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The prognosis of patients with IgA nephropathy (IgAN) is variable but overall not good. Almost all patients with IgAN are at risk of developing end-stage renal disease within their expected lifetime. The models presently available for prediction of the risk of progression of IgAN, including the International IgA Nephropathy Prediction Tool, consist of traditional clinical, pathological, and therapeutic indicators. Finding biomarkers to improve the existing risk prediction models or replace pathological indicators is important for clinical practice. Many studies have attempted to identify biomarkers for prediction of progression of IgAN, such as galactose-deficient IgA1, complement, a spectrum of protein biomarkers, non-coding RNA, and shedding cells. This article reviews the biomarkers of progression of IgAN identified in recent years, with a focus on those with clinical value, in particular the combination of multiple biomarkers into a biomarker spectrum. Future research should focus on establishing a model based primarily on biomarkers that can predict progression of IgAN and testing it in various patient cohorts.
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BACKGROUND: Many guidelines have recommended renin-angiotensin system inhibitors (RASI) as the first-line treatment for patients with chronic kidney disease (CKD). We studied RASI prescription trends from 2010 to 2019, and analyzed the characteristics associated with RASI prescription in Chinese hospitalized CKD patients. AIM: To study the prescription of renin angiotensin system inhibitors in hospitalized patients with CKD in China. METHODS: It was retrospectively, cross-sectional reviewed RASI prescriptions in hospitalized CKD patients in China from 2010 to 2019. RASI prescribing trends were analyzed from 2010 to 2019, and bivariate and multivariate logistic regression analyses were conducted to identify characteristics associated with RASI prescription. RESULTS: A total of 35090 CKD patients were included, with 10043 (28.6%) RASI prescriptions. Among these patients, 18919 (53.9%) met the criteria for RASI treatments based on the 2012 kidney disease: Improving global outcomes guidelines. Of these, 7246 (38.3%) patients received RASI prescriptions. RASI prescriptions showed an initial rapid increase from 2011 to 2012, reached its peak around 2015 and 2016, and then exhibited a subsequent slight decreasing trend. Both bivariate and multivariate analyses showed that several characteristics, including the male gender, age less than 60-year-old, nephrology department admission, lower CKD stage, history of hypertension or diabetes, proteinuria, glomerulonephritis as the CKD etiology, and non-acute kidney injury were associated with RASI prescriptions. CONCLUSION: The frequency of RASI prescriptions showed an initial increase but a slight decreasing trend in more recent years. CKD patients with certain characteristics such as elderly age, advanced disease stage, surgery department admission, or acute kidney injury were less likely to receive RASI prescriptions. In the application of RASI in hospitalized CKD patients is insufficient. The actual clinical practice needs to be improved. The development of related research is helpful to guide the correct choice of clinical treatment strategy.
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Background: For IgA nephropathy (IgAN), tubular atrophy/interstitial fibrosis is the most important prognostic pathological indicator in the mesangial and endocapillary hypercellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy, and presence of crescents (MEST-C) score. The identification of non-invasive biomarkers for tubular atrophy/interstitial fibrosis would aid clinical monitoring of IgAN progression and improve patient prognosis. Methods: The study included 188 patients with primary IgAN in separate confirmation and validation cohorts. The associations of miR-92a-3p, miR-425-5p, and miR-185-5p with renal histopathological lesions and prognosis were explored using Spearman correlation analysis and Kaplan-Meier survival curves. Bioinformatics analysis and dual luciferase experiments were used to identify hub genes for miR-185-5p. The fibrotic phenotypes of tubular epithelial cells were evaluated in vivo and in HK-2 cells. Results: miRNA sequencing and cohort validation revealed that the expression levels of miR-92a-3p, miR-425-5p, and miR-185-5p in urine were significantly increased among patients with IgAN; these levels could predict the extent of tubular atrophy/interstitial fibrosis in such patients. The combination of the three biomarkers resulted in an area under the receiver operating characteristic curve of 0.742. The renal prognosis was significantly worse in the miR-185-5p high expression group than in the low expression group (P=0.003). Renal tissue in situ hybridization, bioinformatics analysis, and dual luciferase experiments confirmed that miR-185-5p affects prognosis in patients with IgAN mainly by influencing expression of the target gene tight junction protein 1 (TJP1) in renal tubular epithelial cells. In vitro experiment revealed that an miR-185-5p mimic could reduce TJP1 expression in HK-2 cells, while increasing the levels of α-smooth muscle actin, fibronectin, collagen I, and collagen III; these changes promoted the transformation of renal tubular epithelial cells to a fibrotic phenotype. An miR-185-5p inhibitor can reverse the fibrotic phenotype in renal tubular epithelial cells. In a unilateral ureteral obstruction model, the inhibition of miR-185-5p expression alleviated tubular atrophy/interstitial fibrosis. Conclusion: Urinary miR-185-5p, a non-invasive biomarker of tubular atrophy/interstitial fibrosis in IgAN, may promote the transformation of renal tubular epithelial cells to a fibrotic phenotype via TJP1.
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Glomerulonefritis por IGA , MicroARNs , Humanos , Glomerulonefritis por IGA/patología , Biomarcadores/orina , Fibrosis , MicroARNs/metabolismo , Atrofia , Colágeno , LuciferasasRESUMEN
Acute kidney injury (AKI) constitutes a significant public health concern, with limited therapeutic options to mitigate injury or expedite recovery. A novel therapeutic approach, local renal treatment, encompassing pharmacotherapy and surgical interventions, has exhibited positive outcomes in AKI management. Peri-renal administration, employing various delivery routes, such as the renal artery, intrarenal, and subcapsular sites, has demonstrated superiority over peripheral intravenous infusion. This review evaluates different drug delivery methods, analyzing their benefits and limitations, and proposes potential improvements. Renal decapsulation, particularly with the availability of minimally invasive techniques, emerges as an effective procedure warranting renewed consideration for AKI treatment. The potential synergistic effects of combined drug delivery and renal decapsulation could further advance AKI therapies. Clinical studies have already begun to leverage the benefits of local renal treatments, and with ongoing technological advancements, these modalities are expected to increasingly outperform systemic intravenous therapy.
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Lesión Renal Aguda , Animales , Humanos , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/cirugía , Sistemas de Liberación de Medicamentos/métodos , Riñón , Investigación Biomédica TraslacionalRESUMEN
PURPOSE: We undertook a multicenter epidemiological survey among hospitalized patients with chronic kidney disease (CKD), aiming to reveal the characteristics of elderly CKD by comparing it with non-elderly CKD. METHODS: Medical records were obtained from 18 military hospitals across China from 1 January 2009 to 31 December 2011. The characteristics of chronic kidney disease in the elderly were analyzed through comparing with those in younger patients with chronic kidney disease. RESULTS: A total of 380,461 hospitalized patients were included in the database, with 25,826 (6.8%) diagnosed with CKD. Unlike non-elderly, the top-three causes of chronic kidney disease among elderly patients were diabetic nephropathy (24.1%), hypertension-related renal impairment (20.9%), and primary glomerular disease (11.1%). 71.6% of the elderly patients with CKD had more than one comorbidities and the number of morbidities increased with age. In-hospital mortality of the elderly was significantly higher than those of younger patients (3.3% vs. 1.0%). Multiple logistic regression analysis showed that age, CKD 5 stage, acidosis, cardiovascular and cerebrovascular diseases, infection disease, neoplasm, and dementia were independent risk factors for death from CKD in the elderly. The median length of stay (LOS) was similar between elderly and younger CKD patients. The median cost was higher for elderly CKD patients than for younger CKD patients. Among elderly individuals with CKD, LOS, and hospitalization costs also increased with an increase in the number of coexisting diseases. CONCLUSIONS: Diabetic nephropathy, and hypertension-related kidney injury were the leading causes of chronic kidney disease in elderly patients, which is different from the non-elderly. Elderly patients with chronic kidney disease were more likely to have a higher burden of comorbidities, which were associated with worse in-hospital outcomes.
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Nefropatías Diabéticas , Hipertensión , Insuficiencia Renal Crónica , Humanos , Anciano , Persona de Mediana Edad , Estudios Transversales , Nefropatías Diabéticas/complicaciones , Tasa de Filtración Glomerular , Insuficiencia Renal Crónica/complicaciones , Hipertensión/complicaciones , Factores de RiesgoRESUMEN
BACKGROUND: In dialysis patients, vascular calcification is a common complication and is closely related to the morbidity and mortality of cardiovascular disease. We performed a systematic review to determine the efficacy and safety of sodium thiosulfate (STS) in the progression of vascular calcification in dialysis patients with end-stage renal disease. METHODS: The PubMed, Web of Science, Embase, Cochrane Library, Wanfang, CNKI, China Biology Medicine disc and Weipu databases were searched up to 9 March 2022 for clinical trials to synthesise findings on the efficacy and safety of STS in the progression of vascular calcification in dialysis patients. The primary outcome was coronary artery calcification scores (CACS) or abdominal aortic calcification scores (AACS) or Kauppila index. The secondary outcome was pulse-wave velocity (PWV). Laboratory data were shown in safety data. A random-effect model was used to provide the summary measures of effect [standardised mean difference (SMD) and 95% confidence interval (CI)]. RESULTS: Seven randomised, controlled trials and one nonrandomised, controlled trial involving 370 patients were included. Six studies reported that the progression of CACS or AACS was slower in the intravenous STS group compared with the control group (SMD -3.24, 95% CI: -5.29, -1.18, p = 0.002). Two studies showed the increase in PWV was less in the STS group compared with the control group (SMD -0.52, 95% CI: -0.92, -0.13, p = 0.009). During the trial period, a lower high-sensitivity C-reactive protein level (SMD 1.61, 95% CI: 0.19, 3.04, p = 0.03), a decrease in serum bicarbonate level (SMD 0.67, 95% CI: 0.22, 1.11, p = 0.003) and an increase in serum phosphate level (SMD -0.32, 95% CI: -0.62, -0.03, p = 0.03) were noted in the intravenous STS group compared with the control group. However, serum calcium and parathyroid hormone levels showed no difference between the two groups after the trials. The most common adverse events were temporary nausea and vomiting, which occurred in 12.5 to 75% of patients. CONCLUSIONS: Intravenous STS may slow down the progression of vascular calcification and ameliorate arterial stiffness in dialysis patients. Reliably defining the efficacy and safety of intravenous STS in attenuating the progression of vascular calcification requires a high-quality trial with a large sample size.
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Purpose: Tacrolimus is recommended by KDIGO Clinical Practice Guidelines as an initial therapy for the treatment of membranous nephropathy (MN). However, little is known about the factors that influence response and recurrence of the disease after tacrolimus therapy, and there are limited data regarding the duration of tacrolimus treatment. Here, we present a real-world retrospective cohort study of 182 MN patients treated with tacrolimus, aiming to assess the efficacy and safety of tacrolimus in the treatment of MN. Patients and Methods: The clinical data of 182 patients with MN treated with tacrolimus and followed up for at least one year were analyzed retrospectively for the efficacy and safety of tacrolimus. Results: The mean follow-up period was 27.3 (19.3-41.6) months. A total of 154 patients (84.6%) achieved complete or partial remission, and 28 patients (15.4%) did not. Multivariate Cox regression analysis showed that male and higher baseline BMI were independently associated with lower, while higher serum albumin was associated with higher probability of remission. Among the responders, 56 patients (36.4%) relapsed. After adjustments for age and sex, Cox regression analysis revealed that the longer period of full-dose tacrolimus was administered, the lower the incidence of relapse. However, high levels of serum creatinine and proteinuria at the onset of tacrolimus discontinuation were risk factors for relapse. During the treatment of tacrolimus, a decline in renal function (≥50% increase in serum creatinine after the onset of tacrolimus treatment) was the most common adverse reaction, observed in 20 (11.0%) patients, followed by elevated blood glucose and infection, but the latter two occurred mostly during treatment with tacrolimus plus corticosteroids. Conclusion: Tacrolimus is effective in the treatment of MN, but the relapse rate is high. Clinical studies with larger sample sizes are needed to further explore the use of tacrolimus in the treatment of membranous nephropathy.
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The most prevalent primary glomerulonephritis and leading cause of end-stage renal disease worldwide is IgA nephropathy (IgAN). More and more studies are describing urinary microRNA (miRNA) as a non-invasive marker for a variety of renal diseases. We screened candidate miRNAs based on data from three published IgAN urinary sediment miRNAs chips. In separate confirmation and validation cohorts, we included 174 IgAN patients, 100 patients with other nephropathies as disease controls (DC), and 97 normal controls (NC) for quantitative real-time PCR. A total of three candidate miRNAs, miR-16-5p, Let-7g-5p, miR-15a-5p were obtained. In both the confirmation and validation cohorts, these miRNAs levels were considerably higher in the IgAN than in NC, with miR-16-5p significantly higher than in DC. The area under the ROC curve for urinary miR-16-5p levels was 0.73. Correlation analysis suggested that miR-16-5p was positively correlated with endocapillary hypercellularity (r = 0.164 p = 0.031). When miR-16-5p was combined with eGFR, proteinuria and C4, the AUC value for predicting endocapillary hypercellularity was 0.726. By following the renal function of patients with IgAN, the levels of miR-16-5p were noticeably higher in the IgAN progressors than in the non- progressors (p = 0.036). Urinary sediment miR-16-5p can be used as noninvasive biomarkers for the assessment of endocapillary hypercellularity and diagnosis of IgA nephropathy. Furthermore, urinary miR-16-5p may be predictors of renal progression.
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Glomerulonefritis por IGA , MicroARNs , Humanos , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/genética , MicroARNs/genética , MicroARNs/orina , Riñón , Biomarcadores/orina , Curva ROCRESUMEN
Damage to peritubular capillaries is a key process that contributes to acute kidney injury (AKI) progression. Vascular endothelial growth factor A (VEGFA) plays a critical role in maintaining the renal microvasculature. However, the physiological role of VEGFA in various AKI durations remains unclear. A severe unilateral ischemiaâreperfusion injury model was established to provide an overview of VEGFA expression and the peritubular microvascular density from acute to chronic injury in mouse kidneys. Therapeutic strategies involving early VEGFA supplementation protecting against acute injury and late anti-VEGFA treatment for fibrosis alleviation were analyzed. A proteomic analysis was conducted to determine the potential mechanism of renal fibrosis alleviation by anti-VEGFA. The results showed that two peaks of extraglomerular VEGFA expression were observed during AKI progression: one occurred at the early phase of AKI, and the other occurred during the transition to chronic kidney disease (CKD). Capillary rarefaction progressed despite the high expression of VEGFA at the CKD stage, and VEGFA was associated with interstitial fibrosis. Early VEGFA supplementation protected against renal injury by preserving microvessel structures and counteracting secondary tubular hypoxic insults, whereas late anti-VEGFA treatment attenuated renal fibrosis progression. The proteomic analysis highlighted an array of biological processes related to fibrosis alleviation by anti-VEGFA, which included regulation of supramolecular fiber organization, cell-matrix adhesion, fibroblast migration, and vasculogenesis. These findings establish the landscape of VEGFA expression and its dual roles during AKI progression, which provides the possibility for the orderly regulation of VEGFA to alleviate early acute injury and late fibrosis.
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Lesión Renal Aguda , Insuficiencia Renal Crónica , Ratones , Animales , Factor A de Crecimiento Endotelial Vascular , Proteómica , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/metabolismo , FibrosisRESUMEN
Acute kidney injury (AKI) is a clinically common kidney disease. Age is an important factor that contributes to the susceptibility to AKI. Mesenchymal stem cells (MSCs) are a promising therapy for AKI, and miRNAs in exosomes (Exos) derived from MSCs are an important aspect of MSC treatment. However, the therapeutic effect of miRNA from MSC-derived Exos on AKI and the related mechanism have not been fully clarified. Whether there is a relationship between the mechanisms of senescence for AKI susceptibility and the therapeutic effect of MSCs has not been studied. We compared the degree of cisplatin-induced AKI injury in young and elderly mice and investigated changes in the expression of p53 and markers of DNA damage and apoptosis, which are important in both senescence and AKI. Ageing mice exhibited increased expression of p53 and pro-apoptosis markers. Upregulation of the senescence-associated DNA damage/p53 pathway may be an important susceptibility factor for cisplatin-induced AKI. Treatment with MSCs can reduce the degree of DNA damage and suppress p53 expression and apoptosis. Upon screening for differentially expressed miRNAs, let-7b-5p levels were found to be lower in aged mice than in young mice, and MSC treatment increased let-7b-5p levels. The presence of let-7b-5p in MSC-derived Exos alleviates tubular epithelial cell apoptosis by inhibiting p53, which reduces DNA damage and apoptosis pathway activity. Let-7b-5p downregulation may lead to increased renal AKI susceptibility, thus indicating that this miRNA is a potential driver of the MSC treatment response in AKI.
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Lesión Renal Aguda , Células Madre Mesenquimatosas , MicroARNs , Ratones , Animales , Cisplatino/efectos adversos , Proteína p53 Supresora de Tumor/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/terapia , Apoptosis , Células Madre Mesenquimatosas/metabolismoRESUMEN
Immune checkpoint inhibitors (ICIs) change the prognosis of many cancer patients. With the increasing use of ICIs, immune-related adverse events are occurring, including acute kidney injury (AKI). This study aimed to assess the incidence of AKI during ICI treatment and its risk factors and impact on mortality. Patients treated with ICIs at the First Medical Center of the Chinese PLA General Hospital from January 1, 2014, to December 30, 2019, were consecutively enrolled, and risk factors affecting AKI development in patients treated with ICIs were analyzed using univariate and multivariate logistic regression. Medical record surveys and telephone inquiry were used for follow-up, and Kaplan-Meier survival analysis and Cox regression were used to analyze independent risk factors for death. Among 1615 patients, 114 (7.1%) had AKI. Multivariate logistic regression analysis showed that anemia, Alb < 30 g/L, antibiotic use, diuretic use, NSAID use and proton pump inhibitor use were independent risk factors for AKI development in patients treated with ICIs. Stage 2 or 3 AKI was an independent risk factor for nonrecovery of renal function after AKI onset. Multivariate Cox regression analysis showed that anemia, Alb < 30 g/L, AKI occurrence, and diuretic use were independent risk factors for death in patients treated with ICIs, while high baseline BMI, other tumor types, ACEI/ARB use, and chemotherapy use were protective factors for patient death. AKI occurs in 7.1% of patients treated with ICIs. Anemia, Alb < 30 g/L, and combined medication use are independent risk factors for AKI in patients treated with ICIs. Anemia, Alb < 30 g/L, AKI occurrence, and diuretic use were independent risk factors for death in patients treated with ICIs.
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Lesión Renal Aguda , Inhibidores de Puntos de Control Inmunológico , Humanos , Estudios Retrospectivos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Incidencia , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/epidemiología , Factores de Riesgo , Pronóstico , Diuréticos/efectos adversosRESUMEN
Background: Acute kidney injury (AKI) is associated with damage to the nephrons and tubular epithelial cells (TECs), which can lead to chronic kidney disease and end-stage renal disease. Identifying new biomarkers before kidney dysfunction will offer crucial insight into preventive and therapeutic options for the treatment of AKI. Early growth response 1 (EGR1) has been found to be a pioneer transcription factor that can sequentially turn on/off key downstream genes to regulate whole-body regeneration processes in the leopard worm. Whether EGR1 modulates renal regeneration processes in AKI remains to be elucidated. Methods: AKI models of ischemia-reperfusion injury (IRI) and folic acid (FA) were developed to investigate the roles of EGR1 in kidney injury and regeneration. To further determine the function of EGR1, Egr1-/- mice were applied. Furthermore, RNA sequencing of renal TECs, Chromatin Immunoprecipitation (ChIP) assay, and Dual-luciferase reporter assay were carried out to investigate whether EGR1 affects the expression of SOX9. Results: EGR1 is highly expressed in the kidney after AKI both in humans and mice through analysis of the Gene Expression Omnibus (GEO) database. Furthermore, we verified that EGR1 rapidly up-regulates in the very early stage of IRI and nephrotoxic models of AKI, and validation studies confirmed the essential roles of EGR1 in renal tubular cell regeneration. Further experiments affirmed that genetic inhibition of Egr1 aggravates the severity of AKI in mouse models. Furthermore, our results revealed that EGR1 could increase SOX9 expression in renal TECs by directly binding to the promoter of the Sox9 gene, thus promoting SOX9+ cell proliferation by activating the Wnt/ß-catenin pathway. Conclusions: Together, our results demonstrated that rapid and transient induction of EGR1 plays a renoprotective role in AKI, which highlights the prospects of using EGR1 as a potential therapeutic target for the treatment of AKI.
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Lesión Renal Aguda , Proteína 1 de la Respuesta de Crecimiento Precoz , Túbulos Renales , Daño por Reperfusión , Factor de Transcripción SOX9 , Lesión Renal Aguda/genética , Lesión Renal Aguda/metabolismo , Animales , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Células Epiteliales/metabolismo , Humanos , Riñón/metabolismo , Riñón/patología , Túbulos Renales/metabolismo , Túbulos Renales/patología , Ratones , Ratones Endogámicos C57BL , Daño por Reperfusión/genética , Daño por Reperfusión/metabolismo , Factor de Transcripción SOX9/genética , Factor de Transcripción SOX9/metabolismo , Regulación hacia Arriba , Vía de Señalización WntRESUMEN
Background: Early prediction of acute kidney injury (AKI) can allow for timely interventions, but there are still few methods that are easy and convenient to apply in predicting AKI, specially targeted at patients with minimal change disease (MCD). Motivated by this, we aimed to develop a predicting model for AKI in patients with MCD within the KDIGO criteria. Methods: Data on 401 hospitalized adult patients, whose biopsy was diagnosed as MCD from 12/31/2010 to 15/7/2021, were retrospectively collected. Among these data, patients underwent biopsy earlier formed the training set (n = 283), while the remaining patients formed the validation set (n = 118). Independent risk factors associated with AKI were analyzed. From this, the prediction model was developed and nomogram was plotted. Results: AKI was found in 55 of 283 patients (19%) and 15 of 118 patients (13%) in the training and validation cohorts, respectively. According to the results from lasso regression and logistic regression, it was found that four factors, including mean arterial pressure, serum albumin, uric acid, and lymphocyte counts, were independent of the onset of AKI. Incorporating these factors, the nomogram achieved a reasonably good concordance index of 0.84 (95%CI 0.77-0.90) and 0.75 (95%CI 0.62-0.87) in predicting AKI in the training and validation cohorts, respectively. Decision curve analysis suggested clinical benefit of the prediction models. Conclusions: Our predictive nomogram provides a feasible approach to identify high risk MCD patients who might develop AKI, which might facilitate the timely treatment.
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Panax notoginseng, a traditional Chinese medicine, exerts beneficial effect on diabetic kidney disease (DKD), but its mechanism is not well clarified. In this study we investigated the effects of ginsenoside Rb1 (Rb1), the main active ingredients of Panax notoginseng, in alleviating podocyte injury in diabetic nephropathy and the underlying mechanisms. In cultured mouse podocyte cells, Rb1 (10 µM) significantly inhibited high glucose-induced cell apoptosis and mitochondrial injury. Furthermore, Rb1 treatment reversed high glucose-induced increases in Cyto c, Caspase 9 and mitochondrial regulatory protein NOX4, but did not affect the upregulated expression of aldose reductase (AR). Molecular docking analysis revealed that Rb1 could combine with AR and inhibited its activity. We compared the effects of Rb1 with eparestat, a known aldose reductase inhibitor, in high glucose-treated podocytes, and found that both alleviated high glucose-induced cell apoptosis and mitochondrial damage, and Rb1 was more effective in inhibiting apoptosis. In AR-overexpressing podocytes, Rb1 (10 µM) inhibited AR-mediated ROS overproduction and protected against high glucose-induced mitochondrial injury. In streptozotocin-induced DKD mice, administration of Rb1 (40 mg·kg-1·d-1, ig, for 7 weeks) significantly mitigated diabetic-induced glomerular injuries, such as glomerular hypertrophy and mesangial matrix expansion, and reduced the expression of apoptotic proteins. Collectively, Rb1 combines with AR to alleviate high glucose-induced podocyte apoptosis and mitochondrial damage, and effectively mitigates the progression of diabetic kidney disease.
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Aldehído Reductasa/antagonistas & inhibidores , Nefropatías Diabéticas/tratamiento farmacológico , Ginsenósidos/uso terapéutico , Podocitos/efectos de los fármacos , Albuminuria/metabolismo , Animales , Apoptosis/efectos de los fármacos , Glucemia/análisis , Western Blotting , Células Cultivadas , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Nefropatías Diabéticas/enzimología , Nefropatías Diabéticas/patología , Citometría de Flujo , Riñón/efectos de los fármacos , Riñón/patología , Masculino , Ratones , Simulación del Acoplamiento Molecular , Podocitos/enzimologíaRESUMEN
BACKGROUND: Erythropoiesis-stimulating agents (ESAs) constitute an important treatment option for anemia in hemodialysis (HD) patients. We investigated the relationships among the dosage of ESA, erythropoietin resistance index (ERI) scores, and mortality in Chinese MHD patients. METHODS: This multicenter observational retrospective study included MHD patients from 16 blood purification centers (n = 824) who underwent HD in 2011-2015 and were followed up until December 31, 2016. We collected demographic variables, HD parameters, laboratory values, and ESA dosages. Patients were grouped into quartiles according to ESA dosage to study the effect of ESA dosage on all-cause mortality. The ERI was calculated as follows: ESA (IU/week)/weight (kg)/hemoglobin levels (g/dL). We also compared outcomes among the patients stratified into quartiles according to ERI scores. We used the Cox proportional hazards model to measure the relationships between the ESA dosage, ERI scores, and all-cause mortality. Using propensity score matching, we compared mortality between groups according to ERI scores, classified as either > or ≤12.80. RESULTS: In total, 824 patients were enrolled in the study; 200 (24.3%) all-cause deaths occurred within the observation period. Kaplan-Meier analyses showed that patients administered high dosages of ESAs had significantly worse survival than those administered low dosages of ESAs. A multivariate Cox regression identified that high dosages of ESAs could significantly predict mortality (ESA dosage >10,000.0 IU/week, HR = 1.59, 95% confidence intervals (CIs) (1.04, 2.42), and p = 0.031). Our analysis also indicated a significant increase in the risk of mortality in patients with high ERI scores. Propensity score matching-analyses confirmed that ERI > 12.80 could significantly predict mortality (HR = 1.56, 95% CI [1.11, 2.18], and p = 0.010). CONCLUSIONS: Our data suggested that ESA dosages >10,000.0 IU/week in the first 3 months constitute an independent predictor of all-cause mortality among Chinese MHD patients. A higher degree of resistance to ESA was related to a higher risk of all-cause mortality.
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Eritropoyetina , Hematínicos , Eritropoyesis , Eritropoyetina/uso terapéutico , Hematínicos/uso terapéutico , Humanos , Diálisis Renal , Estudios RetrospectivosRESUMEN
Renal fibrosis plays a crucial role in the progression of chronic kidney disease and end-stage renal disease. However, because the aetiology of this pathological process is complex and remains unclear, there is still no effective treatment. Cellular senescence and the senescence-associated secretory phenotype (SASP) have been reported to lead to renal fibrosis. This review first discusses the relationships among cellular senescence, the SASP and renal fibrosis. Then, the key role of the SASP in irreversible renal fibrosis, including fibroblast activation and abnormal extracellular matrix accumulation, is discussed, with the results of studies having indicated that inhibiting cellular senescence and the SASP might be a potential preventive and therapeutic strategy for renal fibrosis. Finally, we summarize promising therapeutic strategies revealed by existing research on senescent cells and the SASP, including emerging interventions targeting the SASP, caloric restriction and mimetics, and novel regeneration therapies with stem cells.
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Senescencia Celular , Enfermedades Renales , Matriz Extracelular , Fibrosis , Humanos , Enfermedades Renales/terapia , Fenotipo , Células MadreRESUMEN
BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m2, and 24-hour proteinuria level of 0.5-3.0 g, were recruited in 41 hospitals across 19 provinces in China and were randomly divided into five groups: SYKFT, losartan potassium 50 mg or 100 mg, SYKFT plus losartan potassium 50 mg or 100 mg. MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER: NCT02063100 on ClinicalTrials.gov.
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Medicamentos Herbarios Chinos , Glomerulonefritis , China , Método Doble Ciego , Medicamentos Herbarios Chinos/efectos adversos , Glomerulonefritis/tratamiento farmacológico , Humanos , Medicamentos sin Prescripción , Comprimidos , Resultado del TratamientoRESUMEN
Acute kidney injury (AKI) is a disease that seriously endangers human health. At present, AKI lacks effective treatment methods, so it is particularly important to find effective treatment measures and targets. Bioinformatics analysis has become an important method to identify significant processes of disease occurrence and development. In this study, we analyzed the public expression profile with bioinformatics analysis to identify differentially expressed genes (DEGs) in two types of common AKI models (ischemia-reperfusion injury and cisplatin). DEGs were predicted in four commonly used microRNA databases, and it was found that miR-466 and miR-709 may play important roles in AKI. Then, we found key nodes through protein-protein interaction (PPI) network analysis and subnetwork analysis. Finally, by detecting the expression levels in the renal tissues of the two established AKI models, we found that Myc, Mcm5, E2f1, Oip5, Mdm2, E2f8, miR-466, and miR-709 may be important genes and miRNAs in the process of AKI damage repair. The findings of our study reveal some candidate genes, miRNAs, and pathways potentially involved in the molecular mechanisms of AKI. These data improve the current understanding of AKI and provide new insight for AKI research and treatment.
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Lesión Renal Aguda/genética , Lesión Renal Aguda/metabolismo , MicroARNs/genética , Transcriptoma/genética , Animales , Apoptosis/genética , Biología Computacional , Modelos Animales de Enfermedad , Marcadores Genéticos/genética , Humanos , Ratones , Ratones Endogámicos C57BL , Mapeo de Interacción de Proteínas , Mapas de Interacción de Proteínas/genéticaRESUMEN
Acute kidney injury is a serious health hazard disease due to its complex etiology and lack of effective treatments, resulting in high medical costs and high mortality. At present, a large number of basic research studies on acute kidney injury have been carried out. However, acute kidney injury models established in rodents sometimes do not simulate the course of human disease well. Research in large animal models of acute kidney injury is relatively rare, and methods to build a mature model of acute kidney injury have failed. Because its kidney anatomy and morphology are very similar to those in humans, the mini pig is an ideal animal in which to model kidney disease. Nephrotoxic drug-induced acute kidney injury has a high incidence. In this study, we established models of acute kidney injury induced by two drugs (gentamicin and cisplatin). Finally, the model of cisplatin-induced acute kidney injury was developed successfully, but we found the model of gentamycin-induced acute kidney injury was not reproducible. Compared to other models, these models better represent acute kidney injury caused by antibiotics and chemotherapeutic drugs and provide a basis for the study of new treatments for acute kidney injury in a large animal model.
Asunto(s)
Lesión Renal Aguda , Cisplatino/efectos adversos , Modelos Animales de Enfermedad , Gentamicinas/efectos adversos , Porcinos Enanos/metabolismo , Porcinos/metabolismo , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patología , Animales , Cisplatino/farmacología , Gentamicinas/farmacología , MasculinoRESUMEN
This study aimed to evaluate the clinical characteristics and antihypertensive medications affecting elderly hemodialysis (HD) patient mortality. This retrospective cohort study enrolled patients (≥18 years old) discharged from 15 tertiary general hospitals in China between January 1, 2009, and December 31, 2011. The characteristics of elderly HD patients (≥60 years old) and antihypertensive medications for mortality were analyzed. A total of 7135 patients on maintenance HD, including 2738 elderly patients, were enrolled in this study. The mean levels of hemoglobin, albumin, serum calcium, phosphorus, and parathyroid hormone in elderly group were lower than the younger group (P <0.05). The top two reasons for the hospitalization of elderly patients were infection and cardiovascular disease (CVD). We compared the characteristics of 2492 survived elderly maintenance HD patients and 246 patients who died. Aging [odds ratio OR = 1.59, 95% confidence interval (CI): 1.13-2.24] and central venous catheter (CVC) (OR = 1.62, 95% CI: 1.53-1.72) were independently risk factors for mortality in elderly maintenance HD patients. Maintenance HD patients with high levels of hemoglobin (OR = 0.76, 95% CI: 0.73-0.79), albumin (OR = 0.87, 95% CI: 0.77-0.98), uric acid (OR = 0.90, 95% CI: 0.84-0.9) and those taking angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker (OR = 0.77, 95% CI: 0.58-0.90) had a lower risk of mortality. Other antihypertensive drugs including: ß-blockers, calcium channel blockers, and α-blockers were not significantly associated with mortality (P >0.05). CVD and infection were the most common causes of hospitalization and/or mortality in elderly HD patients. Age, anemia and malnutrition, use of CVCs, and low level of serum uric acid are the risk factors for mortality in elderly maintenance HD patients. Renin-angiotensin system blockade might provide a benefit in protecting elderly maintenance HD patients from mortality.