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1.
Ann Lab Med ; 42(2): 160-168, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635609

RESUMO

Background: Automated urine sediment analysis has been developed to address the limitations of microscopic examination of dysmorphic red blood cells (RBCs). We evaluated the urinary RBC distribution (URD) parameter of a recently launched automated urinary flow cytometry analyzer, UF-5000 (Sysmex, Kobe, Japan), to differentiate glomerular hematuria (GH) from non-GH (NGH). Methods: Samples submitted for urine sediment analysis from patients with hematuria (>20 RBCs/µL) were divided into derivation (N=156; 101 GH, 55 NGH) and validation cohorts (N=107; 60 GH, 47 NGH). The clinical diagnosis of GH or NGH was established based on clinical data review. Differences in UF-5000 parameters (URD, small RBC, lysed RBC, RBC-P70FSC, RBC-SF-FSC-W, mean forward-scattered light, and mean side-scattered light) between GH and NGH, and areas under the ROC curves (AUC) were analyzed in the derivation cohort. The derived ideal cut-off value was evaluated in the validation cohort. We applied the Kitasato criteria to compare the diagnostic performance. Results: URD (%), differed significantly between GH and NGH (P<0.001) in the two cohorts. The AUC of URD was 0.814 and 0.806 in the derivation and validation cohorts, respectively. Using a cut-off of >20.1%, the sensitivity was 99.0%/89.4% and the specificity was 50.9%/63.3% in the derivation/validation cohort. When the Kitasato criteria were applied, the sensitivity and specificity were 80.2% and 52.7%, respectively. Conclusions: URD is a rapid, objective, and quantitative measure that can be used to differentiate GH and NGH.


Assuntos
Hematúria , Nefropatias , Diferenciação Celular , Eritrócitos , Hematúria/diagnóstico , Humanos , Glomérulos Renais
2.
BMC cancer ; 21(1): 575-678, May., 2021. ilus, graf, tab
Artigo em Inglês | Sec. Est. Saúde SP, CONASS, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1224518

RESUMO

BACKGROUND: No biomarker is available for identifying cancer patients at risk of developing nephrotoxicity when treated with cisplatin. METHODS: We performed microRNA (miRNA) sequencing using plasma collected 5 days after cisplatin treatment (D5) from twelve patients with head and neck cancer with and without nephrotoxicity (grade ≥ 2 increased serum creatinine). The most differentially expressed miRNAs between the two groups were selected for quantification at baseline and D5 in a larger cohort of patients. The association between miRNAs and nephrotoxicity was evaluated by calculating the odds ratio (OR) from univariate logistic regression. Receiver operating characteristic curves (ROC) were used to estimate the area under the curve (AUC), sensitivity, and specificity. RESULTS: MiR-3168 (p = 1.98 × 10− 8 ), miR-4718 (p = 4.24 × 10− 5 ), and miR-6125 (p = 6.60 × 10− 5 ) were the most differentially expressed miRNAs and were further quantified in 43, 48, and 53 patients, respectively. The baseline expression of miR-3168 (p = 0.0456, OR = 1.03, 95% CI: 1.00­1.06) and miR-4718 (p = 0.0388, OR = 1.56, 95% CI: 1.03­ 2.46) were associated with an increased risk of nephrotoxicity, whereas miR-6125 showed a trend (p = 0.0618, OR = 1.73, 95% CI: 0.98­3.29). MiR-4718 showed the highest AUC (0.77, 95% CI: 0.61­0.93) with sensitivity of 66.76 and specificity of 79.49. CONCLUSIONS: We have provided evidence of baseline plasmatic expression of miR-3168, miR-6125, and miR-4718 as potential predictors of cisplatin-induced nephrotoxicity.


Assuntos
Cisplatino , MicroRNAs , Nefropatias , Neoplasias
3.
J Am Vet Med Assoc ; 259(10): 1163-1170, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34727086

RESUMO

CASE DESCRIPTION: During the same week, 3 sequential patients (a 10-year-old 8.7-kg spayed female poodle cross [dog 1], 13-year-old 2.6-kg spayed female domestic longhair cat, and 13-year-old 9.0-kg castrated male mixed-breed dog [dog 2]) underwent CT-angiography (day 0) and transarterial embolization (day 1) for nonresectable hepatocellular carcinoma (n = 2) or prostatic carcinoma (1). CLINICAL FINDINGS: Contrast-induced nephropathy (CIN) was suspected in all animals on the basis of higher serum creatinine concentrations after contrast medium administration (exposure), compared with baseline concentrations before exposure, consistent with CIN definitions. The total dose of contrast medium was < 3 mL/kg for each exposure. For all 3 patients, creatinine concentration peaked at a median of 3 days (range, 2 to 3 days) after the first exposure (day 0), and the median absolute and relative increases in creatinine concentration after exposure (vs baseline concentrations before exposure) were 2.9 mg/dL (range, 2.2 to 3.7 mg/dL) and 410% (range, 260 to 720%), respectively. TREATMENT AND OUTCOME: The patients received individually tailored supportive care for acute kidney injury. Serum creatinine concentrations began to improve at a median of 4 days (range, 3 to 4 days) and returned to within reference limits at a median of 7 days (range, 3 to 13 days) following initial exposure. CLINICAL RELEVANCE: CIN should be considered as a potential complication following IV administration of contrast medium. Short-term outcome following CIN can be excellent with supportive care.


Assuntos
Injúria Renal Aguda , Doenças do Gato , Doenças do Cão , Nefropatias , Neoplasias , Injúria Renal Aguda/veterinária , Animais , Doenças do Gato/induzido quimicamente , Doenças do Gato/diagnóstico por imagem , Doenças do Gato/terapia , Gatos , Angiografia por Tomografia Computadorizada/veterinária , Meios de Contraste/efeitos adversos , Angiografia Coronária , Creatinina , Doenças do Cão/induzido quimicamente , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/terapia , Cães , Feminino , Nefropatias/veterinária , Masculino , Neoplasias/veterinária , Fatores de Risco , Tomografia Computadorizada por Raios X
5.
EMBO Mol Med ; 13(11): e14146, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34725920

RESUMO

The mechanisms underlying the development of glomerular lesions during aging are largely unknown. It has been suggested that senescence might play a role, but the pathophysiological link between senescence and lesion development remains unexplained. Here, we uncovered an unexpected role for glomerular endothelial cells during aging. In fact, we discovered a detrimental cross-talk between senescent endothelial cells and podocytes, through PAI-1. In vivo, selective inactivation of PAI-1 in endothelial cells protected glomeruli from lesion development and podocyte loss in aged mice. In vitro, blocking PAI-1 in supernatants from senescent endothelial cells prevented podocyte apoptosis. Consistently, depletion of senescent cells prevented podocyte loss in old p16 INK-ATTAC transgenic mice. Importantly, these experimental findings are relevant to humans. We showed that glomerular PAI-1 expression was predictive of poor outcomes in transplanted kidneys from elderly donors. In addition, we observed that in elderly patients, urinary PAI-1 was associated with age-related chronic kidney disease. Altogether, these results uncover a novel mechanism of kidney disease and identify PAI-1 as a promising biomarker of kidney dysfunction in allografts from elderly donors.


Assuntos
Nefropatias , Podócitos , Idoso , Animais , Senescência Celular , Células Endoteliais , Humanos , Glomérulos Renais , Camundongos , Inibidor 1 de Ativador de Plasminogênio
6.
Acta Biomed ; 92(S1): e2021113, 2021 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-34747383

RESUMO

We report the case of a 29-year-old woman with Wunderlich syndrome, a rare spontaneous renal hemorrhage into the subcapsular and perinephric space. She presented to our emergency department with a sudden and persistent right flank pain in the abscence of abdominal injury. The onset of the symptoms can be insidious and lead to hypovolemic shock. Computed Tomography helps both in the diagnosis, detecting the renal hemorrhage, and contributes to an optimal patient management. Selective arterial embolisation is an efficient technique to stop acute and potential life-threatening hemorrhage and preserve the renal parenchyma.


Assuntos
Nefropatias , Anormalidades Urogenitais , Adulto , Feminino , Hemorragia/diagnóstico por imagem , Hemorragia/etiologia , Hemorragia/terapia , Humanos , Rim/diagnóstico por imagem , Tomografia Computadorizada por Raios X
9.
Am J Case Rep ; 22: e933934, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34748529

RESUMO

BACKGROUND Renal lymphangiectasia is a rare benign disorder with unknown pathophysiology. Renal lymphangiectasia can affect both males and females with no known age predilection. Its diagnosis can be accomplished with radiological images and confirmed by aspiration of lymphatic fluid in certain cases. However, there is no clear presentation to be relied on, apart from incidental findings or presentation of complications, such as hypertension due to mass effect on the kidney or renal failure from chronic compression and obstruction or renal vein thrombosis. Management is directed toward symptomatic relief and protection of the kidneys from failure or obstruction. The timing of possible complications and the duration of conservative therapy are undetermined. CASE REPORT Here, we present a case of a healthy 39-year-old woman with bilateral renal lymphangiectasia. It was initially discovered and confirmed to be lymphangiectasia when she was 13 years old and underwent bilateral renal aspiration. She recently presented to the Emergency Department with abdominal symptoms that were found to be caused by diverticulitis. The radiological images showed the persistence of her previous diagnosis of bilateral renal lymphangiectasia. She has had the same condition for more than 25 years, with no related complications or further intervention beyond conservative management. CONCLUSIONS Renal lymphangiectasia has a benign long-term course with insignificant and minor effects in certain patients regardless of the considerable size of cysts and bilateral involvement of the kidneys. The findings of our case could reassure patients with a diagnosis of a similar condition.


Assuntos
Nefropatias , Linfangiectasia , Adolescente , Adulto , Feminino , Humanos , Rim , Linfangiectasia/diagnóstico , Masculino , Morbidade , Tomografia Computadorizada por Raios X
10.
Clinics (Sao Paulo) ; 76: e2942, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34669873

RESUMO

OBJECTIVES: This study assessed the protective effect of calcium dobesilate against contrast-induced nephropathy (CIN) after coronary angiography (CAG) or percutaneous coronary intervention (PCI) in patients with diabetes and chronic kidney disease (CKD). METHODS: A total of 130 patients with diabetes and CKD estimated glomerular filtration rate: 30-90 mL/min/1.73m2 were enrolled and included in the analysis. They were divided into experimental (n=65) and control groups (n=65). Patients in the experimental group were administered oral calcium dobesilate (500 mg) three times daily for 2 days before and 3 days after the procedure. The serum creatinine (SCr), cystatin C (Cys C), and neutrophil gelatinase-associated lipocalin (NGAL) levels were measured before and after the procedure. RESULTS: The mean SCr level at 24h after the procedure was found to be significantly lower in the experimental group than in the control group (79.1±19.6 µmol/L vs. 87.0±19.3 µmol/L, p=0.023). However, the Cys C and NGAL levels were not significantly different between the two groups at all measurement time points (all p>0.05). The incidence of CIN defined by the SCr level was significantly lower in the experimental group than in the control group (3 [4.6%] vs. 13 [20.0%], p=0.017). However, the incidence of CIN defined by the Cys C level was not statistically different between the two groups (7 [10.8%] vs. 7 [10.8%], p=1.000). CONCLUSIONS: This study revealed that calcium dobesilate has no preventive effect against CIN in patients with diabetes and CKD.


Assuntos
Dobesilato de Cálcio , Diabetes Mellitus , Nefropatias , Intervenção Coronária Percutânea , Insuficiência Renal Crônica , Biomarcadores , Meios de Contraste/efeitos adversos , Angiografia Coronária , Creatinina , Taxa de Filtração Glomerular , Humanos , Insuficiência Renal Crônica/complicações
11.
Zhonghua Er Ke Za Zhi ; 59(9): 804-806, 2021 Sep 02.
Artigo em Chinês | MEDLINE | ID: mdl-34645225
12.
Int J Mol Sci ; 22(19)2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34639117

RESUMO

Leptospirosis is a neglected infectious disease caused by pathogenic species of the genus Leptospira. The acute disease is well-described, and, although it resembles other tropical diseases, it can be diagnosed through the use of serological and molecular methods. While the chronic renal disease, carrier state, and kidney fibrosis due to Leptospira infection in humans have been the subject of discussion by researchers, the mechanisms involved in these processes are still overlooked, and relatively little is known about the establishment and maintenance of the chronic status underlying this infectious disease. In this review, we highlight recent findings regarding the cellular communication pathways involved in the renal fibrotic process, as well as the relationship between renal fibrosis due to leptospirosis and CKD/CKDu.


Assuntos
Fibrose/epidemiologia , Nefropatias/epidemiologia , Leptospira/fisiologia , Leptospirose/complicações , Animais , Fibrose/microbiologia , Humanos , Nefropatias/microbiologia , Leptospirose/microbiologia
13.
Int J Mol Sci ; 22(19)2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34639119

RESUMO

Human liver stem-cell-derived extracellular vesicles (HLSC-EVs) exhibit therapeutic properties in various pre-clinical models of kidney injury. We previously reported an overall improvement in kidney function following treatment with HLSC-EVs in a model of aristolochic acid nephropathy (AAN). Here, we provide evidence that HLSC-EVs exert anti-fibrotic effects by interfering with ß-catenin signalling. A mouse model of AAN and an in vitro pro-fibrotic model were used. The ß-catenin mRNA and protein expression, together with the pro-fibrotic markers α-SMA and collagen 1, were evaluated in vivo and in vitro following treatment with HLSC-EVs. Expression and functional analysis of miR29b was performed in vitro following HLSC-EV treatments through loss-of-function experiments. Results showed that expression of ß-catenin was amplified both in vivo and in vitro, and ß-catenin gene silencing in fibroblasts prevented AA-induced up-regulation of pro-fibrotic genes, revealing that ß-catenin is an important factor in fibroblast activation. Treatment with HLSC-EVs caused increased expression of miR29b, which was significantly inhibited in the presence of α-amanitin. The suppression of the miR29b function with a selective inhibitor abolished the anti-fibrotic effects of HLSC-EVs, resulting in the up-regulation of ß-catenin and pro-fibrotic α-Sma and collagen type 1 genes. Together, these data suggest a novel HLSC-EV-dependent regulatory mechanism in which ß-catenin is down regulated by HLSC-EVs-induced miR29b expression.


Assuntos
Vesículas Extracelulares/fisiologia , Fibrose/prevenção & controle , Nefropatias/prevenção & controle , Fígado/citologia , Células-Tronco/citologia , beta Catenina/metabolismo , Animais , Apoptose , Biomarcadores/metabolismo , Proliferação de Células , Células Cultivadas , Modelos Animais de Doenças , Feminino , Fibrose/etiologia , Fibrose/metabolismo , Fibrose/patologia , Regulação da Expressão Gênica , Humanos , Nefropatias/etiologia , Nefropatias/metabolismo , Nefropatias/patologia , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , MicroRNAs/genética , Células-Tronco/metabolismo , beta Catenina/genética
14.
G Ital Nefrol ; 38(5)2021 Oct 26.
Artigo em Italiano | MEDLINE | ID: mdl-34713643

RESUMO

The increase in patients' average age, the enhancement of anticoagulation therapy and the growth of vascular interventions represent the perfect conditions for the onset of atheroembolic renal disease. AERD is observed in patients with diffuse atherosclerosis, generally after a triggering event such as surgery on the aorta, invasive procedures (angiography, catheterization of the left ventricle, coronary angioplasty) and anticoagulant or fibrinolytic therapy. The clinical signs are heterogeneous, a consequence of the occlusion of downstream small arterial vessels by cholesterol emboli coming from atheromatous plaques of the aorta, or one of its main branches. The proximity of the kidneys to the abdominal aorta, and the high flow of blood they receive, make them a major target organ. For this reason, AERD represents a pathological condition that always needs to be taken into account in the nephropathic patient, although its systemic nature makes the diagnosis difficult. This manuscript presents a review of the existing literature on this pathology, to provide an updated summary of the state of the art: risk factors, diagnostics, histology and therapeutic approaches.


Assuntos
Aterosclerose , Embolia de Colesterol , Nefropatias , Aterosclerose/complicações , Embolia de Colesterol/complicações , Embolia de Colesterol/diagnóstico , Embolia de Colesterol/terapia , Humanos , Rim , Nefropatias/etiologia , Nefropatias/terapia , Fatores de Risco
15.
Int J Mol Sci ; 22(19)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34638634

RESUMO

The hyperfiltration theory has been used to explain the mechanism of low birth weight (LBW)-related nephropathy. However, the molecular changes in the kidney proteome have not been defined in this disease, and early biomarkers are lacking. We investigated the molecular pathogenesis of LBW rats obtained by intraperitoneal injection of dexamethasone into pregnant animals. Normal-birth-weight (NBW) rats were used as controls. When the rats were four weeks old, the left kidneys were removed and used for comprehensive label-free proteomic studies. Following uninephrectomy, all rats were fed a high-salt diet until 9 weeks of age. Differences in the molecular composition of the kidney cortex were observed at the early step of LBW nephropathy pathogenesis. Untargeted quantitative proteomics showed that proteins involved in energy metabolism, such as oxidative phosphorylation (OXPHOS), the TCA cycle, and glycolysis, were specifically downregulated in the kidneys of LBW rats at four weeks. No pathological changes were detected at this early stage. Pathway analysis identified NEFL2 (NRF2) and RICTOR as potential upstream regulators. The search for biomarkers identified components of the mitochondrial respiratory chain, namely, ubiquinol-cytochrome c reductase complex subunits (UQCR7/11) and ATP5I/L, two components of mitochondrial F1FO-ATP synthase. These findings were further validated by immunohistology. At later stages of the disease process, the right kidneys revealed an increased frequency of focal segmental glomerulosclerosis lesions, interstitial fibrosis and tubular atrophy. Our findings revealed proteome changes in LBW rat kidneys and revealed a strong downregulation of specific mitochondrial respiratory chain proteins, such as UQCR7.


Assuntos
Recém-Nascido de Baixo Peso/metabolismo , Nefropatias/metabolismo , Proteoma/metabolismo , Animais , Animais Recém-Nascidos/metabolismo , Biomarcadores/metabolismo , Peso ao Nascer/fisiologia , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Feminino , Rim/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Fosforilação Oxidativa , Gravidez , Proteômica/métodos , Proteína Companheira de mTOR Insensível à Rapamicina/metabolismo , Ratos
16.
J Biomed Nanotechnol ; 17(10): 2071-2084, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34706807

RESUMO

Uric acid is the final product of purine metabolism, and excessive serum uric acid can cause gouty arthritis and uric acid nephropathy. Therefore, lowering the uric acid level and alleviating inflammation in the body are the key points to treating these diseases. A stable nanosuspension of peptide BmK9 was prepared by the precipitation-ultrasonication method. By combining uricase on the surface of a positively charged carrier, a complex consisting of neutral rod-shaped BmK9 and uricase nanoparticles (Nplex) was formed to achieve the delivery of BmK9 and uricase, respectively. The formulation of Nplex has a diameter of 180 nm and drug loading up to 200%, which releases BmK9 and uricase slowly and steadily in drug release tests in vitro. There was significantly improved pharmacokinetic behavior of the two drugs because Nplex prolonged the half-life and increased tissue accumulation. Histological assessments showed that the dual drug Nplex can reduce the inflammation response in acute gouty arthritis and chronic uric acid nephropathy in vivo. In the macrophage system, there was lower toxicity and increased beneficial effect on inflammation with Nplex than free BmK9 or uricase. Collectively, this novel formulation provides a dual drug delivery system that can treat gouty arthritis and uric acid nephropathy.


Assuntos
Artrite Gotosa , Nefropatias , Nanopartículas , Artrite Gotosa/induzido quimicamente , Artrite Gotosa/tratamento farmacológico , Humanos , Urato Oxidase , Ácido Úrico
17.
J Biomed Nanotechnol ; 17(10): 2085-2098, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34706808

RESUMO

With the progress made in the widespread application of interventional radiology procedures, there has been an increasing number of patients who suffer from cardiovascular diseases and go through imaging and interventional treatment with iodine contrast medium (ICM) year by year. In turn, there has been an increasing amount of concern over acute kidney injury (AKI) brought about by ICM. As evidenced by numerous studies, the initiation of inflammatory response plays a critical role in the development of ICM-induced AKI. Correspondingly, the strategy of targeting renal inflammatory response and cytokine release could provide an effective solution to mitigating the ICM-induced AKI. Moreover, Ginsenoside Rb1 (GRb1) constitutes one of the major active components of ginseng and features a wide range of vital biological functions. Judging from the research findings, GRb1 could impose antioxidant and anti-inflammatory effects on cardiovascular diseases, in addition to lung, liver and kidney diseases. However, reports on whether GRb1 could impose a protective effect against contrast-induced nephropathy (CIN) are absent. In this study, we have examined the therapeutic effects imposed by GRb1 as well as the potential molecular mechanism by establishing an in vivo and in vitro model of CIN. In addition, we have set up a mouse model of CIN through sequential intravenous injection of indomethacin, N(ω)-nitro-Larginine methyl ester (L-NAME), and iopromide. To further enhance the bioavailability of GRb1, we have encapsulated GRb1 with polyethylene glycol (PEG)/poly lactic-co-glycolic acid (PLGA) nanocarriers to generate GRb1 nanoparticles (NPs) conducting the in vivo experiments. During the in vitro experiments, we have adopted GRb1 to treat NRK-52E cells or cells transfected with the high mobility group box 1 gene (HMGB1) overexpression plasmid. As shown by the in vivo experimental results, GRb1 NPs could evidently improve the renal dysfunction in CIN, diminish the extent of apoptosis of tubular epithelial cells, and reduce the expression of high mobility group box 1 (HMGB1) and cytokines (tumor necrosis factor (TNF-α), interleukin (IL) 6 and IL-1ß). In addition, GRb1 NPs are found to be capable of preventing the activation of Toll-like receptor 4 (TLR4)/NF-κB signaling pathway triggered by contrast medium. The in vitro experimental results have exactly confirmed the findings of the in vivo experiments. In the meantime, through the observation of the in vitro assays, overexpression of HMGB1 can partially counteract the beneficial effects imposed by GRb1. Judging from our research data, GRb1 could impose a protective effect against CIN by inhibiting inflammatory response via HMGB1/TLR4/NF-κB pathway, whereas HMGB1 constitutes a critical molecular target of GRb1.


Assuntos
Nefropatias , Nanopartículas , Animais , Ginsenosídeos , Humanos , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo , Nanopartículas/toxicidade , Proteínas de Ligação a Retinoblastoma , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Ubiquitina-Proteína Ligases
18.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 50(4): 524-528, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34704408

RESUMO

COVID-19 vaccine, as one of the critical measures to control the pandemic, has been administered in nearly all countries. However, the new-onset and relapsing glomerular diseases associated with COVID-19 vaccination have become a new concern. Both mRNA vaccine and inactivated vaccine may cause new-onset and relapsing glomerular diseases; these diseases would occur after the first dose vaccination or the second dose. New-onset glomerular disease is mainly minimal change glomerulopathy, which is mostly sensitive to steroid, while relapsing cases have good prognosis, and some cases can be spontaneously remitted. The pathogenesis of these vaccine-associated diseases is possibly due to the humoral and cellular immune responses. In this article, we provide a general review of the new-onset and relapsing glomerular diseases related to COVID-19 vaccination, and make suggestions for patients with kidney diseases to receive COVID-19 vaccination.


Assuntos
COVID-19 , Nefropatias , Vacinas contra COVID-19 , Humanos , SARS-CoV-2 , Vacinação/efeitos adversos
19.
J Transl Med ; 19(1): 441, 2021 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-34674704

RESUMO

Podocytes are differentiated postmitotic cells which cannot be replaced after podocyte injury. The mechanism of podocyte repopulation after injury has aroused wide concern. Parietal epithelial cells (PECs) are heterogeneous and only a specific subpopulation of PECs has the capacity to replace podocytes. Major progress has been achieved in recent years regarding the role and function of a subset of PECs which could transdifferentiate toward podocytes. Additionally, several factors, such as Notch, Wnt/ß-catenin, Wilms' tumor-1, miR-193a and growth arrest-specific protein 1, have been shown to be involved in these processes. Finally, PECs serve as a potential therapeutic target in the conditions of podocyte loss. In this review, we discuss the latest observations and concepts about the recruitment of podocytes from PECs in glomerular diseases as well as newly identified mechanisms and the most recent treatments for this process.


Assuntos
Nefropatias , Podócitos , Cápsula Glomerular , Células Epiteliais , Humanos
20.
Int J Mol Sci ; 22(19)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34639002

RESUMO

Renal toxicity is a serious side effect that hinders the use of cisplatin, a commonly used and effective chemotherapeutic agent. Meanwhile, quinacrine is an FDA approved drug that has been stated for its anti-inflammatory effect. Thus, we investigated the ameliorative effect of quinacrine against cisplatin-induced renal toxicity. Single intraperitoneal (i.p.) 10 mg/kg cisplatin administration induced renal injury in rats. Our results showed that 10 mg/kg/day quinacrine decreased the mortality rate of rats from 46.15% (cisplatin group) to 12.5%, and significantly decreased renal tissue fibrosis, relative kidney to body weight ratio, serum creatinine and urea levels compared with the cisplatin group. Indeed, quinacrine significantly decreased renal malondialdehyde concentration and increased renal total antioxidant capacity, compared with the cisplatin group. Furthermore, quinacrine caused significant upregulation of renal sirtuin-1 (SIRT-1) with significant downregulation of intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-α (TNF-α). Moreover, quinacrine significantly blocked cisplatin-induced apoptosis, which was made evident by downregulating renal apoptotic proteins (BAX and p53) and upregulating the renal anti-apoptotic protein BCL2, compared with the cisplatin group. In conclusion, this study demonstrates, for the first time, that quinacrine alleviates cisplatin-induced renal toxicity via upregulating SIRT-1, downregulating inflammatory markers (ICAM-1 and TNF-α), reducing oxidative stress, and inhibiting apoptosis.


Assuntos
Cisplatino/efeitos adversos , Nefropatias/etiologia , Nefropatias/metabolismo , Quinacrina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Fibrose , Imuno-Histoquímica , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Nefropatias/diagnóstico , Nefropatias/tratamento farmacológico , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos
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