis, with notable shedding of proximal tubular epithelial cells. Immunohistochemical analysis demonstrated reduced expression of URAT-1, Na-K ATPase, and Na-Pi IIa in some tubules. Conclusions: These findings suggest that renal injury induced by red yeast rice supplements is mediated by direct proximal tubular necrosis caused by a harmful substance in the supplement, resulting in persistence of tubular dysfunction. Full article
(This article belongs to the Special Issue Kidney Disease: Biomarkers, Diagnosis, and Prognosis: 3rd Edition)
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18 pages, 989 KiB  
Review
Neurological Manifestations of Hemolytic Uremic Syndrome: A Comprehensive Review
by Una Tonkovic, Marko Bogicevic, Aarish Manzar, Nikola Andrejic, Aleksandar Sic, Marko Atanaskovic, Selena Gajić, Ana Bontić, Sara Helena Ksiazek, Ana Mijušković, Nikola M. Stojanović and Marko Baralić
Brain Sci. 2025, 15(7), 717; https://doi.org/10.3390/brainsci15070717 - 4 Jul 2025
Viewed by 725
Abstract
Hemolytic uremic syndrome (HUS), a thrombotic microangiopathy primarily affecting the kidneys, can also involve the central nervous system (CNS), often leading to significant morbidity and mortality. Neurologic manifestations are among the most severe extra-renal complications, particularly in children and during outbreaks of Shiga [...] Read more.
Hemolytic uremic syndrome (HUS), a thrombotic microangiopathy primarily affecting the kidneys, can also involve the central nervous system (CNS), often leading to significant morbidity and mortality. Neurologic manifestations are among the most severe extra-renal complications, particularly in children and during outbreaks of Shiga toxin-producing Escherichia coli (STEC)-associated HUS (typical (tHUS)). This review explores the clinical spectrum, pathophysiology, diagnostic workup, and age-specific outcomes of neurologic involvement in both typical (tHUS) and atypical (aHUS). Neurologic complications occur in up to 11% of pediatric and over 40% of adult STEC-HUS cases in outbreak settings. Presentations include seizures, encephalopathy, focal deficits, movement disorders, and posterior reversible encephalopathy syndrome (PRES). Magnetic resonance imaging (MRI) commonly reveals basal ganglia or parieto-occipital lesions, though subtle or delayed findings may occur. Laboratory workup typically confirms microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and kidney damage, with additional markers of inflammation or metabolic dysregulation. Eculizumab is the first-line treatment for aHUS with CNS involvement, while its utility in STEC-HUS remains uncertain. Although many children recover fully, those with early CNS involvement are at greater risk of developing epilepsy, cognitive delays, or fine motor deficits. Adults may experience lingering neurocognitive symptoms despite apparent clinical recovery. Differences in presentation and imaging findings between age groups emphasize the need for tailored diagnostic and therapeutic strategies. Comprehensive neurorehabilitation and long-term follow-up are crucial for identifying residual deficits. Continued research into predictive biomarkers, neuroprotective interventions, and standardized treatment protocols is needed for improving outcomes in HUS patients with neurological complications. Full article
(This article belongs to the Special Issue New Advances in Neuroimmunology and Neuroinflammation)
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14 pages, 316 KiB  
Article
Age-Specific Clinical and Laboratory Features and Renal Involvement in Children with MIS-C: A Single Tertiary Centre Experience from Vojvodina
by Borko Milanović, Vesna Stojanović, Gordana Vijatov-Ðurić, Marijana Savin, Andrea Ðuretić, Jelena Kesić, Nenad Barišić, Ognjen Ležakov, Ivana Vorgučin, Gordana Vilotijević-Dautović and Katarina Koprivšek
Medicina 2025, 61(7), 1142; https://doi.org/10.3390/medicina61071142 - 25 Jun 2025
Viewed by 303
Abstract
Backgrounds and Objectives: Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare but potentially severe complication of SARS-CoV-2 infection, with increasingly reported renal manifestations. Materials and Methods: The aim of this retrospective study was to compare clinical and laboratory characteristics across [...] Read more.
Backgrounds and Objectives: Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare but potentially severe complication of SARS-CoV-2 infection, with increasingly reported renal manifestations. Materials and Methods: The aim of this retrospective study was to compare clinical and laboratory characteristics across age categories, with special emphasis on renal function. We analysed data from 64 patients with MIS-C treated between July 2020 and December 2023. Results: In children under 3 years of age, there was a higher prevalence of leucocytosis, elevated platelet counts, and anaemia, along with a lower frequency of complications. The 3–6-year age group was characterized by the presence of rash, hypoalbuminemia, and elevated transaminases. The 7–12-year age group showed the highest rate of organ dysfunction. In adolescents (13–18 years), neurological symptoms, the highest BMI values, the greatest prevalence of comorbidities, leukopenia, lymphopenia, and elevated GGT levels were observed. The incidence of acute kidney injury (AKI) was 6.3% (n = 4/64). Following treatment, the majority of patients achieved full recovery (n = 61/64; 95.2%). Conclusions: There are pronounced age-related differences in the clinical presentation of MIS-C, with distinct immune and clinical patterns suggesting developmental influences on disease expression and outcomes. Older children showed a higher prevalence of comorbidities and organ dysfunction compared to younger patients. Notably, this study found a markedly lower incidence of acute kidney injury (6.3%) compared to previously reported rates (20–30%), indicating potential regional or age-related protective factors. These findings highlight the importance of age-specific evaluation in MIS-C and underscore the need for further multicentre research to refine therapeutic protocols. Full article
(This article belongs to the Section Epidemiology & Public Health)
16 pages, 5453 KiB  
Article
Quasipaa spinosa-Derived Parvalbumin Attenuates Exercise-Induced Fatigue via Calcium Homeostasis and Oxidative Stress Modulation in Exhaustively Trained Mice
by Kai Sang, Congfei Lu, Yangfan Zhang and Qi Chen
Nutrients 2025, 17(12), 2043; https://doi.org/10.3390/nu17122043 - 19 Jun 2025
Viewed by 502
Abstract
Background: Quasipaa spinosa crude extract (QSce), a natural source rich in proteins such as parvalbumin (PV), has been traditionally used to promote physical recovery. However, its mechanisms in mitigating exercise-induced fatigue remain unclear. Methods: Using a murine treadmill exhaustion model, we evaluated [...] Read more.
Background: Quasipaa spinosa crude extract (QSce), a natural source rich in proteins such as parvalbumin (PV), has been traditionally used to promote physical recovery. However, its mechanisms in mitigating exercise-induced fatigue remain unclear. Methods: Using a murine treadmill exhaustion model, we evaluated the effects of QS-derived Parvalbumin (QsPV) (30 and 150 mg/kg/day) on endurance capacity, oxidative stress, tissue injury, and muscle function. Indicators measured included time to exhaustion, intracellular calcium levels, antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px)], lipid peroxidation (malondialdehyde, MDA), injury markers [creatine kinase (CK), lactate dehydrogenase (LDH), cardiac troponin I (cTnI)], renal function (blood urea), and muscle force. Results: QsPV-150 significantly increased time to exhaustion by 34.6% compared to the exercise-only group (p < 0.01). It reduced MDA by 41.2% in skeletal muscle and increased SOD and GSH-Px levels by 35.4% and 28.1%, respectively. Serum CK, LDH, and cTnI were reduced by 39.5%, 31.7%, and 26.8%, respectively, indicating protection against muscle and cardiac injury. QsPV also decreased blood urea by 22.3% and improved renal histology, with reduced glomerular damage and tubular lesions. At the molecular level, QsPV restored calcium balance and downregulated calpain-1/2 and atrophy-related genes (MuRF-1, MAFbx-32). Muscle contractile force (GAS and SOL) improved by 12.2–20.3%. Conclusions: QsPV attenuates exercise-induced fatigue through multi-organ protection involving calcium buffering, oxidative stress reduction, and anti-atrophy effects. These findings support its potential as a natural recovery-enhancing supplement, pending further clinical and pharmacokinetic studies. Full article
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17 pages, 2124 KiB  
Article
Reduced mtDNA Copy Number Links to Vascular Calcification and Restores After Transplantation
by Angelina Schwarz, Abdul Rashid Qureshi, Leah Hernandez, Lars Wennberg, Annika Wernerson, Karolina Kublickiene, Paul G. Shiels, Roberta Filograna, Peter Stenvinkel and Anna Witasp
Cells 2025, 14(12), 917; https://doi.org/10.3390/cells14120917 - 18 Jun 2025
Viewed by 849
Abstract
Patients with chronic kidney disease (CKD) face an increased risk of early vascular aging, progressive vascular calcification, and premature death. With increasing age, mitochondrial function and mitochondrial DNA copy number (mtDNA-cn) decline. This has been identified as an independent predictor of frailty and [...] Read more.
Patients with chronic kidney disease (CKD) face an increased risk of early vascular aging, progressive vascular calcification, and premature death. With increasing age, mitochondrial function and mitochondrial DNA copy number (mtDNA-cn) decline. This has been identified as an independent predictor of frailty and mortality in cardiovascular diseases (CVDs) and cancer. However, the relationship between mtDNA-cn and vascular calcification in the context of a uremic milieu remains ambiguous. We hypothesize that a lower mtDNA-cn is associated with medial calcification, as both are linked to impaired vascular health and accelerated aging. mtDNA-cn was analyzed in 211 CKD5 patients undergoing renal transplantation (RTx) and 196 healthy controls using quantitative PCR (qPCR) for three mtDNA genes (mtND1, mtND4, and mtCOX1) and single-locus nuclear gene hemoglobin beta (HbB). In 32 patients, mtDNA-cn was also quantified one year after RTx. The association between mtDNA-cn and vascular calcification scores, circulatory cell-free (ccf) mtDNA in plasma, and the surrogate marker of biological aging (skin autofluorescence) and CVD risk was assessed. mtDNA-cn was significantly lower in CKD5 patients than in controls and correlated with biological age, vascular calcification, and CVD risk. One year after RTx there was a significant recovery of mtDNA-cn in male patients compared to baseline levels. mtDNA-cn and ccf-mtDNA were inversely correlated. This prospective study provides novel insights into the link between low mtDNA-cn and vascular aging. It demonstrates that RTx restores mtDNA levels and may improve oxidative phosphorylation capacity in CKD. Further investigation is warranted to evaluate mtDNA as a biologically relevant biomarker and a potential therapeutic target for early vascular aging in the uremic environment. Full article
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15 pages, 2569 KiB  
Article
Rebamipide Attenuates Lupus Nephritis by Enhancing Antioxidative Defense in Podocytes: Evidence from a Lupus-Prone Mouse Model
by Young-Suk Song, Youngjae Park, Da-Som Kim, Se Gwang Jang and Seung-Ki Kwok
Int. J. Mol. Sci. 2025, 26(12), 5809; https://doi.org/10.3390/ijms26125809 - 17 Jun 2025
Viewed by 605
Abstract
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease that affects various organs, including the kidneys. Despite recent advancements, effective treatment options for renal involvement in SLE remain limited. Rebamipide, originally developed as a gastroprotective agent, has been reported to exert immunomodulatory effects [...] Read more.
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease that affects various organs, including the kidneys. Despite recent advancements, effective treatment options for renal involvement in SLE remain limited. Rebamipide, originally developed as a gastroprotective agent, has been reported to exert immunomodulatory effects in rheumatic diseases. Here, we aimed to evaluate the therapeutic potential of rebamipide in SLE using an animal model and to elucidate its mechanisms of action. We administered rebamipide or vehicle control to lupus-prone MRL/lpr mice and evaluated its efficacy on lupus-like phenotypes, including renal manifestations and immune cell profiles. Additionally, we investigated potential therapeutic mechanisms through in vitro treatment of murine immune cells and podocytes with rebamipide. Oral administration of rebamipide in lupus-prone mice significantly reduced kidney size, weight, and histopathological inflammation. Among circulating immune cell subsets, only regulatory T cells were significantly increased by rebamipide. In vivo treatment with rebamipide enhanced the expression of podocyte structural proteins, such as Synaptopodin, in kidney tissues, accompanied by the recovery of antioxidative factors, including nuclear factor erythroid 2-related factor 2 (Nrf2). Similarly, in vitro treatment of murine immune cells and podocytes with rebamipide replicated its immunoregulatory and antioxidative effects. Rebamipide is proposed as a potential therapeutic candidate for managing renal involvement in SLE through its antioxidative effects on podocytes. Full article
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22 pages, 6379 KiB  
Article
Inorganic Arsenite [As (III)] Represses Human Renal Progenitor Cell Characteristics and Induces Neoplastic-like Transformation
by Md Ehsanul Haque, Swojani Shrestha, Donald A. Sens and Scott H. Garrett
Cells 2025, 14(12), 877; https://doi.org/10.3390/cells14120877 - 10 Jun 2025
Viewed by 625
Abstract
Arsenic, in the form of inorganic arsenite, is toxic to the kidney and can cause acute kidney injury, manifesting as destruction of proximal tubule cells. Nephron repair is possible through the proliferation of resident tubular progenitor cells expressing CD133 and CD24 surface markers. [...] Read more.
Arsenic, in the form of inorganic arsenite, is toxic to the kidney and can cause acute kidney injury, manifesting as destruction of proximal tubule cells. Nephron repair is possible through the proliferation of resident tubular progenitor cells expressing CD133 and CD24 surface markers. We simulated regenerative repair in the continued presence of i-As (III) using a cell culture model of a renal progenitor cell line expressing CD133 (PROM1) and CD24. Continued exposure and subculturing of progenitor cells to i-As (III) led to a reduction in the expression of PROM1 and CD24, as well as a decrease in the ability to differentiate into tubule-like structures. Cessation of i-As (III) and recovery for up to three passages resulted in continued repression of PROM1 and reduced ability to differentiate. Chronically exposed cells exhibited an ability to form colonies in soft agar, suggesting neoplastic transformation. Chronically exposed cells also exhibited an induction of CD44, a cell surface marker commonly found in renal cell carcinoma, as well as in tubular repair in chronic renal injury such as chronic kidney disease. These results demonstrate potential adverse outcomes of renal progenitor cells chronically exposed to a nephrotoxicant, as well as in environmental exposure to arsenic. Full article
(This article belongs to the Special Issue Cellular and Molecular Basis in Chronic Kidney Disease)
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13 pages, 283 KiB  
Article
The Role of Ventricular Assist Devices in Patients with Ischemic vs. Non-Ischemic Cardiomyopathy
by Eglė Rumbinaitė, Dainius Karčiauskas, Grytė Ramantauskaitė, Dovydas Verikas, Gabrielė Žūkaitė, Liucija Rancaitė, Barbora Jociutė, Gintarė Šakalytė and Remigijus Žaliūnas
J. Pers. Med. 2025, 15(6), 241; https://doi.org/10.3390/jpm15060241 - 10 Jun 2025
Viewed by 890
Abstract
Background: The HeartMate 3 (HM3) left ventricular assist device (LVAD) has demonstrated improved clinical outcomes in patients with advanced heart failure (HF). However, the influence of underlying HF etiology—ischemic cardiomyopathy (ICM) versus dilated cardiomyopathy (DCM)—on post-implantation outcomes remains insufficiently characterized. Objectives: This [...] Read more.
Background: The HeartMate 3 (HM3) left ventricular assist device (LVAD) has demonstrated improved clinical outcomes in patients with advanced heart failure (HF). However, the influence of underlying HF etiology—ischemic cardiomyopathy (ICM) versus dilated cardiomyopathy (DCM)—on post-implantation outcomes remains insufficiently characterized. Objectives: This paper aims to evaluate early postoperative outcomes following HM3 LVAD implantation in patients with ICM versus DCM and to identify the preoperative hemodynamic and clinical predictors of early mortality and hemodynamic instability. Methods: We conducted a retrospective single-center cohort study of 30 patients who underwent HM3 LVAD implantation between 2017 and 2024. Patients were stratified by HF etiology (ICM, n = 17; DCM, n = 13), and preoperative clinical, echocardiographic, and right heart catheterization data were analyzed. The primary endpoint was 30-day postoperative survival. Secondary endpoints included postoperative hemodynamic stability and the need for vasopressor support. Results: Non-survivors (n = 13) demonstrated elevated central venous pressure (>16.5 mmHg), mean right ventricular pressure (>31.5 mmHg), and pulmonary vascular resistance (>7.5 Wood units), in addition to higher preoperative creatinine levels and longer cardiopulmonary bypass times. Vasopressor requirement postoperatively was associated with elevated pre-implant systolic pulmonary artery pressure. Conclusions: Preoperative right-sided pressures and renal dysfunction are strong predictors of early mortality following HM3 LVAD implantation. Patients with ICM exhibit greater early left ventricular recovery compared to those with DCM. These findings underscore the importance of comprehensive and personalized preoperative risk stratification—particularly in patients with DCM and pulmonary hypertension—to optimize postoperative outcomes and guide patient selection for durable LVAD support. Full article
(This article belongs to the Section Methodology, Drug and Device Discovery)
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Article
BRIGHT-HD—A Brazilian Research Investigation on Public Health Gains Comparing Survival Rates Between Hemodialysis and Hemodiafiltration: An Observational Study
by Eduardo P. Luciano, João Chang, Elaine C. S. Arantes, Aline Cordeiro, Sandra F. S. Reis, Douglas V. Andrade, Whelington F. Rocha, Andrea O. Magalhães, Cynthia M. Borges and Rosilene M. Elias
J. Clin. Med. 2025, 14(11), 3981; https://doi.org/10.3390/jcm14113981 - 5 Jun 2025
Viewed by 572
Abstract
Background/Objectives: High-flux online hemodiafiltration (OL-HDF) appears to be associated with better survival than hemodialysis (HD). In Brazil, OL-HDF is only affordable for patients with private health insurance. Although observational studies have shown a survival advantage with OL-HDF, even in Brazil, it is unclear [...] Read more.
Background/Objectives: High-flux online hemodiafiltration (OL-HDF) appears to be associated with better survival than hemodialysis (HD). In Brazil, OL-HDF is only affordable for patients with private health insurance. Although observational studies have shown a survival advantage with OL-HDF, even in Brazil, it is unclear whether this benefit applies to patients without private health insurance. We compared overall and cardiovascular mortality between OL-HDF and HD in patients treated exclusively through the public health care system. We hypothesized that patients on OL-HDF would have a higher survival rate than those on HD. Methods: This is an observational cohort study. Adult patients on maintenance hemodialysis or OL-HDF for at least one month during the period between 1 September 2022 and 1 December 2024 were enrolled into the study. The primary outcome was all-cause mortality. The secondary outcome was cardiovascular mortality. Fine-Gray sub-distribution hazard models were used to evaluate survival in the presence of competing events (kidney transplant and recovery of renal function). Results: Patients on HD (N = 321) and OL-HDF (N = 48) were similar in age, race, sex, and vascular access. Patients on HD were more likely to have diabetes (54.0% vs. 29.2%, p = 0.001) and spent more hours per week on dialysis (11.2 ± 1.8 vs. 10.5 ± 1.6 h, p = 0.006). In an adjusted Fine-Gray model, the hazard of death for patients on OL-HDF was 68% lower than that for patients on HD, and the risk of death for patients with an arteriovenous fistula was 55% lower compared to those with a catheter. Cardiovascular mortality did not differ between the groups. Conclusions: These findings suggest that OL-HDF is associated with an overall higher survival rate compared to HD, even for patients without private health insurance. Full article
(This article belongs to the Section Nephrology & Urology)
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