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1.
Methods Mol Biol ; 2259: 105-141, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33687711

RESUMO

Identification of molecular biomarkers for human diseases is one of the most important disciplines in translational science as it helps to elucidate their origin and early progression. Thus, it is a key factor in better diagnosis, prognosis, and treatment. Proteomics can help to solve the problem of sample complexity when the most common primary sample specimens were analyzed: organic fluids of easy access. The latest developments in high-throughput and label-free quantitative proteomics (SWATH-MS), together with more advanced liquid chromatography, have enabled the analysis of large sample sets with the sensitivity and depth needed to succeed in this task. In this chapter, we show different sample processing methods (major protein depletion, digestion, etc.) and a micro LC-SWATH-MS protocol to identify/quantify several proteins in different types of samples (serum/plasma, saliva, urine, tears).


Assuntos
Proteínas/análise , Proteoma/análise , Proteômica/métodos , Biomarcadores/análise , Biomarcadores/sangue , Biomarcadores/urina , Proteínas Sanguíneas/análise , Humanos , Espectrometria de Massas/métodos , Proteinúria/diagnóstico , Saliva/química , Manejo de Espécimes/métodos , Lágrimas/química
2.
Methods Mol Biol ; 2292: 3-15, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33651347

RESUMO

Recent reports suggest that urine is a useful noninvasive tool for the identification of urogenital tumors, including bladder, prostate, kidney, and other nonurological cancers. As a liquid biopsy, urine represents an important source for the improvement of new promising biomarkers, a suitable tool to identify indolent cancer and avoid overtreatment. Urine is enriched with DNAs, RNAs, proteins, circulating tumor cells, exosomes, and other small molecules which can be detected with several diagnostic methodologies.We provide an overview of the ongoing state of urinary biomarkers underlying both their potential utilities to improve cancer prognosis, diagnosis, and therapeutic strategy and their limitations.


Assuntos
Biomarcadores Tumorais/urina , Neoplasias/urina , Animais , Ácidos Nucleicos Livres/urina , Exossomos/patologia , Humanos , Biópsia Líquida/métodos , Neoplasias/diagnóstico , Neoplasias/patologia , Ácidos Nucleicos/urina , Proteínas , Proteinúria/diagnóstico , Proteinúria/patologia , Proteinúria/urina , Urinálise/métodos
3.
Methods Mol Biol ; 2292: 115-120, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33651356

RESUMO

The analysis of liquid biopsy as a source of diagnostic, prognostic, and predictive biomarkers is still object of the main research in the prostate cancer field. Many advantages, such as less invasiveness compared to plasma or serum analysis and the rich content, confer to urine a role as an interesting fluid to be analysed especially in urological diseases. Here we report a workflow focused on profile, concentration, and protein surface characterization of EVs from urinary supernatant.


Assuntos
Exossomos/patologia , Neoplasias da Próstata/diagnóstico , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/urina , Humanos , Biópsia Líquida/métodos , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/urina , Proteínas/análise , Proteinúria/diagnóstico , Proteinúria/patologia , Proteinúria/urina , Coleta de Urina/métodos , Fluxo de Trabalho
4.
Methods Mol Biol ; 2292: 143-150, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33651359

RESUMO

Advances in mass spectrometry instrumentation have revolutionized analytical capability in clinical proteomics. In parallel, various sample preparation methods have been developed to try to address the inherent complexity and dynamic range of clinical samples, typically involving a combination of depletion of abundant proteins followed by extensive prefractionation. However, the depth of coverage routinely achieved in discovery proteomics experiments on peripheral fluids such as serum, still leaves something to be desired, especially if no depletion or prefractionation is done in order to increase the throughput of clinical samples. Remarkably, despite being an easily accessible, typically sterile and diagnostically rich clinical sample, urine is often overlooked and as such has received less development effort. As an ultrafiltrate of blood, urine contains proteins and protein fragments originating from all parts of the body which may have diagnostic or prognostic potential if accurately and reproducibly quantified. Here, we describe an efficient and simple method for the concentration of urine samples by methanol-chloroform precipitation and subsequent in-solution tryptic digestion prior to discovery or targeted mass spectrometry analysis. We exemplify this method by reference to the discovery of novel candidate urinary biomarkers of schistosomiasis. Importantly, the methods described here have been used to identify >1900 protein groups in human urine by label-free discovery proteomics, without requiring any prior depletion or prefractionation, making this approach amenable to high throughput clinical biomarker studies in many diseases.


Assuntos
Proteinúria/urina , Proteômica/métodos , Esquistossomose/urina , Espectrometria de Massas em Tandem/métodos , Neoplasias da Bexiga Urinária/urina , Animais , Biomarcadores Tumorais/urina , Humanos , Proteinúria/parasitologia , Schistosoma/isolamento & purificação , Esquistossomose/parasitologia , Neoplasias da Bexiga Urinária/parasitologia
5.
Ren Fail ; 43(1): 335-339, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33567947

RESUMO

The introduction of Bruton's tyrosine kinase inhibitor ibrutinib has made a significant progress in the treatment of chronic lymphocytic leukemia and other B-cell malignancies. Due to the reduction of cytokine release, it is effective in chronic graft-versus-host disease, and its use has also been suggested in autoimmune diseases and in prevention of COVID-19-associated lung damage. Despite this effect on the immune response, we report a severe hypersensitivity reaction in a 76-year-old male patient diagnosed with prolymphocytic leukemia. Four weeks after the ibrutinib start, non-oliguric acute kidney injury with proteinuria and microscopic hematuria developed and that was accompanied by lower limb purpuras and paresthesia. Renal biopsy revealed acute interstitial nephritis. Employing 1 mg/kg methylprednisolone administration, serum creatinine decreased from 365 µmol/L to 125 µmol/L at 11 days and the proteinuria-hematuria as well as the purpura, paresthesia resolved. Three months later at stabile eGFR of 56 ml/min/1.73 m2 methylprednisolone was withdrawn and a rituximab-venetoclax treatment was initiated without side effects. We conclude that despite the beneficial effect on cytokines response in Th1 direction, ibrutinib can cause acute interstitial nephritis. Early detection, discontinuation of ibrutinib, glucocorticoid administration may help to better preserve renal function, thereby lowering the risk of potential subsequent kidney injury.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Adenina/análogos & derivados , Nefrite Intersticial/induzido quimicamente , Piperidinas/efeitos adversos , Proteinúria/induzido quimicamente , Lesão Renal Aguda/tratamento farmacológico , Adenina/efeitos adversos , Idoso , Citocinas/efeitos dos fármacos , Glucocorticoides/uso terapêutico , Humanos , Rim/patologia , Leucemia Prolinfocítica/tratamento farmacológico , Masculino , Nefrite Intersticial/tratamento farmacológico , Inibidores de Proteínas Quinases , Proteinúria/tratamento farmacológico
6.
Methods Mol Biol ; 2224: 123-132, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33606211

RESUMO

Proteinuria is a widely used marker of renal disease and is strongly associated with renal and cardiovascular outcomes. The molecular mechanisms underlying filtration of serum proteins through the glomerular filtration barrier (GFB) remain to be determined. Since the GFB is a complex structure, studies of albumin or IgG trafficking in cultured cells in vitro may not fully recapitulate these processes in vivo. In other epithelial cells including renal proximal tubular cells, the neonatal Fc receptor (FcRn) is required to divert albumin and IgG from the degradative pathway which allows these proteins to be recycled or transcytosed. To examine the role of podocyte FcRn in albumin and IgG trafficking in vivo, we detail the creation of a podocyte-specific FcRn knockout mouse and describe methods for examining intraglomerular detection of albumin and IgG in these mice.


Assuntos
Antígenos de Histocompatibilidade Classe I/metabolismo , Podócitos/metabolismo , Receptores Fc/metabolismo , Albuminas/metabolismo , Animais , Células Epiteliais/metabolismo , Feminino , Imunoglobulina G/metabolismo , Túbulos Renais Proximais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transporte Proteico/fisiologia , Proteinúria/metabolismo , Transcitose/fisiologia
7.
J Diabetes Res ; 2021: 6666086, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33506050

RESUMO

Background: The risk factors for acute kidney injury (AKI) development in patients with diabetes hospitalized for COVID-19 have not been fully studied yet. In this study, we aimed to estimate the rate of AKI among the hospitalized population with COVID-19 and to identify the risk factors associated with AKI among patients with diabetes. Material and Methods. This retrospective cohort study included 254 patients (127 with diabetes and 127 without diabetes) who were admitted for COVID-19 to a tertiary hospital in Tehran, Iran, between February and May 2020. Clinical characteristics and outcomes, radiological findings, and laboratory data, including data on AKI, hematuria, and proteinuria were recorded and analyzed. Results: Of 254 patients, 142 (55.9%) were male and the mean (± SD) age was 65.7 years (±12.5). In total, 58 patients (22.8%) developed AKI during hospitalization, of whom 36 patients had diabetes (p = 0.04); most patients (74.1%) had stage 1 or 2 AKI. Also, 8 patients (13.8%) required renal replacement therapy (RRT) after developing AKI. Regardless of diabetes status, patients who developed AKI had significantly higher mortality rates compared with patients who did not develop AKI (p = 0.02). Hematuria and proteinuria were observed in 38.1% and 55% of patients, respectively. Multivariate analysis showed that invasive mechanical ventilation, proteinuria, HBA1c level, history of cardiovascular disease, and use of statins were independent risk factors for AKI development in patients with diabetes. Conclusion: Results of this study showed that AKI develops in a considerable percentage of patients with COVID-19, especially in those with diabetes, and is significantly associated with mortality.


Assuntos
Lesão Renal Aguda/epidemiologia , /epidemiologia , Complicações do Diabetes/epidemiologia , Diabetes Mellitus/epidemiologia , Idoso , Doenças Cardiovasculares/complicações , Feminino , Hemoglobina A Glicada/análise , Hematúria/epidemiologia , Mortalidade Hospitalar , Hospitalização , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Proteinúria/epidemiologia , Terapia de Substituição Renal/efeitos adversos , Respiração Artificial , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Resultado do Tratamento
8.
J Diabetes Res ; 2021: 7830136, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33506052

RESUMO

Backgrounds: Diabetes mellitus (DM) is one of the most common comorbidities in patients with coronavirus disease (COVID-19). We aim to summarize the clinical features of DM patients with COVID-19 and find out potential factors associated with severe disease. Methods: In this retrospective, single-center study, the medical records of patients with COVID-19 in Changsha, Hunan, China, from January 21, 2020, to February 19, 2020, were reviewed. Epidemiological information, clinical features, and outcomes were compared between DM patients admitted to the intensive care unit (ICU) or not. Results: A total of 241 patients confirmed with COVID-19 were enrolled, including 19 DM patients. There were more patients in DM group admitted to the ICU than non-DM group (36.8% vs. 15.8%, P = 0.045). Compared with non-DM group in the ICU, there were more female patients from DM group in the ICU (85.7% vs. 31.4%, P = 0.024). On admission, the mean level of glycated hemoglobin A1c (HbA1c) was higher in the ICU DM patients than that in the non-ICU DM patients (8.5% vs. 7.1%). There were more DM patients with proteinuria in the ICU group than the non-ICU group (57.1% vs. 33.3%). Twelve DM patients (63.2%) changed diabetic therapy during hospitalization, and all DM patients admitted to the ICU used insulin. As of March 14, all 19 DM patients have been discharged, and no death occurred. Conclusions: DM patients with COVID-19 are vulnerable to severe disease, especially for female patients. High levels of HbA1c and proteinuria could be potential risk factors for severe COVID-19 in DM patients. In addition to timely systemic therapy, the control of blood glucose and proper diabetic therapy is essential to improve the prognosis of severe DM patients with COVID-19.


Assuntos
/complicações , Complicações do Diabetes/epidemiologia , Diabetes Mellitus/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/análise , Criança , Pré-Escolar , China , Cuidados Críticos , Feminino , Hemoglobina A Glicada/análise , Hospitalização , Humanos , Lactente , Unidades de Terapia Intensiva , Masculino , Registros Médicos , Pessoa de Meia-Idade , Proteinúria , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
9.
Kidney Int ; 99(1): 20-22, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33390228

RESUMO

Activation of cellular antioxidative signaling is expected to be a silver bullet against kidney diseases, and clinical trials of compounds activating the antioxidant transcription factor Nrf2 have revealed their renoprotective effects. However, cardiac events have been observed in some cases with elevated urinary albumin excretion in these trials. Therefore, elucidating the negative effects of Nrf2 activation is essential. Rush and colleagues demonstrated that Nrf2 activation aggravates podocyte injury, a factor related to proteinuria and cardiac failure.


Assuntos
Podócitos , Insuficiência Renal Crônica , Animais , Antioxidantes/uso terapêutico , Camundongos , Fator 2 Relacionado a NF-E2/genética , Proteinúria
10.
West Afr J Med ; 38(1): 8-14, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33463700

RESUMO

BACKGROUND: Urinary abnormalities detected on routine urinalysis in asymptomatic children may be indicators of underlying kidney diseases. OBJECTIVE: This study was conducted to determine the prevalence and risk factors for asymptomatic proteinuria and haematuria in healthy primary school children in Abuja. METHODS: Using multi-staged sampling method, early morning mid-stream urine was collected from healthy school children from urban and rural primary schools in Gwagwalada Area Council of Abuja, Nigeria for the presence of proteinuria and haematuria using urinalysis strips. Those positive for proteinuria and haematuria were retested after two weeks for persistence abnormalities. Urine microscopy was also done for the persistent haematuria subjects, and biodata collected. RESULTS: Of 861 urine samples analysed, 215 (25%) were from urban schools, and 646 (75%) from rural schools. There were 397 (46.1%) males. Their mean age was 9.5±2.1 years (range 6-12 years), with 9-10 years accounting for 36.4% of the study population. Proteinuria, haematuria, proteinuria+haematuria, persistent proteinuria, and persistent haematuria were seen in 7.0%, 10.6%, 3.6%, 4.2% and 5.5% of the subjects respectively. Microscopic haematuria was also documented in 5.2% subjects with persistent haematuria. Statistical significant association was seen between proteinuria with location of school (c2=9.529, p=0.002), and social class (c2=7.596, p=0.022). Significant association was also seen between haematuria and location of school (c2=14.218, p=0.001), social class (c2=11.290, p = 0.004). CONCLUSION: There was high prevalence of asymptomatic proteinuria and haematuria among healthy primary school children from the study area. This underscores the importance of routine urinary screening program in primary schools for early identification of affected children for intervention.


Assuntos
Hematúria , Microscopia , Proteinúria , Criança , Feminino , Hematúria/diagnóstico , Hematúria/epidemiologia , Humanos , Masculino , Nigéria/epidemiologia , Prevalência , Proteinúria/diagnóstico , Proteinúria/epidemiologia , Instituições Acadêmicas , Urinálise
11.
BMC Infect Dis ; 21(1): 124, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33509123

RESUMO

BACKGROUND: Kidney involvement of visceral Leishmaniasis is previously reported, but knowledge is limited. Hypergammaglobulinemia is common in visceral leishmaniasis patients. Whether hypergammaglobulinemia after leishmaniasis depletion can cause kidney injury is not well reported yet. CASE PRESENTATION: We reported a patient who recovered from visceral Leishmaniasis but showed persistent hypergammaglobulinemia and elevated urinary protein. Kidney biopsy showed glomerular hypertrophy with mild segmental mesangial proliferation without tubulointerstitial involvement in light microscopy. No immune complex deposit was found in the mesangial area by neither immunofluorescent staining nor electronic microscope. Increased lysosomes were observed in proximal tubules by electronic microscope. Valsartan was administered to decrease urinary protein, and no immune-suppressive therapy was added. The urinary protein and serum IgG level gradually dropped, and serum creatinine level remained stable during three- month follow up. CONCLUSIONS: Hypergammaglobulinemia is unlikely to cause renal structural or functional damage in the short term. Angiotensin blockade significantly reduced urine protein, with a minor effect on IgG elimination.


Assuntos
Hipergamaglobulinemia/etiologia , Leishmaniose Visceral/complicações , Proteinúria/etiologia , Adulto , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Humanos , Hipergamaglobulinemia/tratamento farmacológico , Hipergamaglobulinemia/patologia , Rim/patologia , Masculino , Proteinúria/tratamento farmacológico , Proteinúria/patologia , Resultado do Tratamento , Valsartana/uso terapêutico
12.
BMJ Case Rep ; 14(1)2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514619

RESUMO

We report the case of a 43-year-old man, suffering from ankylosing spondylitis and treated with Infliximab 5 mg/kg every 2 months, with an excellent disease control. During a follow-up consultation, an incipient renal insufficiency is detected. A urine analysis showed haematuria and proteinuria and a renal puncture-biopsy revealed an image of IgA nephropathy.Several cases of IgA nephropathy have been reported in the literature associated with ankylosing spondylitis. Some of them occur in patients treated with antitumour necrosis factor, but it is unclear whether this pathology is caused by the treatment or whether treatment failed to prevent its occurrence.Our clinical case highlights the importance of regular monitoring of renal function in patients with ankylosing spondylitis, as well as urinary spotting.The question of whether the disease itself, the treatment or other factors such as immune dysregulation could be held responsible for kidney disease will be addressed in the discussion.


Assuntos
Antirreumáticos/uso terapêutico , Glomerulonefrite por IGA/patologia , Infliximab/uso terapêutico , Espondilite Anquilosante/complicações , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Antirreumáticos/administração & dosagem , Biópsia , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/urina , Hematúria/diagnóstico , Humanos , Infliximab/administração & dosagem , Rim/patologia , Testes de Função Renal/normas , Masculino , Monitorização Fisiológica/normas , Proteinúria/diagnóstico , Remissão Espontânea , Espondilite Anquilosante/tratamento farmacológico
13.
Methods Mol Biol ; 2225: 241-255, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33108667

RESUMO

Systemic lupus erythematosus (SLE) is a multifactorial and heterogeneous autoimmune disease involving multiple organ systems and tissues. Lupus nephritis occurs in approximately 60% of patients with SLE and is the leading cause of morbidity. Diffuse alveolar hemorrhage (DAH) is a rare but very serious complication of SLE with a greater than 50% associated mortality. The etiology of SLE is unclear but has proposed genetic, hormonal, and environmental aspects. Pristane is a saturated terpenoid alkane and has become the most popular laboratory model for inducing lupus in mice. The pristane model of SLE has the capacity to reproduce many components of the human presentation of the disease. Previous studies have demonstrated that virus-derived immune-modulating proteins have the potential to control inflammatory and autoimmune disorders. Serp-1, a 55 kDa secreted and highly glycosylated immune modulator derived from myxoma virus (MYXV), has potent immunomodulatory activity in models of vasculitis, viral sepsis, collagen-induced arthritis, and transplant rejection. This chapter describes the mouse preclinical pristane lupus model as a method to examine virus-derived protein efficacy for treating autoimmune diseases and specifically lupus nephritis and DAH.


Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Hemorragia/prevenção & controle , Fatores Imunológicos/farmacologia , Nefrite Lúpica/tratamento farmacológico , Myxoma virus/química , Proteinúria/tratamento farmacológico , Proteínas Virais/farmacologia , Animais , Autoanticorpos/biossíntese , Citocinas/biossíntese , Modelos Animais de Doenças , Feminino , Hemorragia/imunologia , Hemorragia/patologia , Humanos , Fatores Imunológicos/imunologia , Injeções Intraperitoneais , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Pulmão/patologia , Nefrite Lúpica/induzido quimicamente , Nefrite Lúpica/imunologia , Nefrite Lúpica/patologia , Camundongos , Camundongos Endogâmicos BALB C , Proteinúria/induzido quimicamente , Proteinúria/imunologia , Proteinúria/patologia , Terpenos/administração & dosagem , Resultado do Tratamento , Proteínas Virais/imunologia
14.
Am J Physiol Renal Physiol ; 320(3): F285-F296, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33346727

RESUMO

This study investigated the molecular mechanisms underlying the antiproteinuric effect of DPP4 inhibition in 5/6 renal ablation rats and tested the hypothesis that the urinary activity of DPP4 correlates with chronic kidney disease (CKD) progression. Experiments were conducted in male Wistar rats who underwent 5/6 nephrectomy (Nx) or sham operation followed by 8 wk of treatment with the DPP4 inhibitor (DPP4i) sitagliptin or vehicle. Proteinuria increased progressively in Nx rats throughout the observation period. This increase was remarkably mitigated by sitagliptin. Higher levels of proteinuria in Nx rats compared to control rats were accompanied by higher urinary excretion of retinol-binding protein 4, a marker of tubular proteinuria, as well as higher urinary levels of podocin, a marker of glomerular proteinuria. Retinol-binding protein 4 and podocin were not detected in the urine of Nx + DPP4i rats. Tubular and glomerular proteinuria was associated with the reduced expression of megalin and podocin in the renal cortex of Nx rats. Sitagliptin treatment partially prevented this decrease. Besides, the angiotensin II renal content was significantly reduced in the Nx rats that received sitagliptin compared to vehicle-treated Nx rats. Interestingly, both urinary DPP4 activity and abundance increased progressively in Nx rats. Additionally, urinary DPP4 activity correlated positively with serum creatinine levels, proteinuria, and blood pressure. Collectively, these results suggest that DPP4 inhibition ameliorated both tubular and glomerular proteinuria and prevented the reduction of megalin and podocin expression in CKD rats. Furthermore, these findings suggest that urinary DPP4 activity may serve as a biomarker of renal disease and progression.


Assuntos
Dipeptidil Peptidase 4/urina , Inibidores da Dipeptidil Peptidase IV/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Rim/efeitos dos fármacos , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Proteínas de Membrana/metabolismo , Proteinúria/prevenção & controle , Insuficiência Renal Crônica/prevenção & controle , Fosfato de Sitagliptina/farmacologia , Angiotensina II/metabolismo , Animais , Biomarcadores/urina , Modelos Animais de Doenças , Fibrose , Rim/enzimologia , Rim/patologia , Masculino , Proteinúria/enzimologia , Proteinúria/patologia , Proteinúria/urina , Ratos Wistar , Insuficiência Renal Crônica/enzimologia , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/urina , Proteínas Plasmáticas de Ligação ao Retinol/urina , Transdução de Sinais
15.
Am J Physiol Renal Physiol ; 320(1): F97-F113, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33308016

RESUMO

We recently reported that the enhanced susceptibility to chronic kidney disease (CKD) in the fawn-hooded hypertensive (FHH) rat is caused, at least in part, by a mutation in γ-adducin (ADD3) that attenuates renal vascular function. The present study explored whether Add3 contributes to the modulation of podocyte structure and function using FHH and FHH.Add3 transgenic rats. The expression of ADD3 on the membrane of primary podocytes isolated from FHH was reduced compared with FHH.Add3 transgenic rats. We found that F-actin nets, which are typically localized in the lamellipodia, replaced unbranched stress fibers in conditionally immortalized mouse podocytes transfected with Add3 Dicer-substrate short interfering RNA (DsiRNA) and primary podocytes isolated from FHH rats. There were increased F/G-actin ratios and expression of the Arp2/3 complexes throughout FHH podocytes in association with reduced synaptopodin and RhoA but enhanced Rac1 and CDC42 expression in the renal cortex, glomeruli, and podocytes of FHH rats. The expression of nephrin at the slit diaphragm and the levels of focal adhesion proteins integrin-α3 and integrin-ß1 were decreased in the glomeruli of FHH rats. Cell migration was enhanced and adhesion was reduced in podocytes of FHH rats as well as in immortalized mouse podocytes transfected with Add3 DsiRNA. Mean arterial pressures were similar in FHH and FHH.Add3 transgenic rats at 16 wk of age; however, FHH rats exhibited enhanced proteinuria associated with podocyte foot process effacement. These results demonstrate that reduced ADD3 function in FHH rats alters baseline podocyte pathophysiology by rearrangement of the actin cytoskeleton at the onset of proteinuria in young animals.


Assuntos
Citoesqueleto de Actina/metabolismo , Proteínas de Ligação a Calmodulina/metabolismo , Hipertensão/metabolismo , Podócitos/metabolismo , Proteinúria/metabolismo , Insuficiência Renal Crônica/metabolismo , Citoesqueleto de Actina/patologia , Animais , Pressão Arterial , Proteínas de Ligação a Calmodulina/genética , Adesão Celular , Linhagem Celular , Movimento Celular , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Adesões Focais/metabolismo , Adesões Focais/patologia , Hipertensão/genética , Hipertensão/patologia , Hipertensão/fisiopatologia , Integrinas/metabolismo , Masculino , Camundongos , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Podócitos/patologia , Proteinúria/genética , Proteinúria/patologia , Proteinúria/fisiopatologia , Ratos Endogâmicos , Ratos Transgênicos , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/fisiopatologia , Transdução de Sinais
16.
Biomed Pharmacother ; 133: 111061, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378964

RESUMO

QiDiTangShen granules (QDTS), a traditional Chinese herbal medicine, have been used in clinical practice for treating diabetic kidney disease for several years. In our previous study, we have demonstrated that QDTS displayed good efficacy on reducing proteinuria in mice with diabetic nephropathy (DN). However, the exact mechanism by which QDTS exerts its reno-protection remains largely unknown. To ascertain whether QDTS could target the gut microbiota-bile acid axis, the db/db mice were adopted as a mouse model of DN. After a 12-week of treatment, we found that QDTS significantly reduced urinary albumin excretion (UAE), and attenuated the pathological injuries of kidney in the db/db mice, while the body weight and blood glucose levels of those mice were not affected. In addition, we found that QDTS significantly altered the gut microbiota composition, and decreased serum levels of total bile acid (TBA) and BA profiles such as ß-muricholic acid (ß-MCA), taurocholic acid (TCA), tauro ß-muricholic acid (Tß-MCA) and deoxycholic acid (DCA). These BAs are associated with the activation of farnesoid X receptor (FXR), which is highly expressed in kidney. However, there was no significant difference between QDTS-treated and -untreated db/db mice regarding the renal expression of FXR, indicating that other mechanisms may be involved. Conclusively, our study revealed that QDTS significantly alleviated renal injuries in mice with DN. The gut microbiota-bile acid axis may be an important target for the reno-protection of QDTS in DN, but the specific mechanism merits further study.


Assuntos
Ácidos e Sais Biliares/sangue , Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Rim/efeitos dos fármacos , Animais , Biomarcadores/sangue , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/microbiologia , Nefropatias Diabéticas/patologia , Modelos Animais de Doenças , Disbiose , Fezes/microbiologia , Intestinos/microbiologia , Intestinos/patologia , Rim/metabolismo , Rim/ultraestrutura , Masculino , Proteinúria/sangue , Proteinúria/microbiologia , Proteinúria/prevenção & controle
17.
Diabetes Metab Syndr ; 15(1): 187-191, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33383438

RESUMO

BACKGROUND AND AIMS: Renal involvement in Covid-19 infection is varied and can affect glomeruli, tubules, interstitium and can cause acute kidney injury (AKI). AKI is a strong predictor of mortality. Routine urinalysis gives an insight into the renal pathology of the patient. We studied the incidence of urinary abnormalities in hospitalised Covid-19 patients and analysed their impact on development of AKI and mortality. METHODS: Information on 110 hospitalised patients with confirmed Covid-19 was retrospectively collected and analysed. The demographic data such as age, gender, comorbid conditions such as diabetes mellitus, the need for dialysis and laboratory data such as urine for albumin, glucose, RBC and WBC, and serum creatinine were collected. The diagnosis of AKI was based on the KDIGO criteria. The outcomes studied were development of AKI and hospital mortality. RESULTS: Urine abnormalities were seen in 71% of the patients. Proteinuria in 58.2%, haematuria in 17.3%, pyuria in 8.2% of patients and concurrent proteinuria and haematuria was seen in 13.6% of patients. AKI was seen in 28.2% of patients and hospital mortality was 24.5%. AKI was strongly associated with mortality. Proteinuria and haematuria were good predictors of development of AKI, more strongly when they occurred concurrently (p < 0.01). CONCLUSION: Our results suggest that urine analysis is a simple test, which can be used to predict development of AKI and mortality and may be used for risk stratification of Covid-19 patients, especially in low resource settings.


Assuntos
Lesão Renal Aguda/epidemiologia , Lesão Renal Aguda/urina , /urina , Lesão Renal Aguda/diagnóstico , Adulto , Idoso , Feminino , Hospitalização/tendências , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Proteinúria/diagnóstico , Proteinúria/epidemiologia , Proteinúria/urina , Estudos Retrospectivos , Urinálise/tendências
18.
Diabetes Res Clin Pract ; 172: 108620, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33316307

RESUMO

Familial partiallipodystrophy (FPLD)is a rare disorder associated withsevere insulin resistance, hypertriglyceridemia, lowserumHDLcholesterol and proteinuricrenaldisease. Although proteinuric renal disease is not common among in patients with partial lipodystrophy, we report a patient with Dunnigan type FPLD complicated by nephrotic syndrome which resolved following treatment with thePPARγagonist pioglitazone, CPAP, diet, and exercise.


Assuntos
Glomerulosclerose Segmentar e Focal/complicações , Hipoglicemiantes/uso terapêutico , Nefropatias/tratamento farmacológico , Lipodistrofia/fisiopatologia , Pioglitazona/uso terapêutico , Proteinúria/tratamento farmacológico , Adulto , Feminino , Humanos , Nefropatias/etiologia , Prognóstico , Proteinúria/etiologia
19.
Int J Clin Pract ; 75(4): e13946, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33332691

RESUMO

BACKGROUND: Hypoalbuminemia is frequently observed in patients with SARS-CoV-2 infection although its underlying mechanism and relationship with the clinical outcome still need to be clarified. METHODS: We retrospectively evaluated in patients with COVID-19 hospitalised at the Fatebenefratelli-Sacco Hospital in Milan, the prevalence of hypoalbuminemia, its association with the severity of COVID-19, with the levels of C-reactive protein, d-dimer and interleukin-6 and with clinical outcome over a follow-up period of 30 days. Urinalysis was evaluated in a subgroup of patients. RESULTS: Serum albumin levels <30 g/L were found in 105/207 (50.7%) patients at hospital admission. Overall, the median albumin value was 29.5 g/L (IQR 25-32.8). A negative association was found between albumin levels and severity of COVID-19 (P < .0001) and death (P = .003). An inverse correlation was observed between albumin and both C-reactive protein and D-dimer at hospital admission (r = -.487 and r = -.479, respectively; P < .0001). Finally, a positive correlation was found between albumin levels and eGFR (r = .137; P = .049). Proteinuria was observed in 75% of patients with available data and it did not differ between patients with hypoalbuminemia and those with albumin ≥30 g/L (81% and 67%, respectively; P = .09). CONCLUSION: In patients with COVID-19, hypoalbuminemia is common and observed in quite an early stage of pulmonary disease. It is strictly associated with inflammation markers and clinical outcome. The common finding of proteinuria, even in the absence of creatinine increase, indicates protein loss as a possible biomarker of local and systemic inflammation worthwhile to evaluate disease severity in COVID-19.


Assuntos
Pneumonia Viral , Proteinúria , Albumina Sérica , Idoso , /complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/complicações , Proteinúria/complicações , Estudos Retrospectivos
20.
Ter Arkh ; 92(6): 23-32, 2020 Jul 09.
Artigo em Russo | MEDLINE | ID: mdl-33346489

RESUMO

AIM: An evaluation of the effectiveness of immunosuppressive therapy (IST) and tonsillectomy (TE) in patients with IgA nephropathy (IgAN). MATERIALS AND METHODS: A retrospective cohort of the study included cases with biopsy proven primary IgAN (n=367, age 3412 years, men 55%). We used demographic and clinical and morphological parameters at the time of biopsy. Median followup period was 26 (10; 61) months. Outcomes were remission (complete or partial) and the progression of IgAN (defined as the start of dialysis or a decrease in glomerular filtration rate 50% from baseline). All patients received treatment with renin angiotensin system blockers. Evaluation of the effectiveness of therapy was carried out using propensity score (PS) methods matching, conventional double robust regression models with PS as independent covariate, and inverse probability weighting. Following patient subgroups were used for comparative analyses: with IST (n=176) and without IST (n=191); with TE (n=63) and without TE (n=304); without IST and without TE (IST-TE-; n=162); with TE and without IST (IST-TE+; n=29); with IST and without TE (IST+TE-; n=142); with IST and with TE (IST+ TE+; n=34). RESULTS: All PS methods used gave close estimates of the comparative effectiveness of treatment in different subgroups: 1) patients on monotherapy with corticosteroids (CS) and combination of CS with other immunosuppressants did not have significant differences in probabilities of IgAN progression (hazard ratio 0.919; 95% CI 0.3332.950) and remission (odds ratio 0.919; 95% CI 0.3792.344) and were further combined into a group of IST; 2) IST was significantly associated with the lower risk of disease progression and increased odds ratio for remission; 3) the positive effects of IST were limited to cases with proteinuria 2 g/24 h; 4) the likelihood of IgAN remission and progression did not differ significantly between TE+ and TE-, IST-TE+ and IST-TE- groups. There were no cases of disease progression in the IST+TE+ group. The cumulative renal survival was higher in the IST+TE+ group compared to IST+ TE- group (p=0.010), while the probability of remission did not differ. CONCLUSION: IST was associated with a lower risk of IgAN progression and increased probability of remission, while these effects of IST were limited to patients with proteinuria 2 g/24 h. TE in combination with IST is associated with an additional reduction in the risk of disease progression.


Assuntos
Glomerulonefrite por IGA , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/tratamento farmacológico , Humanos , Imunoglobulina A , Masculino , Proteinúria , Estudos Retrospectivos
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