RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Ilex cornuta is a valuable species of the Holly genus (Aquifoliaceae), and mainly distributed in eastern China. It is not only made into tea, namely Kudingcha, but also used as traditional medicine to relieve cough, headache, gout, and nourish liver and kidney. AIM OF THE STUDY: The purpose of this study was to explore the exact efficacy of different extracts from Ilex cornuta in the treatment of hyperuricemia in vitro and in vivo, and to explore its pharmacological mechanism, so as to bring new ideas for the development of new drugs for reducing uric acid (UA) and anti-gout. MATERIALS AND METHODS: Five crude extracts from Ilex cornuta leaves were extracted by different methods. Then, the xanthine oxidase inhibitory activity and antioxidant capacity of 5 extracts in vitro were compared to screen the extract with the most UA regulating potential. In vivo experiment, hyperuricemia model of mice was established by intragastric administration of potassium oxonate and feeding high yeast diet. Biochemical indexes such as serum UA level, xanthine oxidase activity, liver and kidney index of mice in each group were detected. The pathological sections of kidney and liver tissues were also observed and compared. The mechanism of Ilex cornuta leaves (western blotting, and RT-qPCR) in the treatment of hyperuricemia was further explored by targeting UA transporters ABCG2, GLUT9, and URAT1. RESULTS: The in vitro results of inhibitory activity of xanthine oxidase showed that the crude saponin extract was the best, followed by crude flavonoids extract. Then, the in vivo results reflected that both crude saponins and crude flavonoids extracts could significantly reduce the serum UA level, inhibit the activity of xanthine oxidase in serum and liver, and maintain serum urea nitrogen and creatinine at normal level. Meanwhile, there was no liver and kidney injury in mice. Through the comparison of the mechanism results, it was found that both extracts could up-regulate the expression of ABCG2 protein and mRNA related to UA excretion, and down-regulate the expression of GLUT9 and URAT1 protein and mRNA. CONCLUSION: The crude flavonoids and saponins of Ilex cornuta leaves not only inhibited XOD activity in vitro, but also significantly controlled XOD activity and reduced UA level in hyperuricemia mice in vivo. One of the potential mechanisms was to regulate UA level in vivo by regulating ABCG2, GLUT9, and URAT1 transporters directly related to UA transport, thus achieving the effect of intervening hyperuricemia. This study provided a preliminary experimental basis for the development of new drugs of Ilex cornuta leaves for treating hyperuricemia.
Asunto(s)
Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Hiperuricemia , Ilex , Transportadores de Anión Orgánico , Extractos Vegetales , Hojas de la Planta , Ácido Úrico , Xantina Oxidasa , Animales , Hiperuricemia/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/química , Hojas de la Planta/química , Ácido Úrico/sangre , Xantina Oxidasa/metabolismo , Xantina Oxidasa/antagonistas & inhibidores , Transportadores de Anión Orgánico/metabolismo , Masculino , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Ilex/química , Ratones , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Hígado/efectos de los fármacos , Hígado/metabolismo , Proteínas Facilitadoras del Transporte de la Glucosa/metabolismo , Antioxidantes/farmacología , Antioxidantes/aislamiento & purificación , Modelos Animales de Enfermedad , Proteína 1 de Transporte de Anión OrgánicoRESUMEN
ETHNOPHARMACOLOGICAL PREVALENCE: Hyperglycemia in diabetes increases the generation of advanced glycation end products (AGEs) through non-enzymatic reactions. The interaction between AGEs and their receptors (RAGE) leads to oxidative and inflammatory stress, which plays a pivotal role in developing diabetic nephropathy. Syzygium cumini (SC) L. (DC.) homeopathic preparations viz. 200C, 30C, and mother tincture [MT] are used to treat diabetes. This study aimed to elucidate the regulatory effects of SC preparations (200C, 30C, and MT) on the nuclear factor erythroid 2-related factor 2 (Nrf2) - nuclear factor-κB (NF-κB) pathways and mitochondrial dysfunction in mitigating diabetic nephropathy (DN). MATERIALS AND METHODS: Streptozotocin-induced diabetic rats were treated with SC preparations (200C, 30C, MT; 1:20 dilution in distilled water; 600 µL/kg body weight) and metformin (45 mg/kg body weight) twice daily for 40 days. DN was evaluated through biochemical parameters and histological examination. Renal tissue lysates were analyzed for glycation markers. Protein and gene levels of Nrf2, NF-κB, and mitochondrial dysfunctional signaling were determined via western blotting and RT-qPCR. An immunohistochemical analysis of the kidneys was performed. In vitro, human serum albumin (HSA - 10 mg/ml) was glycated with methylglyoxal (MGO - 55 mM) in the presence of SC preparations (200C, 30C, MT) for eight days. Glycated samples (400 µg/mL) were incubated with renal cells (HEK-293) for 24 h. Further reactive oxygen species production, Nrf2 nuclear translocation, and protein or gene expression of Nrf2 and apoptosis markers were analyzed by western blotting, RT-qPCR, and flow cytometry. Molecular docking of gallic and ellagic acid with the HSA-MGO complex was performed. RESULT: In vivo experiments using streptozotocin-induced diabetic rats treated with SC preparations exhibited improved biochemical parameters, preserved kidney function, and reduced glycation adduct formation in a dose-dependent manner. Furthermore, SC preparations downregulated inflammatory mediators such as RAGE, NF-κB, vascular endothelial growth factor (VEGF), and Tumor necrosis factor α (TNF-α) while upregulating the Nrf2-dependent antioxidant and detoxification pathways. They downregulated B-cell lymphoma 2 (Bcl-2) associated X-protein (BAX), C/EBP homologous protein (CHOP), Dynamin-related protein 1 (DRP1), and upregulated BCL 2 gene expression. Notably, SC preparations facilitated nuclear translocation of Nrf2, leading to the upregulation of antioxidant enzymes and the downregulation of oxidative stress markers. Molecular docking studies revealed favorable interactions between gallic (-5.26 kcal/mol) and ellagic acid (-4.71 kcal/mol) with the HSA-MGO complex. CONCLUSION: SC preparations mitigate renal cell apoptosis and mitochondrial dysfunction through Nrf2-dependent mechanisms.
Asunto(s)
Diabetes Mellitus Experimental , Nefropatías Diabéticas , Factor 2 Relacionado con NF-E2 , Syzygium , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/metabolismo , Syzygium/química , Humanos , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Masculino , Ratas , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , FN-kappa B/metabolismo , Extractos Vegetales/farmacología , Transducción de Señal/efectos de los fármacos , Células HEK293 , Estrés Oxidativo/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Productos Finales de Glicación Avanzada/metabolismo , Estreptozocina , Ratas Wistar , Antioxidantes/farmacología , Ratas Sprague-DawleyRESUMEN
Introduction. Renal functional reserve (RFR) is the kidney capability of increasing its basal glomerular filtration rate (GFR) at least 20% after an adequate stimulus. Renal disorders have been reported in seropositive HIV patients, particularly the decrease in glomerular filtration rate (eGFR), nephrotic syndrome, and proximal tubular deficiency associated with the disease itself or the use of some anti-retroviral treatments. Thus, it was decided to carry out a prospective study in order to evaluate if RFR test was preserved in naive HIV patients. Material and Method. GFR was measured by using cimetidine-aided creatinine clearance (CACC), and RFR as described Hellerstein et al. in seropositive naive HIV patients and healthy volunteers. Results. RFR was evaluated in 12 naïve HIV patients who showed positive RFR (24.8±2%), but significantly lower compared to RFR in 9 control individuals (90.3 ± 5%). Conclusion. In this study was found that renal functional reserve was positive in naïve HIV patients, but significantly lower compared to renal functional reserve achieved by seronegative healthy individuals.
Asunto(s)
Tasa de Filtración Glomerular , Infecciones por VIH , Humanos , Estudios Prospectivos , Masculino , Adulto , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Infecciones por VIH/fisiopatología , Femenino , Persona de Mediana Edad , Riñón/fisiopatología , Creatinina/sangre , Cimetidina/uso terapéuticoRESUMEN
BACKGROUNDS: Progranulin (PGRN) is a growth factor-like molecule with diverse roles in homeostatic and pathogenic processes including the control of immune and inflammatory responses. Pathogenic inflammation is a hallmark of systemic lupus erythematosus (SLE) and elevated serum levels of PGRN has been evaluated as a biomarker of disease activity in SLE. However, the role of PGRN in SLE has not been fully investigated. This study is aimed to determine the potential involvements of PGRN in SLE. METHODS: Wild type (WT) and PGRN knockout (PGRN-/-) C57BL/6 mice received intraperitoneal injection of pristane for induction of a murine model of SLE. Sera were collected every biweekly and levels of anti-dsDNA antibody, IgG, and inflammatory factors were measured. Mice were sacrificed 5 months later and the renal lesions, as well as the proportions of T cell subtypes in the spleen were analyzed. RESULTS: Following exposure to pristane, PGRN-/- mice generated significantly lower levels of anti-dsDNA antibody and IgG relative to WT mice. PGRN-/- mouse kidneys had less IgG and collagen deposition compared with WT mice after pristane injection. CONCLUSION: The results indicate that PGRN participates in inflammatory response and renal damage in pristane induced SLE models, suggesting that PGRN mediates the onset of SLE.
Asunto(s)
Anticuerpos Antinucleares , Modelos Animales de Enfermedad , Inmunoglobulina G , Péptidos y Proteínas de Señalización Intercelular , Lupus Eritematoso Sistémico , Ratones Endogámicos C57BL , Ratones Noqueados , Progranulinas , Terpenos , Animales , Lupus Eritematoso Sistémico/inmunología , Ratones , Inmunoglobulina G/sangre , Anticuerpos Antinucleares/sangre , Riñón/metabolismo , Riñón/inmunología , Bazo/inmunología , Bazo/metabolismo , ColágenoRESUMEN
We investigated the potential correlation between miR-223 and NAcHT, LRR, and PYd domain-containing protein 3 (NLRP3) in the context of renal ischemia-reperfusion injury (RIRI), which is a leading cause of acute renal failure with significant mortality rates. Additionally, miR-223 has been implicated in renal inflammation, further highlighting its relevance to this study. C57BL/6 male mice were used as RIRI models. After successful modeling, pathological examinations and serum creatinine and miR-223 levels were tested. Pro-inflammatory cytokine (IL-1ß, IL-6, IL-8, NLPR3, TLR4) expression was detected in mice by western blot (kidney tissue) and enzyme-linked immunosorbent assay (serum). HK-2 cells were used for in vitro experiments. A hypoxia/reoxygenation (H/R) model was used, and miR-223 and pro-inflammatory cytokine levels were detected using PCR and western blot assays, respectively. A dual-luciferase reporter assay was conducted to confirm the binding of miR-223 to NLPR3. Next, NLRP3 was knocked down to determine whether the anti-inflammatory function of miR-223 is dependent on NLRP3. MiR-223 expression was lower in RIRI mice than in the sham operation group. The level of miR-223 negatively correlated with serum creatinine levels and the severity of tubule injury. Increased proinflammatory cytokine levels in RIRI mice were observed. In vitro, miR-223 alleviated the inflammatory response in H/R treated cells by inhibiting proinflammatory cytokines. Dual-luciferase reporter and western blot assays confirmed the binding of miR-223 to NLRP3. NLRP3 knockdown reversed the anti-inflammatory effects of miR-223 in HK-2 cells. MiR-223 plays an anti-inflammatory role in RIRI by targeting NLRP3 to repress pro-inflammatory factors.
Asunto(s)
Riñón , Ratones Endogámicos C57BL , MicroARNs , Proteína con Dominio Pirina 3 de la Familia NLR , Daño por Reperfusión , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Animales , MicroARNs/genética , MicroARNs/metabolismo , Daño por Reperfusión/metabolismo , Daño por Reperfusión/genética , Daño por Reperfusión/patología , Masculino , Riñón/metabolismo , Riñón/patología , Humanos , Ratones , Inflamación/metabolismo , Inflamación/patología , Inflamación/genética , Línea Celular , Citocinas/metabolismoRESUMEN
In the present study, we investigated whether curcumin administration would interfere with the main renal features of l-NAME-induced hypertension model. For this purpose, we conducted both in vitro and in vivo experiments to evaluate renal indicators of inflammation, oxidative stress, and metalloproteinases (MMPs) expression/activity. Hypertension was induced by l-NAME (70 mg/kg/day), and Wistar rats from both control and hypertensive groups were treated with curcumin (50 or 100 mg/kg/day; gavage) or vehicle for 14 days. Blood and kidneys were collected to determine serum creatinine levels, histological alterations, oxidative stress, MMPs expression and activity, and ED1 expression. l-NAME increased blood pressure, but both doses of curcumin treatment reduced these values. l-NAME treatment increased creatinine levels, glomeruli area, Bowman's space, kidney MMP-2 activity, as well as MMP-9 and ED1 expression, and reduced the number of glomeruli. Curcumin treatment prevented the increase in creatinine levels, MMP-2 activity, and reduced MMP-2, MMP-9, ED1, and superoxide levels, as well as increased superoxide dismutase activity and partially prevented glomeruli alterations. Moreover, curcumin directly inhibited MMP-2 activity in vitro. Thus, our main findings demonstrate that curcumin reduced l-NAME-induced hypertension and renal glomerular alterations, inhibited MMP-2 and MMP-9 expression/activity, and reduced oxidative stress and inflammatory processes, which may indirectly impact hypertension-induced renal outcomes.
Asunto(s)
Curcumina , Hipertensión , Metaloproteinasa 2 de la Matriz , Metaloproteinasa 9 de la Matriz , NG-Nitroarginina Metil Éster , Ratas Wistar , Animales , Curcumina/farmacología , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , NG-Nitroarginina Metil Éster/farmacología , Hipertensión/inducido químicamente , Hipertensión/tratamiento farmacológico , Hipertensión/metabolismo , Ratas , Masculino , Riñón/efectos de los fármacos , Riñón/patología , Riñón/metabolismo , Estrés Oxidativo/efectos de los fármacos , Enfermedades Renales/inducido químicamente , Enfermedades Renales/prevención & control , Enfermedades Renales/patología , Enfermedades Renales/metabolismo , Enfermedades Renales/tratamiento farmacológicoAsunto(s)
Riñón , Ultrasonografía , Humanos , Riñón/diagnóstico por imagen , Tamaño de los Órganos , Ultrasonografía/métodosRESUMEN
Sepsis associated Acute kidney injury (AKI) is a common clinical syndrome characterized by suddenly decreased in renal function and urinary volume. This study was designed to investigate the role of Aquaporin 1 (AQP1) and P53 in the development of sepsis-induced AKI and their potential regulatory mechanisms. Firstly, transcriptome sequencing analysis of mice kidney showed AQP1 expression was reduced and P53 expression was elevated in Cecal ligation and puncture (CLP)-induced AKI compared with controls. Bioinformatics confirmed that AQP1 expression was remarkably decreased and P53 expression was obviously elevated in renal tissues or peripheral blood of septic AKI patients. Moreover, we found in vivo experiments that AQP1 mRNA levels were dramatically decreased and P53 mRNA significantly increased following the increased expression of inflammation, apoptosis, fibrosis, NGAL and KIM-1 at various periods in septic AKI. Meanwhile, AQP1 and P53 protein levels increased significantly first and then decreased gradually in kidney tissue and serum of rats in different stages of septic AKI. Most importantly, in vivo and vitro experiments demonstrated that silencing of AQP1 greatly exacerbates renal or cellular injury by up-regulating P53 expression promoting inflammatory response, apoptosis and fibrosis. Overexpression of AQP1 prevented the elevation of inflammation, apoptosis and fibrosis by down-regulating P53 expression in Lipopolysaccharide (LPS)-induced AKI or HK-2 cells. Therefore, our results suggested that AQP1 plays a protective role in modulating AKI and can attenuate inflammatory response, apoptosis and fibrosis via downregulating P53 in septic AKI or LPS-induced HK-2cells. The pharmacological targeting of AQP1 mediated P53 expression might be identified as potential targets for the early treatment of septic AKI.
Asunto(s)
Lesión Renal Aguda , Apoptosis , Acuaporina 1 , Fibrosis , Inflamación , Sepsis , Proteína p53 Supresora de Tumor , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/etiología , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Acuaporina 1/genética , Acuaporina 1/metabolismo , Animales , Sepsis/complicaciones , Sepsis/metabolismo , Ratones , Humanos , Masculino , Ratas , Modelos Animales de Enfermedad , Riñón/patología , Riñón/metabolismo , Ratones Endogámicos C57BL , Ratas Sprague-DawleyRESUMEN
The histological changes in the liver, kidney, spleen, and gills of Syacium papillosum from the continental shelf of the Yucatan Peninsula, Gulf of Mexico, and their statistical associations with environmental conditions and pollutants were assessed in 2010, 2011, and 2012. We evaluated the extension and severity of the lesions through a degree of tissue change (DTC), and, with the sum of the number of lesion types within each of their DTC stages, we determined the histological alteration index (HAI). The liver and kidney were the most affected organs, with HAI values > 100. Fish with the most severe damage were observed on the Campeche Bank and the Caribbean Sea, contrasting with those collected from the northern Yucatan continental shelf. The presence of foci cellular alteration and abundant melanomacrophage centers indicated that these flatfishes were chronically exposed to environmental stress factors. Redundancy analyses showed strong associations between HAI values and hydrocarbon and heavy metal concentrations in muscle. Our results provide evidence for the first time of a differential health condition of the Yucatan shelf through the histopathology shown in S. papillosum, establishing the baseline for future monitoring programs in the region.
Asunto(s)
Monitoreo del Ambiente , Lenguado , Branquias , Riñón , Hígado , Contaminantes Químicos del Agua , Animales , Contaminantes Químicos del Agua/análisis , Riñón/patología , Branquias/patología , Hígado/patología , Estrés Fisiológico , Golfo de México , Bazo/patología , Metales Pesados/análisisRESUMEN
Obstructive uropathy is a common kidney disease caused by elevated hydrostatic pressure (HP), but relevant molecular and cellular mechanisms have not yet been well understood. In this study, we ex vivo investigated the effects of elevated HP on human renal epithelial cells (HREpCs). Primary HREpCs were subjected to 100 cmH2O HP for 8 or 48 h. Then, the cells were cultured without HP stimulation for another 24 h or 72 h. Cell morphology showed almost no change after 8h HP treatment, but exhibited reversible elongation after 48h HP treatment. HP treatment for 8 h increased the expression of TGFB1 and VEGFA but decreased the expression of CSF2 and TGFB2. On the other hand, HP treatment for 48 h downregulated the expression of CSF2, TGFB2, PDGFB, VEGFA, and VEGFB, while upregulated the expression of TGFB3. Interestingly, all changes induced by 48 h HP treatment were detected more severe compared to 8 h HP treatment. In conclusion, elongated ex vivo HP loading to renal epithelial cells induces reversible changes on cell morphology and disturbs the expression of several growth factors, which provides novel mechanistic insight on elevated HP-caused kidney injury such as obstructive uropathy.
Asunto(s)
Células Epiteliales , Presión Hidrostática , Riñón , Humanos , Células Epiteliales/metabolismo , Riñón/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Células Cultivadas , Factor A de Crecimiento Endotelial Vascular/metabolismo , Regulación de la Expresión Génica , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
BACKGROUND: Efficient learning strategies and resource utilization are critical in medical education, especially for complex subjects like renal physiology. This is increasingly important given the rise in chronic renal diseases and the decline in nephrology fellowships. However, the correlations between study time, perceived utility of learning resources, and academic performance are not well-explored, which led to this study. METHODS: A cross-sectional survey was conducted with second-year medical students at the University of Bergen, Norway, to assess their preferred learning resources and study time dedicated to renal physiology. Responses were correlated with end-of-term exam scores. RESULTS: The study revealed no significant correlation between time spent studying and overall academic performance, highlighting the importance of study quality over quantity. Preferences for active learning resources, such as Team-Based Learning, interactive lessons and formative assignments, were positively correlated with better academic performance. A notable correlation was found between students' valuation of teachers' professional competence and their total academic scores. Conversely, perceived difficulty across the curriculum and reliance on self-found online resources in renal physiology correlated negatively with academic performance. 'The Renal Pod', a locally produced renal physiology podcast, was popular across grades. Interestingly, students who listened to all episodes once achieved higher exam scores compared to those who listened to only some episodes, reflecting a strategic approach to podcast use. Textbooks, while less popular, did not correlate with higher exam scores. Despite the specific focus on renal physiology, learning preferences are systematically correlated with broader academic outcomes, reflecting the interconnected nature of medical education. CONCLUSION: The study suggests that the quality and strategic approaches to learning significantly impact academic performance. Successful learners tend to be proactive, engaged, and strategic, valuing expert instruction and active participation. These findings support the integration of student-activating teaching methods and assignments that reward deep learning.
Asunto(s)
Evaluación Educacional , Estudiantes de Medicina , Humanos , Estudios Transversales , Noruega , Masculino , Femenino , Educación de Pregrado en Medicina , Curriculum , Fisiología/educación , Rendimiento Académico , Encuestas y Cuestionarios , Riñón/fisiología , Aprendizaje Basado en ProblemasRESUMEN
BACKGROUND: Chronic kidney disease (CKD) is a significant clinical challenge in Sri Lanka. The present study presents histopathological diagnoses from native renal biopsies in Kandy District, 2011-2020. METHODS: Reports of 5,014 renal biopsies principally performed at Kandy Teaching Hospital over 2011-2020 were reviewed. After exclusions for post-kidney transplant biopsies (1,572) and those without evident pathology (347), 3,095 biopsies were included. The predominant histopathological entities were grouped and categorised according to diagnosis and stratified by age and sex. RESULTS: The main histopathological entities (all biopsies) were tubulointerstitial nephropathy (TIN) 25% (n = 760), glomerulonephritis (GN) 15% (467), lupus nephropathy 14% (429), focal segmental glomerular sclerosis (FSGS) 10% (297), and IgA nephropathy (IgAN) 8% (242). For adult women ≥ 15 years, the main histopathological entities were lupus nephropathy 24% (325), TIN 17% (228), and GN 16% (217). For adult men ≥ 15 years, the main histopathological entities were TIN 34% (449), GN 14% (180), and IgAN 10% (125). The proportion of TIN in the present study was higher than international studies of a similar size. CONCLUSION: This is the largest study of renal biopsies reported from Sri Lanka to date. TIN was the most common diagnosis in adults ≥ 15 years at 25%. Notable sex differences showed TIN was the most common histopathology in men (34%) but not in women (17%). No previously published similar study of this size has found TIN as the predominant diagnosis amongst renal biopsies in men. Further research is required into the possible causes of these observations in Sri Lanka. CLINICAL TRIAL NUMBER: Not applicable.
Asunto(s)
Riñón , Nefritis Intersticial , Humanos , Sri Lanka/epidemiología , Masculino , Adulto , Femenino , Biopsia , Nefritis Intersticial/patología , Nefritis Intersticial/epidemiología , Persona de Mediana Edad , Adulto Joven , Adolescente , Riñón/patología , Nefritis Lúpica/patología , Nefritis Lúpica/epidemiología , Glomerulonefritis por IGA/patología , Glomerulonefritis por IGA/epidemiología , Glomeruloesclerosis Focal y Segmentaria/patología , Glomeruloesclerosis Focal y Segmentaria/epidemiología , Niño , Glomerulonefritis/patología , Glomerulonefritis/epidemiología , Anciano , Factores Sexuales , PreescolarRESUMEN
Kidney injury disrupts the intricate renal architecture and triggers limited regeneration, together with injury-invoked inflammation and fibrosis. Deciphering the molecular pathways and cellular interactions driving these processes is challenging due to the complex tissue structure. Here, we apply single cell spatial transcriptomics to examine ischemia-reperfusion injury in the mouse kidney. Spatial transcriptomics reveals injury-specific and spatially-dependent gene expression patterns in distinct cellular microenvironments within the kidney and predicts Clcf1-Crfl1 in a molecular interplay between persistently injured proximal tubule cells and their neighboring fibroblasts. Immune cell types play a critical role in organ repair. Spatial analysis identifies cellular microenvironments resembling early tertiary lymphoid structures and associated molecular pathways. Collectively, this study supports a focus on molecular interactions in cellular microenvironments to enhance understanding of injury, repair and disease.
Asunto(s)
Comunicación Celular , Microambiente Celular , Riñón , Regeneración , Daño por Reperfusión , Transcriptoma , Animales , Ratones , Regeneración/genética , Daño por Reperfusión/metabolismo , Daño por Reperfusión/genética , Daño por Reperfusión/patología , Riñón/metabolismo , Riñón/patología , Ratones Endogámicos C57BL , Túbulos Renales Proximales/metabolismo , Túbulos Renales Proximales/patología , Masculino , Fibroblastos/metabolismo , Perfilación de la Expresión Génica , Análisis de la Célula Individual , FibrosisAsunto(s)
Hipertensión , Riñón , Simpatectomía , Humanos , Riñón/inervación , Simpatectomía/métodos , Derivación y Consulta , Desnervación/métodosRESUMEN
Dimethyl oxalate is one of the occupational toxic chemicals and causes strong renal toxicity. On May 16, 2023, a patient with acute dimethyl oxalate poisoning was admitted to Dingxi People's Hospital. The patient presented with nausea, vomiting, lumbar distension, weakness, poor appetite, anuria, and rapidly progressing acute kidney injury. Renal biopsy confirmed acute oxalate nephropathy. After symptomatic supportive treatments such as blood purification, anti-oxidative stress, glucocorticoid, fluid supplementation, alkalized urine, anti-infection, controlling blood pressure, calcium supplementation and anemia correction, the patient's symptoms disappeared, and the kidney function basically returned to normal. This case suggested that the etiology of patients with acute kidney injury must be clearly identified, and renal biopsy was an important examination method. For patients suffering from acute dimethyl oxalate poisoning, comprehensive treatment based on blood purification should be performed as soon as possible, aiming to improve the prognosis.
Asunto(s)
Lesión Renal Aguda , Humanos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/terapia , Masculino , Adulto , Riñón/patología , Oxalatos/envenenamientoRESUMEN
OBJECTIVES: Growing evidence has highlighted the substantial effects of COVID-19 on kidneys, ranging from mild proteinuria to severe acute kidney injury. However, comprehensive assessments of histopathological features in renal allograft biopsies are lacking. MATERIALS AND METHODS: Seventeen kidney transplant recipients with COVID-19 between March 2020 and November 2022 were evaluated. Clinical characteristics, pathological findings, and outcomes were studied. RESULTS: Six kidney transplant recipients (35.3%) developed acute kidney injury, leading to the requirement for hemodialysis. COVID-19 severity, as indicated by pneumonia (P = .028) and hospitalization (P = .002), was significantly associated with development of acute kidney injury. Most patients with COVID-19 (82.4%) showed considerably increased proteinuria levels (82.4%), along with presence of new-onset microscopic hematuria (35.3%) and nephrotic syndrome (58.8%). Tubular viral inclusionlike changes were detected in 47.1% of cases and were associated with a higher risk of graft loss (75%). Thrombotic microangiopathy and endothelial cell swelling in glomeruli were prevalent, highlighting extensive endothelial cell injury. Most recipients (88.2%) experienced rejection after COVID-19, with graft loss occurring in 46.7% of these cases. Biopsies revealed collapsing (n = 5), noncollapsing (n = 3), and recurrent (n = 2) focal segmental glomerulosclerosis, as well as acute tubulointerstitial nephritis (n = 3), crescentic glomerulonephritis with immunoglobulin A nephropathy (n = 1), and membranoproliferative glomerulonephritis (n = 1), in 129.7 ± 33 days. Eight patients experienced graft loss (8.2 ± 2 mo posttransplant). Hospitalization (P = .044) and viralinclusion-like nuclear changes in tubules (P = .044) significantly influenced graft survival. Collapsing (60%) and noncollapsing (66.7%) focal segmental glomerulosclerosis increased the risk of graft loss. CONCLUSIONS: COVID-19 has had a multifaceted and enduring effect on renal allografts, urging the need for meticulous monitoring and tailored management strategies to mitigate the risk of severe kidney-related complications and graft loss in this vulnerable population.
Asunto(s)
Lesión Renal Aguda , COVID-19 , Trasplante de Riñón , Humanos , COVID-19/epidemiología , Trasplante de Riñón/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Factores de Riesgo , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Biopsia , Rechazo de Injerto/inmunología , Aloinjertos , Resultado del Tratamiento , Riñón/patología , Riñón/virología , Estudios Retrospectivos , Supervivencia de Injerto , Anciano , Medición de RiesgoRESUMEN
OBJECTIVE: To investigate the accuracy and reproducibility of diaphragmatic excursion (DE) measurements through hepato-renal/spleno-renal section as a novel method for assessing diaphragmatic function. METHODS: Twelve healthy participants were recruited. Each participant underwent DE measurements performed by four operators with varying levels of experience using traditional methods (liver/spleen section) and novel methods (hepato-renal/spleno-renal section), respectively. Among them, two experienced operators were critical care clinicians, and diaphragmatic ultrasound was performed in more than 50 cases. The other two inexperienced operators were respiratory therapists, with less than 10 cases of diaphragmatic ultrasound operations, who received a 2-hour theoretical and operational training before the study. Operators initially used the conventional method with a 1.5-6.0 MHz convex probe in M-mode, placing the sampling line perpendicular to the diaphragm at the point of maximum excursion, and the liver/spleen section DE was determined during normal breathing of participant. Then, they used the novel method with a 1.6-4.5 MHz phased array probe to observe diaphragmatic movement cranio-caudally along the mid-axillary line, employing anatomic M-mode with the sampling line placed perpendicular to the diaphragm at the level of the renal midpoint, and the DE of the hepato-renal/spleno-renal section was measured during normal breathing. The liver and hepato-renal sections were used to assess the right diaphragm, and spleen and spleno-renal sections were used to assess the left diaphragm. Correlation analysis of DE measurements from different sections was conducted using the Deming method, while consistency was assessed using the Bland-Altman method. The consistency of clinical acceptability was defined as the absence of fixed and proportional bias, with a difference of two standard deviations less than 40% of the mean measurement value. Percentage consistency limit = two standard deviations of the differences between measurements/mean measurement value×100%. RESULTS: Four operators performed image scans of DE in all four sections for each of the twelve subjects, with a high DE acquisition rate of 100% (48/48) for hepato-renal and spleno-renal sections, followed by the liver section [91.7% (44/48)] and the spleen section [66.7% (32/48)], particularly for the left diaphragm assessment, where the DE acquisition rate of spleno-renal section was significantly higher than that of traditional spleen section (P < 0.01). The overall measurement results showed that no significant difference was found in DE determined via the hepato-renal and spleno-renal sections using the novel method (cm: 1.64±0.10 vs. 1.55±0.14, P > 0.05), and they were significantly higher than those determined via the conventional liver and spleen sections (cm: hepato-renal section vs. liver section was 1.64±0.10 vs. 1.44±0.09, spleno-renal section vs. spleen section was 1.55±0.14 vs. 1.09±0.14, both P < 0.01). Correlation analysis revealed good correlations of DE between hepato-renal section and spleno-renal section, between liver section and hepato-renal section, between liver section and spleno-renal section (r values were 0.62, 0.59, and 0.42, all P < 0.01). Consistency analysis showed that the consistency in DE between hepato-renal section and spleno-renal section, as well as between liver section and hepato-renal section was good (both % consistency limits < 40%). However, the DE measured in the spleen section were not correlated with the other three sections, and there was no inconsistency (all % consistency limits > 40%). There was no statistically significant difference in DE measured by the four operators in the liver, spleen, hepato-renal, and spleno-renal sections (cm: 1.49±0.34, 1.44±0.37, 1.43±0.30, and 1.40±0.27 in liver section; 1.10±0.36, 1.05±0.18, 1.09±0.22, and 1.06±0.26 in spleen section; 1.67±0.43, 1.57±0.34, 1.63±0.32, and 1.66±0.36 in hepato-renal section; 1.45±0.33, 1.48±0.34, 1.50±0.24, and 1.65±0.26 in spleno-renal section; all P > 0.05). According to the clinically acceptable range of consistency limits, the DE measured by the four operators in all four sections showed good consistency (all % consistency limits < 40%). CONCLUSIONS: The novel method of measuring DE through hepato-renal/spleno-renal sections is accurate, highly reproducible, and has a high acquisition rate, serving as a viable alternative to the conventional method involving the liver/spleen section.
Asunto(s)
Diafragma , Bazo , Ultrasonografía , Humanos , Diafragma/diagnóstico por imagen , Diafragma/fisiología , Adulto , Masculino , Ultrasonografía/métodos , Femenino , Bazo/diagnóstico por imagen , Hígado/diagnóstico por imagen , Adulto Joven , Riñón/diagnóstico por imagen , Reproducibilidad de los ResultadosRESUMEN
A 15-year-old domestic shorthair cat was presented with gastrointestinal signs, polyuria, polydipsia, and weakness. Abdominal bruit ("whooshing" sound from turbulent blood flow) and hypertension (systolic blood pressure: 200 mmHg) were present. A left adrenal gland mass was detected with abdominal ultrasonography; a subsequent CT examination identified a mass and a thrombus in the ipsilateral renal vein. Adrenalectomy and venotomy were completed but nephrectomy was not necessary. Histological diagnosis was an adrenocortical carcinoma. There were no clinical signs at a follow-up examination 30 mo after surgery. Key clinical message: This report describes successful surgical management of feline adrenocortical carcinoma with renal vein invasion without kidney damage. This case suggests that, after correct diagnosis and in well-selected cases, surgery to remove adrenal tumors and thrombi in cats, despite renal vein invasion, can be done with excellent short- and long-term outcomes.
Sauvegarde des reins lors du traitement chirurgical d'un carcinome corticosurrénalien avec invasion des veines rénales chez un chatUn chat domestique à poil court de 15 ans a été présenté avec des signes gastro-intestinaux, une polyurie, une polydipsie et une faiblesse. Des bruits abdominaux (« sifflement ¼ provenant d'un flux sanguin turbulent) et une hypertension (pression artérielle systolique: 200 mmHg) étaient présents. Une masse de la glande surrénale gauche a été détectée à l'échographie abdominale; un examen tomodensitométrique ultérieur a identifié une masse et un thrombus dans la veine rénale ipsilatérale. La surrénalectomie et la veinotomie ont été réalisées mais la néphrectomie n'a pas été nécessaire. Le diagnostic histologique était un carcinome corticosurrénalien. Il n'y avait aucun signe clinique lors d'un examen de suivi 30 mois après l'intervention chirurgicale.Message clinique clé:Ce rapport décrit la prise en charge chirurgicale réussie du carcinome corticosurrénalien félin avec invasion des veines rénales sans lésion rénale. Ce cas suggère qu'après un diagnostic correct et dans des cas bien sélectionnés, une intervention chirurgicale visant à éliminer les tumeurs surrénales et les thrombi chez les chats, malgré l'invasion des veines rénales, peut être réalisée avec d'excellents résultats à court et à long terme.(Traduit par Dr Serge Messier).
Asunto(s)
Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Enfermedades de los Gatos , Venas Renales , Gatos , Animales , Enfermedades de los Gatos/cirugía , Enfermedades de los Gatos/patología , Carcinoma Corticosuprarrenal/veterinaria , Carcinoma Corticosuprarrenal/cirugía , Carcinoma Corticosuprarrenal/patología , Venas Renales/cirugía , Venas Renales/patología , Neoplasias de la Corteza Suprarrenal/veterinaria , Neoplasias de la Corteza Suprarrenal/cirugía , Neoplasias de la Corteza Suprarrenal/patología , Adrenalectomía/veterinaria , Masculino , Riñón/patología , Riñón/cirugía , Invasividad NeoplásicaRESUMEN
ABSTRACT: We aimed to measure cerebral, splanchnic, and renal transit times and the associated blood volumes using contrast ultrasound. In healthy individuals, regional transit times were calculated from time-intensity curves generated as ultrasound contrast passed through the associated inflow and outflow vessels. These included the internal carotid artery and internal jugular vein (brain), the superior mesenteric artery and portal vein (intestines), and the renal artery and renal vein (kidney). An organ's blood volume relative to the stroke volume delivered to that organ with each cardiac cycle was calculated from the product of heart rate and transit time of contrast passage through the associated vascular bed. The fraction of systemic stroke volume received by each organ was calculated from the respective velocity-time integral and inflow vessel cross-sectional area and used to estimate absolute organ blood volume. The cohort consisted of 16 participants (age: 42 ± 13 years; 5 female) without known cerebrovascular, gastrointestinal, or renal disease. Cerebral, splanchnic, and renal transit times were obtained for 15, 14, and 8 individuals, respectively. Anatomic variability of the renal vessels confounded the acquisition of renal transit times. For all organs, transit times were reproducible and the associated blood volumes were generally comparable to reference values. Cerebral, gastrointestinal, and renal transit times/blood volumes can be reasonably acquired from contrast ultrasound, although the latter is less reliably available. Assessment of the impact on regional blood volumes of pharmacologic or other interventions is a next step toward clinical application of this technique.