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Subsequently to the publication of the above paper, the authors drew to the attention of the Editorial Office that they made a couple of errors in terms of the data assembly in Figs. 2 and 4 in their paper; specifically, the Transwell assay data shown for the 'miR-320a+/FoxM1+' panel in Fig. 5D on p. 1923 also appeared as the 'ACTN/NC' data panel in Fig. 4E on the same page (Fig. 4E contained the erroneously duplicated panel). In addition, data featured in Fig. 2D of the above paper were strikingly similar to data that appeared in Fig. 6e of the following paper, published subsequently to this article, written by different authors (although a Dr Shiyue Zhao worked in the molecular biology laboratory of Harbin Medical University from 2017 to 2018, and the research collaboration was conducted with Dr Chenlong Li's research group): Li C, Zheng H, Hou W, Bao H, Xiong J, Che W, Gu Y, Sun H and Liang P: Long non-coding RNA linc00645 promotes. TGF-ß-induced epithelial-mesenchymal transition by regulating miR-205-3p-ZEB1 axis in glioma. Cell Death Dis 10: 17, 2019. Finally, after having conducted an independent investigation of the data in this paper, the Editorial Office noted that one of the Petri dish images in Fig. 2C was also strikingly similar to data that appeared in Fig. 2H of the abovementioned article in the journal Cell Death & Disease. After having considered the authors' request for corrigendum, in view of the problems that were identified with the data, the Editor of Oncology Reports has decided that, owing to a lack of confidence in the presented data, the paper should instead be retracted from the journal. After having informed the authors of this decision, they accepted the decision to retract this paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 40: 19171926, 2018; DOI: 10.3892/or.2018.6597].
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Importance: Lupus nephritis (LN) is typically treated with intravenous cyclophosphamide (IVCY), which is associated with serious adverse effects. Tacrolimus may be an alternative for initial treatment of LN; however, large-scale, randomized clinical studies of tacrolimus are lacking. Objective: To assess efficacy and safety of tacrolimus vs IVCY as an initial therapy for LN in China. Design, Setting, and Participants: This randomized (1:1), open-label, parallel-controlled, phase 3, noninferiority clinical trial recruited patients aged 18 to 60 years with systemic lupus erythematosus and LN class III, IV, V, III+V, or IV+V primarily from outpatient settings at 35 centers in China. Inclusion criteria included body mass index of 18.5 or greater to less than 27, 24-hour urine protein of 1.5 g or greater, and serum creatinine of less than 260 µmol/L. Of 505 patients screened, 191 failed screening (163 ineligible, 25 withdrawn consent, and 3 other reasons). Overall, 314 were randomized. The first patient was enrolled March 10, 2015, and the study finished September 13, 2018. The follow-up period was 24 weeks. Data were analyzed from December 2019 to March 2020. Interventions: Oral tacrolimus (target trough level, 4-10 ng/mL) or IVCY for 24 weeks plus prednisone. Main Outcomes and Measures: Complete or partial response rate at week 24 (prespecified). Results: A total of 314 patients were randomized (158 [50.3%] to tacrolimus and 156 [49.7%] to IVCY). Overall, 299 patients (95.2%) were treated (tacrolimus group, 157 [52.5%]; IVCY group, 142 [47.5%]). Baseline demographic and clinical characteristics were generally similar between groups (mean [SD] age, 34.2 [9.5] years; 262 [87.6%] female). Tacrolimus was found to be noninferior to IVCY for LN response at week 24. There was a complete or partial response rate of 83.0% (117 of 141 patients) in the tacrolimus group and 75.0% (93 of 124 patients) in the IVCY group (difference, 7.1%; 2-sided 95% CI, -2.7% to 16.9%; lower limit of 95% CI greater than -15%). At week 24, least-square mean change in Systemic Lupus Erythematosus Disease Activity Index score was -8.6 with tacrolimus and -6.4 with IVCY (difference, -2.2; 95% CI, -3.1 to -1.3). Changes in other immune parameters and kidney function were generally similar between groups. Serious treatment-emergent adverse events (TEAEs) were reported in 29 patients in the tacrolimus group (18.5%) and 35 patients in the IVCY group (24.6%). Most common serious study drug-related TEAEs were infections (14 [8.9%] and 23 [16.2%], respectively). Seven patients in each group withdrew due to AEs. Conclusions and Relevance: In this study, oral tacrolimus appeared noninferior to IVCY for initial therapy of active LN, with a more favorable safety profile than IVCY. Tacrolimus may be an alternative to IVCY as initial therapy for LN. Trial Registration: ClinicalTrials.gov Identifier: NCT02457221.
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Nefritis Lúpica , Tacrolimus , Adulto , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Quimioterapia Combinada , Femenino , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Nefritis Lúpica/tratamiento farmacológico , Masculino , Tacrolimus/efectos adversos , Tacrolimus/uso terapéutico , Resultado del Tratamiento , Adulto JovenRESUMEN
RATIONALE AND OBJECTIVE: The efficacy of Abelmoschus manihot (AM) in treating of chronic kidney disease (CKD) has been confirmed by prior trials. AM is also commonly combined to other medicines among CKD patients in clinic. This trial aimed at evaluating the safety of AM combination application, and further verifying the efficacy of AM in treating various types of CKD. STUDY DESIGN: A multicentre, prospective, open-label, single-arm trial SETTING AND PARTICIPANTS: Approximately 2000 CKD patients with proteinuria (≥ 150 mg/d), from 105 centres across China INTERVENTIONS: AM was administered to patients three times per day for 24 weeks: the daily dose was based on age (> 12 years old: 2.5 g tid; 6â¼12 years old: 1.5 g tid; 2â¼6 years old: 1 g tid) OUTCOMES: The efficacy outcomes were the change in 24-hour proteinuria and estimated glomerular filtration rate (eGFR) from baseline to week 24. Safety outcomes included adverse events and laboratory tests. RESULTS: 2054 CKD patients from 105 centres were enrolled in this trial, with 1843 (89.7%) completing the 24-week follow-up. The participants' median age was 44 years old and 44.6% were female. Compared to baseline, 24-hour proteinuria decreased 471 mg (95% confident interval, 367 to 575, p < 0.001) at week 24. eGFR did not change significantly relative to baseline with the mean increase as 1.7 ml/min/1.73 m2 (95% confident interval, -0.3 to 3.7, p = 0.09). 902 (43.9%) participants combined medication to AM during follow-up. The total incidence of adverse events was 12.9%; and the most common adverse events were hyperlipidaemia (4.1%), abnormal liver function (2.3%), upper respiratory infection (1.8%), and hyperglycaemia (1.1%). Combined medications did not change the risk for hyperlipidaemia and upper respiratory infection. The combination application with antiplatelet reagents increased the risk of abnormal liver function, and with calcium channel blockers increased the risk of hyperglycaemia. LIMITATIONS: Single-arm clinical trial and short observation time CONCLUSION: We have provided safety information of AM on various types of CKD in a large trial, especially when combination to medications most commonly prescribed to CKD patients. AM also showed to decrease proteinuria with stable kidney function during follow up. AM is a promising treatment for CKD patients.
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INTRODUCTION: Renal ischemia/reperfusion injury (IRI) is the most common cause of acute kidney injury (AKI), and patients with AKI have a high rate of mortality. Apelin is a therapeutic candidate for treatment of IRI and Elabela (ELA) is a recently discovered hormone that also activates the apelin receptor (APJ). We examined the use of ELA as a preventive treatment for IRI using in vitro and in vivo models. METHODS: Male mice were subjected to renal IRI, with or without administration of a stabilized form of ELA (Fc-ELA-21) for 4 days. Renal tubular lesions were measured using H&E staining, reactive oxygen species (ROS) were measured using a dihydroethidium stain assay, and renal cell apoptosis was measured using the TUNEL assay and flow cytometry. Immortalized human proximal tubular epithelial (HK-2) cells were pretreated with or without LY294002 and/or ELA-32, maintained at normoxic or hypoxic conditions, and then returned to normal culture conditions to mimic IRI. Cell apoptosis was determined using the TUNEL assay and cell proliferation was determined using the MTT assay. The levels of Akt, p-Akt, ERK1/2, p- ERK1/2, Bcl-2, Bax, caspase-3 and cleaved caspase-3 were measured using western blotting. RESULTS: Fc-ELA-21 administration reduced renal tissue damage, ROS production, and apoptosis in mice that had renal IRI. ELA-32 reduced HK-2 cell apoptosis and restored the proliferation of cells subjected to IRI. Akt phosphorylation had a role in the anti-apoptotic effect of ELA. CONCLUSION: This study of in vitro and in vivo models of IRI indicated that the preventive and anti-apoptotic effects of ELA were mediated via the PI3K/Akt signaling pathway.
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Lesión Renal Aguda/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Hormonas Peptídicas/farmacología , Daño por Reperfusión/tratamiento farmacológico , Lesión Renal Aguda/patología , Animales , Apoptosis/fisiología , Línea Celular , Proliferación Celular/efectos de los fármacos , Semivida , Humanos , Túbulos Renales/citología , Masculino , Ratones Endogámicos C57BL , Hormonas Peptídicas/química , Hormonas Peptídicas/metabolismo , Hormonas Peptídicas/farmacocinética , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patologíaRESUMEN
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
Pyroptosis is a recently identified type of lytic programmed cell death, in which pores form in the plasma membrane, and cells swell, rupture, and then release their contents, including inflammatory cytokines. Molecular studies indicated that pyroptosis may occur via a gasdermin D (GSDMD) and caspase-1 (Casp1) -dependent classical pathway, a GSDMD and Casp11/4/5-dependent non-classical pathway, or a gasdermin E (GSDME) and Casp3-dependent pathway. Studies of animal models and humans indicated that pyroptosis can exacerbate several complications of diabetes, including diabetic nephropathy (DN), a serious microvascular complication of diabetes. Many studies investigated the mechanism mediating the renoprotective effect of GSDMD regulation in the kidneys of patients and animal models with diabetes. As a newly discovered regulatory mechanism, GSDME and Casp3-dependent pyroptotic pathway in the progression of DN has also attracted people's attention. Z-DEVD-FMK, an inhibitor of Casp3, ameliorates albuminuria, improves renal function, and reduces tubulointerstitial fibrosis in diabetic mice, and these effects are associated with the inhibition of GSDME. Studies of HK-2 cells indicated that the molecular and histological features of secondary necrosis were present following glucose stimulation due to GSDME cleavage, such as cell swelling, and release of cellular contents. Therefore, therapies targeting Casp3/GSDME-dependent pyroptosis have potential for treatment of DN. A novel nephroprotective strategy that employs GSDME-derived peptides which are directed against Casp3-induced cell death may be a key breakthrough. This mini-review describes the discovery and history of research in this pyroptosis pathway and reviews the function of proteins in the gasdermin family, with a focus on the role of GSDME-mediated pyroptosis in DN. Many studies have investigated the impact of GSDME-mediated pyroptosis in kidney diseases, and these studies used multiple interventions, in vitro models, and in vivo models. We expect that further research on the function of GDSME in DN may provide valuable insights that may help to improve treatments for this disease.
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Aquaporin 1 (AQP1) is one member of the aquaporin family, also the deeply studied one. It is widely located on the endothelial cells, but the effect of AQP1 on the peritoneal mesothelial cells (PMCs) after long-term peritoneal dialysis (PD) has not been reported before. We divided normal mice into two groups, control group and dialysis group, to confirm the fibrotic changes and expression of APQ1 on peritoneal mesothelial cells. Then we assigned normal mice and AQP1 knockout mice into four groups: Control group, normal dialysis group, AQP1 knockout control group and AQP1 knockout dialysis group. The two dialysis groups received 4.25% glucose dialysis for 28 days. We found that mice in both dialysis groups showed peritoneal fibrotic changes, which were most severe in the AQP1 knockout dialysis group; the peritoneal thickness in the AQP1 knockout dialysis group was also thicker than that in the dialysis group (P < .05). We used electron microscopy to detect ultrastructural changes and observed changes in microvilli and vacuolar degeneration in mesothelial cells from all groups except the control group. The basement membranes were damaged in the AQP1 knockout dialysis group, and peritoneal mesothelial cells were disrupted and detached in this group. Together our findings indicate that AQP1 plays an important role in maintaining the physiological functions of peritoneal mesothelial cells, and AQP1 can protect mesothelial cells during dialysis.
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Acuaporina 1/metabolismo , Células Endoteliales/metabolismo , Diálisis Peritoneal , Peritoneo/citología , Animales , Modelos Animales de Enfermedad , Células Endoteliales/ultraestructura , Ratones , Ratones Noqueados , Microscopía Electrónica , Microscopía FluorescenteRESUMEN
Emerging evidence shows that the AMP-activated protein kinase (AMPK), a critical energy-sensing switch, plays an important role in the pathogenesis and development of obesity-related renal injury. In this review, we summarized the mechanisms underlying the protective effects of AMPK activation against obesity-related renal injury in preclinical studies, with the main purposes of increasing the understanding of AMPK and providing new insights into the future clinical therapeutic strategies. The renoprotective effects of AMPK mainly act by modulating lipid metabolism and autophagy and suppressing oxidative stress, inflammation, and fibrosis. More importantly, we discussed the recent advances in this field that require further investigation. Firstly, the inhibitory effect of AMPK on ferroptosis is a potential mechanism for its protection against renal injury. Secondly, the effect of AMPK on lipolysis is complex: AMPK induces basal lipolysis but also inhibits stimulated lipolysis. Thirdly, statins may play a renoprotective role by activating AMPK. Fourthly, some microRNAs targeting AMPK mRNA have been implicated in diabetic nephropathy in type 2 diabetes. Further, AMPK can regulate the expression of some microRNAs, suggesting that the stable renoprotective effects of AMPK may benefit from its epigenetic regulation. Lastly, several natural compounds and synthetic drugs have been recognized to protect against obesity-related renal injury by activating AMPK and its downstream pathways in animal models. It remains to be seen if combination of newly identified drugs with traditional renoprotective medicine will have any synergistic therapeutic benefits without adding to side effects.
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Proteínas Quinasas Activadas por AMP/metabolismo , Enfermedades Renales/prevención & control , Obesidad/complicaciones , Animales , Nefropatías Diabéticas/fisiopatología , Modelos Animales de Enfermedad , Humanos , Enfermedades Renales/etiología , Metabolismo de los Lípidos/fisiología , Lipólisis/fisiología , Estrés Oxidativo/fisiología , Transducción de SeñalRESUMEN
Sulforaphane (SFN) prevents diabetic nephropathy (DN) in type 2 diabetes (T2D) by up-regulating nuclear factor (erythroid-derived 2)-like 2 (Nrf2). AMP-activated protein kinase (AMPK) can attenuate the pathogenesis of DN by improving renal lipotoxicity along with the activation of Nrf2-mediated antioxidative signaling. Therefore, we investigated whether AMPKα2, the central subunit of AMPK in energy metabolism, is required for SFN protection against DN in T2D, and whether potential cross-talk occurs between AMPKα2 and Nrf2. AMPKα2 knockout (Ampkα2-/-) mice and wildtype (WT) mice were fed a high-fat diet (HFD) or a normal diet (ND) to induce insulin resistance, followed by streptozotocin (STZ) injection to induce hyperglycemia, as a T2D model. Both T2D and control mice were treated with SFN or vehicle for 3 months. At the end of the 3-month treatment, all mice were maintained only on HFD or ND for an additional 3 months without SFN treatment. Mice were killed at sixth month after T2D onset. Twenty-four-hour urine albumin at third and sixth months was significantly increased as renal dysfunction, along with significant renal pathological changes and biochemical changes including renal hypertrophy, oxidative damage, inflammation, and fibrosis in WT T2D mice, which were prevented by SFN in certain contexts, but not in Ampkα2-/- T2D mice. SFN prevention of T2D-induced renal lipotoxicity was associated with AMPK-mediated activation of lipid metabolism and Nrf2-dependent antioxidative function in WT mice, but not in SFN-treated Ampkα2-/- mice. Therefore, SFN prevention of DN is AMPKα2-mediated activation of probably both lipid metabolism and Nrf2 via AMPK/AKT/glycogen synthase kinase (GSK)-3ß/Src family tyrosine kinase (Fyn) pathways.
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Proteínas Quinasas Activadas por AMP/metabolismo , Antioxidantes/metabolismo , Diabetes Mellitus Tipo 2/prevención & control , Nefropatías Diabéticas/prevención & control , Isotiocianatos/uso terapéutico , Metabolismo de los Lípidos , Redes y Vías Metabólicas , Factor 2 Relacionado con NF-E2/metabolismo , Animales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/enzimología , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/enzimología , Fibrosis , Eliminación de Gen , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Inflamación/complicaciones , Inflamación/patología , Isotiocianatos/farmacología , Riñón/anomalías , Riñón/efectos de los fármacos , Riñón/patología , Metabolismo de los Lípidos/efectos de los fármacos , Redes y Vías Metabólicas/efectos de los fármacos , Ratones Endogámicos C57BL , Ratones Noqueados , Modelos Biológicos , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/farmacología , Sustancias Protectoras/uso terapéutico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-fyn/metabolismo , Sulfóxidos , Activación Transcripcional/efectos de los fármacosRESUMEN
Endotoxemia-induced acute kidney injury (AKI) is a common clinical condition that lacks effective treatments. Elabela (ELA) is a recently discovered kidney peptide hormone, encoded by the gene apela, and has been reported to improve cardio-renal outcomes in sepsis. However, ELA is a small peptide and is largely unsuitable for clinical use because of its short in vivo half-life. In the present study, we evaluated the potential renoprotective effects of a long-acting constant fragment (Fc)-ELA fusion protein in liposaccharide (LPS)-induced AKI in mice. LPS administration in mice for 5 days greatly lowered the gene expression of apela and impaired kidney function, as evidenced by elevated serum creatinine and the ratio of urine protein to creatinine. In addition, renal inflammation and macrophage infiltration were apparent in LPS-challenged mice. Treatment with the Fc-ELA fusion protein partially restored apela expression and attenuated the kidney inflammation. Moreover, LPS treatment induced reactive oxygen species (ROS) production and apoptosis in kidney HK-2 cells as well as in the mouse kidney, which were mitigated by ELA or Fc-ELA treatment. Finally, we found that ELA promoted the survival of HK-2 cells treated with LPS, and this action was abolished by LY204002, a PI3K/Akt inhibitor. Collectively, we have demonstrated that the Fc-ELA fusion protein has significant renoprotective activities against LPS-induced AKI in mice.
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Lesión Renal Aguda/tratamiento farmacológico , Fragmentos Fc de Inmunoglobulinas/genética , Lipopolisacáridos/toxicidad , Hormonas Peptídicas/genética , Proteínas Recombinantes de Fusión/farmacología , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/genética , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Femenino , Expresión Génica/efectos de los fármacos , Humanos , Fragmentos Fc de Inmunoglobulinas/farmacología , Túbulos Renales Proximales/citología , Túbulos Renales Proximales/efectos de los fármacos , Túbulos Renales Proximales/metabolismo , Ratones Endogámicos C57BL , Hormonas Peptídicas/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Sustancias Protectoras/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteínas Recombinantes de Fusión/genéticaRESUMEN
AIMS: Obesity-related glomerulopathy (ORG) is characterized by glomerulomegaly with or without focal and segmental glomerulosclerosis lesions. Isothiocyanate sulforaphane (SFN) can protect kidneys from ORG-related damages. In this study, we investigated the effects of SFN as a preventive therapy or intervention for ORG to reveal its mechanism of action. MAIN METHODS: We established a mouse obesity model with preventive SFN or N-acetylcysteine treatment for 2 months. Thereafter, we used nuclear factor erythroid 2-related factor 2-deficient (Nrf2-/-) and wild type mice in our ORG model with SFN treatment. Finally, we generated a corresponding mouse podocyte model in vitro. The body weight, wet weight of perirenal-and peritesticular fat, and urinary albumin/creatinine ratio were assessed. We used periodic acid-Schiff staining and electron microscopy to assess the function of the kidneys and podocytes. In addition, we evaluated the expression of Nrf2 and podocyte-specific proteins by western blotting. KEY FINDINGS: Treatment with SFN reduced body weight, organ-associated fat weight, and urinary albumin/creatinine ratio in both the preventive treatment and disease intervention regimens. SFN treated mice exhibited higher expression levels of podocyte-specific proteins and better podocyte function. However, treatment with SFN did not affect these parameters in obese Nrf2-/- mice. Light chain 3 of microtubule-associated protein 1-II and metallothionein had higher expression in the wild type than in the Nrf2-/- mice. SIGNIFICANCE: Treatment with SFN limited ORG-induced damage by enhancing podocyte autophagy via Nrf2.
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Isotiocianatos/uso terapéutico , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/etiología , Factor 2 Relacionado con NF-E2/metabolismo , Obesidad/complicaciones , Sustancias Protectoras/uso terapéutico , Animales , Autofagia/efectos de los fármacos , Células Cultivadas , Enfermedades Renales/metabolismo , Glomérulos Renales/citología , Glomérulos Renales/efectos de los fármacos , Glomérulos Renales/metabolismo , Masculino , Ratones Endogámicos C57BL , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Podocitos/citología , Podocitos/efectos de los fármacos , Podocitos/metabolismo , SulfóxidosRESUMEN
PURPOSE: The association of serum elabela (ELA) and apelin with the progression of chronic kidney disease (CKD) is unknown. We determined if serum ELA and apelin levels were associated with CKD stage. METHODS: This observational study involved 60 CKD patients and 20 healthy, age-, race-, and gender-matched controls. The participants were grouped according to renal function as follows: normal control group, CKD1 group (stage-1 CKD, 20 patients), CKD3 group (stage-3 CKD, 20 patients), and CKD5 group (stage-5 CKD, 20 patients) in accordance with the Kidney Disease Outcomes - Quality Initiative criteria. We recorded the demographic, clinical, and biochemical data of all participants. Serum ELA and apelin levels were measured using commercially available enzyme-linked immunosorbent assays. RESULTS: Serum ELA levels gradually and significantly declined with decreases in the estimated glomerular filtration rate (eGFR). Serum ELA showed significant negative correlations with serum creatinine (r = -0.529, p < .001), blood urea nitrogen (r = -0.575, p < .001), systolic blood pressure (r = -0.455, p < .001), and diastolic blood pressure (r = -0.450, p < .001), and significant positive correlations with hemoglobin (r = 0.523, p < .001) and eGFR (r = 0.728, p < .001). Multiple regression analysis showed that eGFR independently influenced serum ELA levels. No significant association was found between serum apelin levels and CKD progression. CONCLUSION: In CKD patients, serum ELA levels decreased with decreasing eGFR. This finding may provide a new target for the prediction, diagnosis, and staging of CKD.
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Apelina/sangre , Tasa de Filtración Glomerular , Hormonas Peptídicas/sangre , Insuficiencia Renal Crónica/sangre , Adulto , Anciano , Biomarcadores/sangre , Presión Sanguínea , Nitrógeno de la Urea Sanguínea , Estudios de Casos y Controles , Creatinina/sangre , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/fisiopatologíaRESUMEN
BACKGROUND: The current study aims to observe the correlation between the expression of miR-152-5p in urine samples and the condition of IgA nephropathy (IgAN). METHODS: From January 2017 to October 2017, 40 patients with IgAN, 10 patients with mild glomerular lesions, 10 patients with membranous proliferative glomerulonephritis type I, 10 patients with focal segmental glomeruloscle-rosis, 10 patients with Henoch-Schonlein purpura nephritis, and 10 patients with lupus nephritis. Meanwhile, 25 healthy controls were also included in the physical examination center of our hospital. The expression level of miR-152-5p was detected by RT-qPCR. The correlation between the expression level of miR-152-5p and patholog-ical Haas grading and urinary protein was analyzed. RESULTS: The expression level of miR-152-5p in IgA nephropathy patients was higher than that in other types of glomerulonephritis and healthy control group (p < 0.0001). Meanwhile, the level of miR-152-5p in IgAN patients with high score (p < 0.01) was significantly increased. Furthermore, the level of miR-152-5p was positively corre-lated with the level of urinary protein and the degree of renal pathological damage (r2 = 0.89, p < 0.01). CONCLUSIONS: The expression of urinary miR-152-5p is positively correlated with IgA nephropathy, which provides a new way for early diagnosis and treatment of IgA nephropathy with elevated proteinuria.
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Regulación de la Expresión Génica , Glomerulonefritis por IGA/genética , MicroARNs/genética , Proteinuria/genética , Adulto , Femenino , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/orina , Humanos , Riñón/metabolismo , Riñón/patología , Masculino , MicroARNs/orina , Persona de Mediana Edad , Proteinuria/orina , Adulto JovenRESUMEN
Both obesity and arsenic exposure are global public health problems that are associated with increased risk of renal disease. The effect of whole-life exposure to environmentally relevant levels of arsenic within dietary high fat diet on renal pathogenesis were examined. In this study, C57BL/6â¯J mice were parentally exposed to 100â¯ppb arsenic before conception. After weaning, both male and female offspring were maintained on 100â¯ppb arsenic and fed either a normal (LFD) or high fat diet (HFD). At 10 and 24 weeks of age, the offspring were sacrificed and kidneys collected. Exposure to arsenic led to an increase body-weight in LFD diet-fed female but not male mice. This response was not observed in HFD-fed female mice; however male mice showed significant increases in body weight in both As- and non-treated animals. Histological analysis shows that arsenic exposure significantly increases HFD-induced glomerular area expansion, mesangial matrix accumulation and fibrosis compared to LFD control animals. HFD alone increases renal inflammation and fibrosis; reflected by increases in IL-1ß, ICAM-1 and fibronectin levels. Arsenic exposure significantly increases HFD-induced inflammatory and oxidative stress responses. In general, male mice have more severe responses than female mice to HFD or arsenic treatment. These results demonstrate that arsenic exposure causes sex-dependent alterations in HFD-induced kidney damage.
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Arsénico/efectos adversos , Dieta Alta en Grasa/efectos adversos , Enfermedades Renales/etiología , Riñón/efectos de los fármacos , Animales , Arsénico/toxicidad , Peso Corporal/efectos de los fármacos , Inflamación/etiología , Riñón/lesiones , Enfermedades Renales/inducido químicamente , Enfermedades Renales/patología , Ratones , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Factores SexualesRESUMEN
Renal fibrosis is a common pathological feature of chronic kidney disease (CKD) patients who progress to end-stage renal disease (ESRD). With the increasing incidence of CKD, it is of importance to develop effective therapies that blunt development of renal fibrosis. FFNT25 is a newly developed molecular compound that could be used to prevent fibrosis. In this study, we administered FFNT25 to rats following unilateral ureteral obstruction (UUO) to investigate its anti-fibrosis mechanism. Thirty-two Sprague-Dawley rats were randomly divided into four groups: (1) control (normal rats), (2) sham-operated, (3) UUO-operated + vehicle, and (4) UUO-operated + FFNT25. Two weeks after UUO, the rats were gavaged with either FFNT25 (20.6 mg/kg/day) or vehicle for two weeks. Serum, urine, and kidney samples were collected at the end of the study. FFNT25 reduced levels of renal fibrosis and decreased mRNA and protein levels of extracellular matrix (ECM) markers α-smooth muscle actin (α-SMA) and plasminogen activator inhibitor-1 (PAI-1) following UUO compared to vehicle treatment (n = 8, p<.05). The current results indicate that FFNT25 can affect both the production and degradation of collagen fibers to reduce fibrosis.
Asunto(s)
Riñón/patología , Inhibidor 1 de Activador Plasminogénico/metabolismo , Insuficiencia Renal Crónica/tratamiento farmacológico , Inhibidores de Serina Proteinasa/farmacología , Actinas/antagonistas & inhibidores , Actinas/metabolismo , Animales , Colágeno/metabolismo , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Fibrosis , Humanos , Riñón/efectos de los fármacos , Masculino , Proteolisis/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Insuficiencia Renal Crónica/etiología , Insuficiencia Renal Crónica/patología , Inhibidores de Serina Proteinasa/uso terapéutico , Transducción de Señal/efectos de los fármacos , Resultado del Tratamiento , Obstrucción Ureteral/complicacionesRESUMEN
Diabetic nephropathy is a common complication of diabetes characterized by an increased rate of protein excretion in urine and kidney function loss. Elabela is a newly discovered peptide whose role in the regulation of diabetes is the major focus of this research. We established an in vivo model of Type 1 diabetes mellitus by injecting mice intraperitoneally with streptozotocin. The treatment group was administered Elabela for 6 months. In the present study, Elabela administration under diabetic conditions was found to reduce renal inï¬ammation and fibrosis markers, leading to improvement in renal pathology and kidney dysfunction. Furthermore, Elabela acts through the phosphoinositide 3-kinase /Akt/mammalian target of rapamycin signaling pathway and decreases podocyte apoptosis, thereby exhibiting a nephroprotective effect against diabetic nephropathy. Our findings provide the first evidence that Elabela has a potential renoprotective effect in patients of diabetes.
Asunto(s)
Diabetes Mellitus Experimental/fisiopatología , Diabetes Mellitus Tipo 1/fisiopatología , Riñón/efectos de los fármacos , Podocitos/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Nefropatías Diabéticas/patología , Nefropatías Diabéticas/prevención & control , Fibrosis , Riñón/metabolismo , Riñón/patología , Masculino , Ratones Endogámicos C57BL , Nefritis/tratamiento farmacológico , Nefritis/etiología , Estrés Oxidativo/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Podocitos/metabolismo , Podocitos/patología , Sustancias Protectoras/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
AIM: Successful catheter implantation is highly essential for delivering effective peritoneal dialysis (PD). The aim of the present study was to describe a newly developed, minimally invasive percutaneous technique for providing safe, timely, and effective peritoneal catheter insertion and assess the long-term outcome. MATERIALS AND METHODS: 100 PD catheters were placed in 100 consecutive patients by a nephrologist using the modified percutaneous technique with a special trocar, from August 1, 2010 to December 31, 2011. The patients were followed up until October 31, 2015. Demographic and clinical features of study subjects, duration of hospital stay, follow-up time, complications, and catheter survival were assessed in all patients. RESULTS: The patient study group included 47 men and 53 women, with a mean age of 55.3 ± 13.7 years. The mean hospitalization time was 17.1 ± 8.6 days, and the mean duration of follow-up was 44.7 ± 15.1 months. 71 patients were still on continuous ambulatory peritoneal dialysis at the time of study completion. Peritonitis was the most common complication observed, with an incidence of 28%. None of the patients experienced surgical complications such as bleeding or incisional hernia. The mean catheter survival time was 57.0 ± 1.5 months. CONCLUSION: Peritoneal catheter placement using our modified percutaneous technique is simple, safe, minimally invasive, and efficient. It carried less morbidity with respect to bowel perforation, catheter-related infection, and exit-site leak.â©.
Asunto(s)
Cateterismo/métodos , Catéteres de Permanencia/efectos adversos , Diálisis Peritoneal Ambulatoria Continua/métodos , Peritoneo/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cateterismo/efectos adversos , Falla de Equipo/estadística & datos numéricos , Femenino , Humanos , Fallo Renal Crónico/terapia , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Proyectos Piloto , Complicaciones Posoperatorias/epidemiología , Análisis de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: Automated peritoneal dialysis (APD) can cater to individual needs, provide treatment while asleep, take into account the adequacy of dialysis, and improve the quality of life. Currently, independent research and development of APD machines made in China are more conducive to patients. A randomized, multicenter, crossover study was conducted by comparing an APD machine made in China with an imported machine. The safety, effectiveness, and manipulability of the two machines were compared. METHODS: Two hundred and sixty patients who underwent peritoneal dialysis (PD) on a regular basis in 18 centers between August 2015 and February 2016 were included. The inclusion criteria include age ≥18 years and PD ≥30 days. The exclusion criteria were as follows: hemodialysis; exit site or tunnel infection; and peritonitis ≤30 days. The patients were randomly divided into Group A, who were first treated with a FM machine made in China, then changed to an imported machine; and Group B, who were treated using the reverse sequence. APD treatment was performed with 10 L/10 h and 5 cycles of exchange. After 72 h, the daily peritoneal Kt/V, the accuracy of the injection rate, accuracy of the injection temperature, safety, and manipulability of the machine were assessed. Noninferiority test was conducted between the two groups. RESULTS: The daily peritoneal Kt/V in the APD machine made in China and the imported APD machine were 0.17 (0.14, 0.25) and 0.16 (0.13, 0.23), respectively. There was no significant difference between the groups (Z = 0.15, P = 0.703). The lower limit of the daily Kt/V difference between the two groups was 0.0069, which was greater than the noninferiority value of -0.07 in this study. The accuracy of the injection rate and injection temperature was 89.7% and 91.5%, respectively, in the domestic APD machine, which were both slightly better than the accuracy rates of 84.0% and 86.8% in the imported APD machine (89.7% vs. 84.0%, P = 0.2466; 91.5% vs. 86.8%, P = 0.0954). Therefore, the APD machine made in China was not inferior to the imported APD machine. The fuselage of the imported APD machine was space-saving, while the APD machine made in China was superior with respect to body mobility, man-machine dialog operation, alarm control, and patient information recognition. CONCLUSIONS: The FM machine made in China was not inferior to the imported APD machine. In addition, the FM machine made in China had better operability. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02525497; https://clinicaltrials.gov/ct2/results?cond=&term=NCT02525497&cntry=& state=&city=&dist=.
Asunto(s)
Diálisis Peritoneal/efectos adversos , Diálisis Peritoneal/instrumentación , Adulto , China , Estudios Cruzados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Diálisis Peritoneal/métodos , Calidad de Vida , TemperaturaRESUMEN
The Apelin/APJ system is involved in a wide range of biological functions. For a long time, Apelin was thought to be the only ligand for APJ. Recently, a new peptide that acts via APJ and has similar functions, called Elabela, was identified. Elabela has beneficial effects on body fluid homeostasis, cardiovascular health, and renal insufficiency, as well as potential benefits for metabolism and diabetes. In this review, the properties and biological functions of this new peptide are discussed in comparison with those of Apelin. Important areas for future study are also discussed, with the consideration that research on Apelin could guide future research on Elabela.