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1.
J Bras Nefrol ; 44(1): 9-18, 2022.
Artigo em Inglês, Português | MEDLINE | ID: mdl-34289007

RESUMO

INTRODUCTION: Aminoglycoside-induced acute kidney injury (AKI) is a pathology closely linked to oxidative and inflammatory reactions. Taking into account the previous reported antioxidant and anti-inflammatory effects of D-005, a lipid extract obtained from Cuban palm Acrocomia crispa (Arecaceae) fruits, this work aimed to evaluate the effects of D-005 on kanamycin-induced AKI. METHODS: Male Wistar rats were divided into 7 groups: negative control (vehicle, Tween 65/H2O) and six groups treated with kanamycin to induce AKI: positive control (vehicle), D-005 (25, 100, 200, and 400 mg/kg) and grape seed extract (GSE, 200 mg/kg). D-005, vehicle, and GSE oral treatments were administered once daily for seven days, 1 h before kanamycin (500 mg/kg, i.p.). Serum uric acid and urea concentrations, renal histopathology, and oxidative markers (malondialdehyde (MDA), sulfhydryl (SH) groups, and catalase (CAT) activity) were assessed. RESULTS: D-005 significantly reduced uric acid and urea levels, starting from D-005 100 mg/kg. Histopathologically, D-005, at all the tested doses, protected renal parenchyma structures (glomeruli, proximal tubules, and interstitium). These findings were accompanied by a significant reduction of MDA and SH group concentrations as well as restoration of CAT activity. The highest percentages of inhibition were obtained with the dose of 400 mg/kg. GSE, the reference substance, also prevented kanamycin-induced biochemical and histopathological changes, as well as reduced MDA and SH groups and restored CAT activity. CONCLUSION: The administration of repeated oral doses of D-005 significantly protected against kanamycin-induced AKI, which could be associated with the antioxidant and anti-inflammatory effects of this extract.


Assuntos
Injúria Renal Aguda , Arecaceae , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/prevenção & controle , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Frutas , Humanos , Rim/patologia , Lipídeos/farmacologia , Masculino , Malondialdeído , Estresse Oxidativo , Ratos , Ratos Wistar , Ácido Úrico
2.
PLoS One ; 17(9): e0273671, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36054109

RESUMO

BACKGROUND: In nephrotic range proteinuria of adult-onset, kidney biopsy is the diagnostic gold standard in determining the underlying cause of disease. However, in low grade or subnephrotic proteinuria the diagnostic value of kidney biopsy as first-line diagnostics is less well established. METHODS: We conducted a retrospective analysis of all native kidney biopsies at our institution (n = 639) between 01/2012 and 05/2021 for comparison of histological diagnoses and clinical outcomes stratified by amount of proteinuria at the time of kidney biopsy: A: <300mg/g creatinine (low grade), B: 300-3500mg/g creatinine (subnephrotic), C >3500mg/g creatinine (nephrotic). RESULTS: Nephrotic range proteinuria was associated with the highest frequency (49.3%) of primary glomerulopathies followed by subnephrotic (34.4%) and low grade proteinuria (37.7%). However, within the subnephrotic group, the amount of proteinuria at kidney biopsy was linearly associated with renal and overall survival (HR 1.05 per Δ100mg protein/g creatinine (95% CI: 1.02-1.09, p = 0.001)) independent of present histological diagnoses and erythrocyturia. CONCLUSION: Frequency of primary glomerulopathies supports to perform kidney biopsy in patients with subnephrotic proteinuria. These patients have a substantial risk of ESKD and death upon follow-up. Therefore, diagnostic accuracy including histopathology is essential to guide personalized treatment and avert detrimental courses.


Assuntos
Nefropatias , Síndrome Nefrótica , Adulto , Biópsia/efeitos adversos , Creatinina , Humanos , Rim/patologia , Nefropatias/patologia , Síndrome Nefrótica/patologia , Proteinúria/patologia , Estudos Retrospectivos
3.
J Assoc Physicians India ; 70(8): 11-12, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36082725

RESUMO

BACKGROUND: Diabetic nephropathy (DN) is an important and catastrophic complication of diabetes mellitus (DM). Kidney disease has heterogeneity in histology in diabetes patients and includes both diabetic kidney disease (DKD) (albuminuric or nonalbuminuric) and nondiabetic kidney disease (NDKD) either in isolation or in coexistence with DN. Diabetic nephropathy is hard to overturn. While NDKD is treatable and reversible. MATERIALS AND METHODS: We enrolled a total of 50 type 2 diabetes mellitus (T2DM) patients with clinical kidney disease, of both genders and age >18 years, who underwent kidney biopsy from October 2016 to October 2018. Patients with proteinuria <30 mg per day were excluded from the study. The indications of the renal biopsy were nephrotic syndrome (NS), active urinary sediment, rapid decline in renal function, asymptomatic proteinuria, and hematuria. RESULT: A total of 50 (males: 42 and females: eight) patients with T2DM who underwent kidney biopsy were enrolled. The clinical presentation was: NS 26 (52%), chronic kidney disease (CKD) 11 (22%), asymptomatic proteinuria and hematuria six (12%), acute kidney injury (AKI) four (8%), and acute nephritic syndrome (ANS) three (6%). Diabetic retinopathy (DR) was noted in 19 (38%) cases. Kidney biopsy revealed isolated DN, isolated NDKD, and NDKD superimposed on DN in 26 (52%), 14 (28%), and 10 (20%) cases, respectively. Idiopathic membranous nephropathy (MN) (4) and amyloidosis (2) were the most common forms of NDKD, whereas diffuse proliferative glomerulonephritis (DPGN) was the main form of NDKD superimposed on DN. Diabetic nephropathy was observed in 15 (79%) cases in presence of DR and also in 11 (35.5%) cases even in absence of DR. Of eight patients with microalbuminuria four (50%) cases have biopsy-proven DN. CONCLUSION: About 48% of patients had NDKD either in isolation or in coexistence with DN. Diabetic nephropathy was found in absence of DR and in patients with a low level of proteinuria. The level of proteinuria and presence of DR does not help to distinguish DN vs NDKD. Hence, renal biopsy may be useful in selected T2DM patients with clinical kidney disease to diagnose NDKD.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Retinopatia Diabética , Glomerulonefrite , Síndrome Nefrótica , Adolescente , Biópsia , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/diagnóstico , Feminino , Glomerulonefrite/complicações , Hematúria , Humanos , Rim/patologia , Masculino , Síndrome Nefrótica/complicações , Proteinúria/etiologia , Estudos Retrospectivos
4.
J Assoc Physicians India ; 70(9): 11-12, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36082883

RESUMO

The incidence of kidney disease patterns diagnosed by kidney biopsy depends on age, gender, race, socioeconomic, nutritional, and environmental factors. The present study was performed at a tertiary care teaching hospital in central India to show the current frequency of different types of kidney diseases through histopathological findings. MATERIALS AND METHODS: We carried out a retrospective analysis of kidney biopsies done in our institute between January 2016 and June 2021, and clinical and histopathological correlation was done from the available medical records. RESULTS: Of the 411 kidney biopsies evaluated, 56.7% were females and the mean age of patients was 31.65 years. The elderly population (age ≥60 years) constituted 5% of patients. The most common indication for kidney biopsy was nephrotic syndrome (NS) (49.9%). On analysis of histological patterns, 59.3% of patients had primary glomerular disease (PGD), 28% had secondary glomerular disease (SGD), 5.2% had tubulointerstitial disease (TID), and 6.7% had vascular disease. In our study, focal segmental glomerulosclerosis (FSGS) was the most common PGD (28.9% of all PGD) followed by membranous nephropathy (MN) (19.7%), minimal change disease (MCD) (16.5%), and IgA nephropathy (IgAN) (15.4%). The most common SGD was lupus nephritis (LN) (23%) followed by diabetic nephropathy (DN) (1.99%). In patients aged ≤18 years, MCD was the most common PGD (26.5%) and FSGS was the most common PGD (30%) in patients aged between 19 and 59 years. In the elderly population (age ≥60 years), MN was the most common (38%) PGD. CONCLUSION: This is the largest study of kidney biopsies patterns from the central part of India, and it presents the combined analysis of the clinical, histopathological, and immunofluorescent features of biopsy-proven kidney diseases in our population.


Assuntos
Glomerulonefrite por IGA , Glomerulosclerose Segmentar e Focal , Nefropatias , Doenças Vasculares , Adulto , Idoso , Biópsia , Feminino , Glomerulonefrite por IGA/patologia , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/patologia , Humanos , Rim/patologia , Nefropatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doenças Vasculares/patologia , Adulto Jovem
5.
Syst Rev ; 11(1): 197, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36076305

RESUMO

BACKGROUND: Acute kidney injury (AKI) induced by ischemia/reperfusion injury significantly contribute to the burden of end-stage renal disease. Extracellular vesicles (EVs), especially for stem/progenitor cell-derived EVs (stem/progenitor cell-EVs), have emerged as a promising therapy for ischemia/reperfusion injury-induced AKI. However, their regulatory effects remain poorly understood, and their therapeutic efficiency in clinical trials is controversial. Here, we performed this systematic review and meta-analysis to assess the stem/progenitor cell-EV efficacy in treating ischemia/reperfusion injury-induced AKI in preclinical rodent models. METHODS: A literature search was performed in PubMed, Embase, Scopus, and Web of Science to identify controlled studies about the therapeutic efficiency of stem/progenitor cell-EVs on ischemia/reperfusion injury-induced AKI rodent models. The level of SCr, an indicator of renal function, was regarded as the primary outcome. Meta-regression analysis was used to reveal the influential factors of EV therapy. Sensitivity analysis, cumulative meta-analysis, and assessment of publication bias were also performed in our systematic review and meta-analysis. A standardized mean difference (SMD) was used as the common effect size between stem/progenitor cell-EV-treated and control groups, with values of 0.2, 0.5, 0.8, and 1.0 defined as small, medium, large, and very large effect sizes, respectively. RESULTS: A total of 30 studies with 985 ischemia/reperfusion injury-induced AKI rodent models were included. The pooled results showed that EV injection could lead to a remarkable sCr reduction compared with the control group (SMD, - 3.47; 95%CI, - 4.15 to - 2.80; P < 0.001). Meanwhile, the EV treatment group had lower levels of BUN (SMD, - 3.60; 95%CI, - 4.25 to - 2.94; P < 0.001), indexes for tubular and endothelial injury, renal fibrosis (fibrosis score and α-SMA), renal inflammation (TNF-α, IL-1ß, iNOS, and CD68 + macrophages), but higher levels of indexes for tubular proliferation, angiogenesis-related VEGF, and reactive oxygen species. However, our meta-regression analysis did not identify significant associations between sCr level and cell origins of EVs, injection doses, delivery routes, and therapy and outcome measurement time (all P values > 0.05). Significant publication bias was observed (Egger's test, P < 0.001). CONCLUSION: Stem/progenitor cell-EVs are effective in improving renal function in rodent ischemia/reperfusion injury-induced AKI model. These vesicles may help (i) reduce cell apoptosis and stimulate cell proliferation, (ii) ameliorate inflammatory injury and renal fibrosis, (iii) promote angiogenesis, and (iv) inhibit oxidative stress. However, the current systematic review and meta-analysis did not identify significant influential factors associated with treatment effects. More preclinical studies and thoughtfully designed animal studies are needed in the future.


Assuntos
Injúria Renal Aguda , Vesículas Extracelulares , Traumatismo por Reperfusão , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/patologia , Injúria Renal Aguda/terapia , Animais , Modelos Animais de Doenças , Fibrose , Isquemia/patologia , Rim/patologia , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/patologia
7.
Oxid Med Cell Longev ; 2022: 3737137, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092159

RESUMO

Acute renal ischemia/reperfusion (I/R) injury often occurs during kidney transplantation and other kidney surgeries, and the molecular mechanism involves oxidative stress. We hypothesized that ginsenoside Rg1 (Rg1), a saponin derived from ginseng, would protect the renal tissue against acute renal I/R injury by upregulating 5' adenosine monophosphate-activated protein kinase α1 (AMPKα1) expression and inhibiting oxidative stress. The models of acute anoxia/reoxygenation (A/R) damage in normal rat kidney epithelial cell lines (NRK-52E) and acute renal I/R injury in mice were constructed. The results revealed that pretreatment with 25 µM Rg1 significantly increased NRK-52E viability, decreased lactate dehydrogenase (LDH) activity and apoptosis, suppressed reactive oxygen species generation and oxidative stress, stabilized mitochondrial membrane potential and reduced mitochondria permeability transition pore openness, decreased adenosine monophosphate/adenosine triphosphate ratio, and upregulated the expression of AMPKα1, cytochrome b-c1 complex subunit 2, NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 8, and B-cell lymphoma 2, while downregulating BCL2-associated X protein expression. The effects of Rg1 pretreatment were similar to those of pAD/Flag-AMPKα1. After acute renal I/R injury, serum creatinine, blood urea nitrogen, LDH activity, and oxidative stress in renal tissue significantly increased. Rg1 pretreatment upregulated AMPKα1 expression, which protects against acute renal I/R injury by maintaining renal function homeostasis, inhibiting oxidative stress, and reducing apoptosis. Compound C, a specific inhibitor of AMPK, reversed the effects of Rg1. In summary, Rg1 pretreatment upregulated AMPKα1 expression, inhibited oxidative stress, maintained mitochondrial function, improved energy metabolism, reduced apoptosis, and ultimately protected renal tissue against acute renal I/R injury.


Assuntos
Injúria Renal Aguda , Traumatismo por Reperfusão , Injúria Renal Aguda/tratamento farmacológico , Monofosfato de Adenosina , Animais , Ginsenosídeos , Isquemia , Rim/patologia , Rim/fisiologia , Camundongos , Ratos , Reperfusão , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia
8.
BMJ Case Rep ; 15(9)2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109097

RESUMO

A man in his 20s presents to the emergency department after a water skiing accident and was diagnosed with a grade 3 left renal laceration. He subsequently required cystoscopic insertion of a ureteric stent after failing a trial of conservative management. Over the next 9 months, he re-presented to the hospital twice with increasing flank pain and fevers. Subsequent imaging demonstrated interval progression of the retroperitoneal haematoma with a suspicious calcified lower pole lesion which was biopsied subsequently and revealed malignant tissue. External compression of the kidney by this large haematoma was also thought to be contributing to a state of Page kidney. The patient underwent definitive management with an open left-sided radical nephrectomy which confirmed type 2 papillary renal cell carcinoma. The patient is now normotensive and back to his baseline function. He will undergo surveillance CT imaging and be referred to familial genetic services.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/cirurgia , Hematoma/diagnóstico por imagem , Hematoma/etiologia , Hematoma/cirurgia , Humanos , Rim/patologia , Neoplasias Renais/complicações , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Masculino , Nefrectomia
9.
PLoS One ; 17(9): e0268731, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36084046

RESUMO

In immunoglobulin A nephropathy (IgAN), Cox regression analysis can select independent prognostic variables for renal functional decline (RFD). However, the correlation of the selected histological variables with clinical and/or treatment variables is unknown, thereby making histology-based treatment decisions unreliable. We prospectively followed 946 Japanese patients with IgAN for a median of 66 mo. and applied structural equation modeling (SEM) to identify direct and indirect effects of histological variables on RFD as a regression line of estimated glomerular filtration rate (eGFR) via clinical variables including amount of proteinuria, eGFR, mean arterial pressure (MAP) at biopsy, and treatment variables such as steroid therapy with/without tonsillectomy (ST) and renin-angiotensin system blocker (RASB). Multi-layered correlations between the variables and RFD were identified by multivariate linear regression analysis and the model's goodness of fit was confirmed. Only tubular atrophy/interstitial fibrosis (T) had an accelerative direct effect on RFD, while endocapillary hypercellularity and active crescent (C) had an attenuating indirect effect via ST. Segmental sclerosis (S) had an attenuating indirect effect via eGFR and mesangial hypercellularity (M) had accelerative indirect effect for RFD via proteinuria. Moreover, M and C had accelerative indirect effect via proteinuria, which can be controlled by ST. However, both T and S had additional indirect accelerative effects via eGFR or MAP at biopsy, which cannot be controlled by ST. SEM identified a systemic path links between histological variables and RFD via dependent clinical and/or treatment variables. These findings lead to clinically applicable novel methodologies that can contribute to predict treatment outcomes using the Oxford classifications.


Assuntos
Glomerulonefrite por IGA , Biópsia , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/patologia , Humanos , Rim/patologia , Proteinúria/patologia , Estudos Retrospectivos
10.
Eur Rev Med Pharmacol Sci ; 26(17): 6176-6186, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36111917

RESUMO

OBJECTIVE: Approximately 60% of patients with kidney renal clear cell carcinoma (KIRC) die within the first 2-3 years. The prognosis for patients with KIRC and its metastases is poor. Ferroptosis and providing immunity are novel treatment targets for several cancers, including KIRC. Therefore, it is important to identify suitable ferroptosis- and immune-related signatures to predict the prognosis and diagnosis of patients with KIRC. MATERIALS AND METHODS: The corresponding data of patients with KIRC were obtained from the Cancer Genome Atlas. Univariate and multivariate Cox regression analyses were used to screen candidate biomarkers in patients with KIRC. RESULTS: We found that four FI-DEGs (BID, MET, LTB4R, and HMOX1) were independently associated with the overall survival of patients with KIRC. The prognosis and diagnosis model constructed using these four biomarkers could predict the outcome of KIRC, as measured by the receiver operating characteristic analyses. CONCLUSIONS: We identified 4 FI-DEGs that could be used as biomarkers in patients with KIRC. The present study not only contributes to understanding the roles of ferroptosis and immunity in the development of KIRC, but also to the diagnosis and prognosis of KIRC, although it remains to be further studied.


Assuntos
Carcinoma de Células Renais , Ferroptose , Neoplasias Renais , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Humanos , Rim/patologia , Neoplasias Renais/patologia , Nomogramas , Prognóstico
11.
Biomed Pharmacother ; 153: 113407, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076533

RESUMO

Hypertension has become one of the important diseases harmful to human health. In China, Qingda granule (QDG) has been used to treat hypertension for decades. Previous studies by our team have shown that oxidative stress may be one of the pathways through which QDG inhibits hypertension-induced organs injury. However, the specific molecular mechanism of its anti-hypotension and renal oxidative stress response were unclearly. This study investigated QDG's potential protective mechanism against hypertension-induced renal injury. Mice were infused with Angiotensin Ⅱ (Ang Ⅱ, 500 ng/kg/min) or equivalent saline solution (Control) and administered oral QDG (1.145 g/kg/day) or saline for four weeks. QDG treatment mitigated the elevated blood pressure and reduced renal pathological changes induced by Ang Ⅱ. As per the RNA sequencing results, QDG affects oxidative stress signaling. In agreement with these findings, QDG significantly attenuated the Ang Ⅱ-induced increase in Nitrogen oxides 1 (NOX1) and reactive oxygen species and the decrease in superoxide dismutase in renal tissue. Additionally, QDG significantly inhibited Interleukin 6 (IL-6), Tumor necrosis factor α (TNF-α), and Interleukin 1ß (IL-1ß) expression in renal tissues and blocked the phosphorylation of P65 (NF-κB subunit) and IκB. These results were confirmed in vitro. Overall, QDG reduced Ang Ⅱ-induced elevated blood pressure and renal injury by inhibiting oxidative stress and inflammation caused by NOX1 and NF-κB pathways. The results of this study provide an experimental basis for the clinical application of QDG, and to open up a new direction for the clinical treatment of hypertension.


Assuntos
Angiotensina II , Hipertensão , Angiotensina II/efeitos adversos , Angiotensina II/toxicidade , Animais , Medicamentos de Ervas Chinesas , Hipertensão/induzido quimicamente , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Inflamação/metabolismo , Rim/patologia , Camundongos , NF-kappa B/metabolismo , Óxidos de Nitrogênio/metabolismo , Óxidos de Nitrogênio/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos
12.
Oxid Med Cell Longev ; 2022: 7142314, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36082081

RESUMO

Renal ischemia-reperfusion injury (RIRI) is a common pathological process that causes kidney injury. Previous studies have indicated that both peroxisome proliferator-activated receptor γ (PPARγ) and microRNA-21 (miR-21) exert protective effects against RIRI. However, their relationship is not well understood. In the present study, we investigated the role of the PPARγ/miR-21/programmed cell death 4 (PDCD4) axis in IRI, both in vivo and in vitro. In vitro cell hypoxia/reoxygenation (H/R) and in vivo RIRI models were established, and cell viability, cell apoptosis, and key molecule expression profiles were analyzed. Our results showed that both PPARγ and miR-21 had protective effects against RIRI to varying degrees, and there was an interaction between PPARγ and miR-21. PPARγ could promote the expression of miR-21 and partially protect against RIRI by reducing the level of the miR-21 target protein (PDCD4). Our findings underscore the potential utility of future clinical investigations of PPARγ activation and targeting of the underlying miR-21/PDCD4/caspase-3 pathway, which may participate in the pathogenesis of human IRI.


Assuntos
MicroRNAs , PPAR gama , Traumatismo por Reperfusão , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Humanos , Rim/patologia , MicroRNAs/metabolismo , PPAR gama/metabolismo , Proteínas de Ligação a RNA/metabolismo , Traumatismo por Reperfusão/patologia , Transdução de Sinais
13.
Front Immunol ; 13: 950076, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052061

RESUMO

Renal injury secondary to COVID-19 is an important factor for the poor prognosis of COVID-19 patients. The pathogenesis of renal injury caused by aberrant immune inflammatory of COVID-19 remains unclear. In this study, a total of 166 samples from 4 peripheral blood transcriptomic datasets of COVID-19 patients were integrated. By using the weighted gene co-expression network (WGCNA) algorithm, we identified key genes for mild, moderate, and severe COVID-19. Subsequently, taking these genes as input genes, we performed Short Time-series Expression Miner (STEM) analysis in a time consecutive ischemia-reperfusion injury (IRI) -kidney dataset to identify genes associated with renal injury in COVID-19. The results showed that only in severe COVID-19 there exist a small group of genes associated with the progression of renal injury. Gene enrichment analysis revealed that these genes are involved in extensive immune inflammation and cell death-related pathways. A further protein-protein interaction (PPI) network analysis screened 15 PPI-hub genes: ALOX5, CD38, GSF3R, LGR, RPR1, HCK, ITGAX, LYN, MAPK3, NCF4, SELP, SPI1, WAS, TLR2 and TLR4. Single-cell sequencing analysis indicated that PPI-hub genes were mainly distributed in neutrophils, macrophages, and dendritic cells. Intercellular ligand-receptor analysis characterized the activated ligand-receptors between these immune cells and parenchyma cells in depth. And KEGG enrichment analysis revealed that viral protein interaction with cytokine and cytokine receptor, necroptosis, and Toll-like receptor signaling pathway may be potentially essential for immune cell infiltration leading to COVID-19 renal injury. Finally, we validated the expression pattern of PPI-hub genes in an independent data set by random forest. In addition, we found that the high expression of these genes was correlated with a low glomerular filtration rate. Including them as risk genes in lasso regression, we constructed a Nomogram model for predicting severe COVID-19. In conclusion, our study explores the pathogenesis of renal injury promoted by immunoinflammatory in severe COVID-19 and extends the clinical utility of its key genes.


Assuntos
COVID-19 , Biologia Computacional , Biomarcadores Tumorais/genética , COVID-19/genética , Biologia Computacional/métodos , Humanos , Rim/patologia , Ligantes
14.
Front Immunol ; 13: 929244, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059489

RESUMO

Background: Monocytes are involved in the pathogenesis of ANCA-associated vasculitis (AAV). Monocyte/macrophages are the dominant infiltrating cells in the glomeruli of patients with myeloperoxidase-AAV (MPO-AAV). However, how human monocyte subsets extravasate to the kidney in MPO-AAV with renal damage is unclear. Methods: 30 MPO-AAV patients with renal damage and 22 healthy controls were enrolled in this study. Monocyte subsets and monocyte-related chemokines in the blood and kidneys of MPO-AAV patients were detected. The chemoattractant activity of the CX3CL1-CX3CR1 axis on CD16+ monocytes was observed. The effect of MPO-ANCA on the migration of CD16+ monocytes to human glomerular endothelial cells (HGECs) was detected by flow cytometry and transwell migration assay. Results: Compared with controls, CD16+ monocytes were significantly decreased in the blood and increased in the glomeruli of MPO-AAV patients with renal damage. The level of CX3CL1, but not CCL2, was significantly increased in the plasma of MPO-AAV patients. CX3CL1 co-localized with glomerular endothelial cells in MPO-AAV patients with renal damage. Moreover, we initially found that MPO-ANCA promotes an increase of the chemokine CX3CL1 on HGECs, imposing recruitment on CD16+ monocytes. Finally, the percentage of CD16+ monocytes in the blood was found to be positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with urinary protein creatinine ratio in MPO-AAV patients with renal damage. Furthermore, the urinary protein creatinine ratio was positively correlated with the infiltrating of CD14+ and CD16+ cells in the kidneys. Conclusion: Enhanced extravasation of CD16+ monocytes to the kidney via the CX3CL1-CX3CR1 axis may be involved in renal damage in MPO-AAV.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Quimiocina CX3CL1 , Monócitos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/metabolismo , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Anticorpos Anticitoplasma de Neutrófilos/metabolismo , Quimiocina CX3CL1/genética , Quimiocina CX3CL1/metabolismo , Creatinina , Células Endoteliais/metabolismo , Humanos , Rim/metabolismo , Rim/patologia , Monócitos/metabolismo , Peroxidase/efeitos adversos , Peroxidase/metabolismo
15.
Front Immunol ; 13: 901662, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059531

RESUMO

Kidney cancer is one the most lethal cancers of the urinary system, but current treatments are limited and its prognosis is poor. This study focused on kidney renal clear cell carcinoma (KIRC) and analyzed the relationship between epigenetic alterations and KIRC prognosis, and explored the prognostic significance of these findings in KIRC patients. Based on multi-omics data, differentially expressed histone-modified genes were identified using the R package limma package. Gene enhancers were detected from data in the FANTOM5 database. Gene promoters were screened using the R package ChIPseeker, and the Bumphunter in the R package CHAMP was applied to screen differentially methylated regions (DMR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) functional enrichment analysis of genes was performed using the R package clusterProfiler. We identified 51 dysregulated epigenetic protein coding genes (epi-PCGs) from 872 epi-PCGs, and categorized three molecular subtypes (C1, C2, and C3) of KIRC samples with significantly different prognosis. Notably, among the three molecular subtypes, we found a markedly differential immune features in immune checkpoints, cytokines, immune signatures, and immune cell distribution. C2 subtype had significantly lower enrichment score of IFNγ, cytotoxic score (CYT), and angiogenesis. In addition, an 8-gene signature containing 8 epi-PCGs (ETV4, SH2B3, FATE1, GRK5, MALL, HRH2, SEMA3G, and SLC10A6) was developed for predicting KIRC prognosis. Prognosis of patients with a high 8-gene signature score was significantly worse than those with a low 8-gene signature score, which was also validated by the independent validation data. The 8-gene signature had a better performance compared with previous signatures of KIRC. Overall, this study highlighted the important role of epigenetic regulation in KIRC development, and explored prognostic epi-PCGs, which may provide a guidance for exploiting further pathological mechanisms of KIRC and for developing novel drug targets.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Transportadores de Ânions Orgânicos , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/patologia , Proteínas de Ligação a DNA/genética , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Marcadores Genéticos , Genômica , Humanos , Rim/patologia , Neoplasias Renais/patologia , Transportadores de Ânions Orgânicos/genética , Transportadores de Ânions Orgânicos/metabolismo , Fatores de Transcrição/metabolismo
16.
Eur J Med Res ; 27(1): 176, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36088368

RESUMO

Hyperuricemia can induce acute and chronic kidney damage, but the pathological mechanism remains unclear. The potential role of AMP-activated protein kinase (AMPK) α2 in hyperuricemia-induced renal injury was investigated in this study. Acute and chronic hyperuricemic nephropathy was induced by administering intraperitoneal injections of uric acid and oxonic acid to AMPK α2 knockout and wild-type mice. Changes in renal function, histopathology, inflammatory cell infiltration, renal interstitial fibrosis, and urate deposition were analyzed. In both acute and chronic hyperuricemic nephropathy mouse models, knockout of AMPK α2 significantly reduced serum creatinine levels and renal pathological changes. The tubular expression of kidney injury molecule-1 was also reduced in hyperuricemic nephropathy mice deficient in AMPK α2. In addition, knockout of AMPK α2 significantly suppressed the infiltration of renal macrophages and progression of renal interstitial fibrosis in mice with chronic hyperuricemic nephropathy. Knockout of AMPK α2 reduced renal urate crystal deposition, probably through increasing the expression of the uric acid transporter, multidrug resistance protein 4. In summary, AMPK α2 is involved in acute and chronic hyperuricemia-induced kidney injury and may be associated with increased urate crystal deposition in the kidney.


Assuntos
Hiperuricemia , Nefropatias , Falência Renal Crônica , Proteínas Quinases Ativadas por AMP/genética , Animais , Modelos Animais de Doenças , Fibrose , Hiperuricemia/induzido quimicamente , Hiperuricemia/genética , Rim/patologia , Nefropatias/genética , Nefropatias/metabolismo , Camundongos , Camundongos Knockout , Ácido Úrico/efeitos adversos , Ácido Úrico/metabolismo
17.
Turk J Pediatr ; 64(4): 759-765, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36082651

RESUMO

BACKGROUND: Childhood hypertension is getting more attention in recent years. We present a case report of a rare cause of secondary arterial hypertension in a teenage girl - a solitary fibrous tumor of the kidney. The case demonstrates that standard imaging techniques, computed tomography and magnetic resonance imaging, are not fully reliable in the diagnosis of renovascular hypertension. CASE: A 15-year old girl was admitted to the Pediatric Department because of episodes of stiffness in the limbs, accompanied by pale skin and lips, dated 4 months back. During these episodes, high blood pressure up to 160/100 mmHg was measured. A 24-hour blood pressure monitoring demonstrated arterial hypertension stage II. Renovascular hypertension was suspected, but the computed tomography examination of the abdomen showed normal-sized renal arteries. In the left kidney hilum, an intraparenchymal formation was discovered. The data presented a non-specific lesion with a wide differential diagnosis. Given the fact that the patient had been treated with an ACE-inhibitor, serum renin level could not be correctly interpreted. The lesion was removed through a laparoscopic intervention. Intraoperatively, the tumor was compressing a small intra-renal vessel - a finding that hadn`t been discovered by the previous imaging studies. The final pathologist diagnosis was: solitary fibrous tumor. During the next six months of follow-up, the maximal blood pressure values of the patient were up to 120/80 mmHg. CONCLUSIONS: Solitary fibrous tumors of the kidneys are infrequent in children. The presented case displays a rare form of initial clinical manifestation of this tumor. It is also a demonstration that standard imaging techniques are not able to get a precise visualization of the small intra-renal vessels. At the same time, the decision of whether or not to perform a more invasive procedure should be based on the clinical conditions and risks of the individual patient.


Assuntos
Hipertensão Renovascular , Hipertensão , Neoplasias Renais , Tumores Fibrosos Solitários , Adolescente , Criança , Feminino , Humanos , Hipertensão/etiologia , Hipertensão Renovascular/diagnóstico , Hipertensão Renovascular/etiologia , Rim/patologia , Neoplasias Renais/complicações , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Tumores Fibrosos Solitários/complicações , Tumores Fibrosos Solitários/diagnóstico por imagem , Tumores Fibrosos Solitários/cirurgia
18.
Turk J Pediatr ; 64(4): 781-786, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36082654

RESUMO

BACKGROUND: Amyloidosis is a group of disorders with extracellular accumulation of autologous fibrillary insoluble proteins in various tissues and organs such as the kidneys, liver, spleen, heart and gastrointestinal tract leading to impairment of normal organ function. Childhood amyloidosis is an exceedingly rare entity mainly caused by familial Mediterranean fever (FMF) and the other autoinflammatory diseases such as mevalonate kinase deficiency (MKD). CASE: A 16-year-old male was referred to pediatric nephrology for coincidentally discovered proteinuria. He had no significant findings on physical examination except for urochromic color. He had nephrotic range proteinuria with 109 mg/m2/h and serum creatinine was 1.35 mg/dl. Kidney biopsy was performed because of nephrotic range proteinuria with acute kidney injury. In hematoxylin-eosin-stained tissue sections, amyloid was suggested as extracellular amorphous material that is lightly eosinophilic in the glomeruli. Diagnosis was confirmed by Congo red positivity, with apple-green birefringence under polarized light. MEFV gene mutation was negative and a compound heterozygote mutation found in mevalonate kinase gene. A 6-monthtrial of colchicine, enalapril, and losartan combination was not successful; Canakinumab was started thereafter. Proteinuria and creatinine decreased to 7 mg/m2/h and 0.6 mg/dl respectively 4 years after treatment. CONCLUSIONS: Amyloidosis should be considered especially in children presenting with proteinuria and with a history of recurrent fever. This report also emphasizes the efficacy of canakinumab to prevent or decelerate chronic renal failure in these patients although it does not reduce tissue deposition in long-term use.


Assuntos
Injúria Renal Aguda , Amiloidose , Febre Familiar do Mediterrâneo , Adolescente , Amiloidose/complicações , Amiloidose/diagnóstico , Criança , Febre Familiar do Mediterrâneo/complicações , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Humanos , Rim/patologia , Masculino , Proteinúria/etiologia , Pirina/genética , Proteína Amiloide A Sérica
20.
BMJ Case Rep ; 15(9)2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36100289

RESUMO

Renal malakoplakia, a seldom seen chronic inflammatory condition, continues to elude medical, surgical, radiological and pathological specialists due to its mimicry of other renal pathologies and low incidence. The variable clinical manifestations and non-specific radiological findings of malakoplakia can be misleading, and ultimately require a pathological diagnosis. A literature review reveals an extremely low prevalence of renal malakoplakia, a handful of invasive renal malakoplakia cases and no reports of liver and diaphragmatic invasion. We present a case of a renal mass with liver and diaphragmatic invasion in a 59-year-old woman that deceived clinicians and radiologists until a pathological diagnosis of renal malakoplakia was performed. This case highlights the need of awareness for malakoplakia in the differential diagnosis for renal invasive and non-invasive masses. The need to await a surgical biopsy and pathological diagnosis is critical to ensure a correct diagnosis and avoid unnecessary surgery of the kidney.


Assuntos
Transplante de Rim , Malacoplasia , Diafragma/diagnóstico por imagem , Diafragma/patologia , Feminino , Humanos , Rim/diagnóstico por imagem , Rim/patologia , Transplante de Rim/efeitos adversos , Fígado/diagnóstico por imagem , Fígado/patologia , Malacoplasia/diagnóstico , Malacoplasia/patologia , Pessoa de Meia-Idade
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