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1.
Ecotoxicol Environ Saf ; 186: 109772, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31614297

RESUMO

Trichloroethylene (TCE) is a common organic solvent which can cause TCE hypersensitivity syndrome (THS) in exposure workers. THS is an adverse skin disorder with severe inflammatory kidney damage. Complement C3a receptor (C3aR) acts as a specific receptor for the key complement cleavage product C3a and involves multiple inflammatory responses, but the role of C3aR in TCE induced kidney inflammatory injury remains unknown. In this study, BALB/c mouse model of skin sensitization induced by TCE was set up in the presence or absence of C3aR antagonist (C3aRA). Kidney pathology and renal function, expression of inflammatory mediators and C3aR, changes in Th17 cell numbers, and activation of signal transducer and activator of transcription 3 (STAT3) in the kidney were examined. TCE sensitization produced histopathological and functional damage to the kidney, accompanied by increased levels of interleukin (IL-) 1ß, IL-6, and IL-23. Local accumulation of Th17 cells and enhanced phosphorylation of STAT3 were also seen in the impaired kidney in TCE sensitization-positive mice. C3aR was mainly located in the impaired glomerulus and upregulated in TCE sensitization-positive mice. C3aRA pretreatment alleviated the structural and functional kidney damage and the inflammatory cytokine and Th17 responses by TCE sensitization, and specifically reduced the phosphorylation of STAT3. Together, our results demonstrate that C3aR signaling promotes the inflammatory responses and regulates the accumulation of Th17 phenotype via phosphorylation of STAT3 in TCE sensitization induced inflammatory kidney damage. C3aR may serve as a potential therapeutic target in TCE sensitization mediated kidney injury.


Assuntos
Dermatite Alérgica de Contato/etiologia , Rim/efeitos dos fármacos , Receptores de Complemento/metabolismo , Células Th17/imunologia , Tricloroetileno/toxicidade , Animais , Citocinas/sangue , Dermatite Alérgica de Contato/imunologia , Dermatite Alérgica de Contato/patologia , Rim/imunologia , Rim/patologia , Testes de Função Renal , Camundongos , Camundongos Endogâmicos BALB C , Fenótipo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Células Th17/patologia
2.
Medicine (Baltimore) ; 98(41): e17388, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593089

RESUMO

It is not rare to find Immunoglobulin A (IgA) nephropathy (IgAN) combined with other glomerular diseases, which can be called compound IgAN (cIgAN). Till now, clinical-pathological investigation of cIgAN was lacking, especially the severity of "background IgAN lesions." This research aimed to investigate the incidence, clinical and pathological characteristics of cIgAN, and thus improve the understanding of the clinical significance of this combination.Patients with cIgAN diagnosed in Peking University People's Hospital from November 2012 to April 2018 were retrospectively analyzed. Patients with IgAN without compound glomerular diseases (sIgAN) were enrolled as a control group.Among 1407 patients diagnosed with IgAN, 80 (5.69%) were cIgAN patients. Compared with sIgAN, cIgAN patients had a significantly lower prevalence of microscopic hematuria and more urine protein. There were 10 pathological types of glomerular diseases combined with IgAN, led by diabetic nephropathy 37 (46.25%) and membranous nephropathy 14 (17.5%). Histologically, although the mesangial hypercellularity was comparable in 2 groups, cIgAN patients had a lower prevalence of endocapillary proliferation, segmental glomerulosclerosis, and cellular or fibrocellular crescents formation, as well as weaker immunofluorescence intensity for IgA and C3 (all P < .05). Eight out of 27 (29.63%) cIgAN patients with follow-up data (5-48 months) developed irreversible end-stage renal disease requiring dialysis.The order of incidence of concomitant diseases was similar to that of the pure diseases. The "background IgAN associated lesions" except mesangial hypercellularity were relatively mild in cIgAN group. Those might suggest that in some cases, IgAN seems to be a chance finding, and the combined diseases may play a more important role in the clinicopathological features of the patients than the nephritis caused by IgA deposition. While diagnosing IgAN, other combined glomerular diseases need to be carefully considered by nephrologists and pathologists.


Assuntos
Glomerulonefrite por IGA/patologia , Glomerulonefrite/patologia , Adulto , Biópsia , Feminino , Glomerulonefrite/epidemiologia , Glomerulonefrite/imunologia , Glomerulonefrite por IGA/complicações , Humanos , Incidência , Rim/imunologia , Rim/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
3.
Transplant Proc ; 51(7): 2274-2278, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31474292

RESUMO

BACKGROUND: Retransplantation is a treatment option in patients with end-stage renal failure due to graft loss. Outcomes of these patients due to high immunologic risk remain unclear. The aim of this study was to evaluate outcomes of renal retransplantation patients retrospectively. METHODS: Renal retransplant patients in our unit were evaluated retrospectively between 2010 and 2018. Patients' demographic characteristics, primary diseases, the causes of prior graft loss, immunologic status, desensitization protocols, the induction and maintenance treatments, the complications during the follow-up period, numbers of acute rejections, and the clinical prognosis were all detected from the patients' files. RESULTS: We retrospectively evaluated 17 patients who underwent a second or third renal allograft. Of these, 16 received a second and the remaining 1 patient received a third renal allograft. Immunologically, all of the 17 patients had negative flow cytometry crossmatch, 1 patient had a positive complement-dependent cytotoxicity crossmatch (Auto 12%), 16 patients had positive panel reactive antibody, the median HLA-mismatch was 3.5, and the score of donor-specific antibody relative intensity score (RIS) was 6.4 ± 6.3. Ten pretransplant patients had desensitization treatment. While scores for HLA-MM and HLA-RIS in the patients who had a desensitization therapy were determined higher, no statistical difference was observed (respectively, P = .28 and .55). No acute rejection episode developed. BK virus DNA viremia was detected in 4 patients during the posttransplant 6th month. We observed no patient death or no graft loss during the follow-up period. CONCLUSION: Although the retransplant patients who had a graft loss previously have high immunologic risks, retransplantation is reliable in these patients, but they should be followed up carefully in terms of BKV nephropathy.


Assuntos
Dessensibilização Imunológica/estatística & dados numéricos , Rejeição de Enxerto/cirurgia , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Reoperação/métodos , Adulto , Dessensibilização Imunológica/métodos , Feminino , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Teste de Histocompatibilidade/métodos , Humanos , Rim/imunologia , Falência Renal Crônica/etiologia , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
4.
Transplant Proc ; 51(6): 1796-1800, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399165

RESUMO

BACKGROUND: In kidney transplantation, donor recipient human leukocyte antigen (HLA)-DR mismatch signals high immunologic risk and portends inferior outcomes. We compared the impacts of depleting vs non-depleting antibody induction on the outcomes in kidney transplant recipients (KTRs) at different levels of HLA-DR mismatches. METHODS: Using the Organ Procurement and Transplantation Network/United Network for Organ Sharing database, we identified adult KTRs from 2001 to 2015 who received induction therapy with either depleting (thymoglobulin/alemtuzumab) or non-depleting (basiliximab/daclizumab) antibody and were discharged on calcineurin inhibitor/mycophenolic acid maintenance. Patients were then stratified by the number of donor-recipient HLA-DR mismatches (0, 1, 2) in both living donor (LD) and deceased donor (DD) KTRs. Under each HLA-DR mismatch category, long-term outcomes were compared for depleting vs non-depleting induction using a Cox model. RESULTS: A total of 63,821 LD (HLA-DR mismatches: 0, n = 6945 [depleting = 4409, non-depleting = 2536]; 1, n = 19,557 [depleting = 13,558, non-depleting = 6019]; and 2, n = 10,727 [depleting = 7694, non-depleting = 3033]) and 64,922 DD (HLA-DR mismatches: 0, n = 13,915 [depleting = 10,124, non-depleting = 3791]; 1, n = 27,994 [depleting = 20,454, non-depleting = 7540]; and 2, n = 23,013 [depleting = 16,908, non-depleting = 6105]) KTRs were included in the analysis. Adjusted patient death risk was significantly lower in the depleting vs non-depleting antibody induction group among DD kidney recipients (hazard ratio 0.90, 95% CI 0.85-0.96, P = .001) and trended lower among LD kidney recipients (HR 0.88, 95% 0.79-1.01, P = .05) with 2 HLA-DR mismatches. DISCUSSION: Our study found a patient survival benefit associated with the use of perioperative induction with depleting when compared to non-depleting antibody in KTRs with 2 HLA-DR mismatches and maintained on a calcineurin inhibitor/mycophenolic acid regimen.


Assuntos
Incompatibilidade de Grupos Sanguíneos/imunologia , Sobrevivência de Enxerto/imunologia , Antígenos HLA-DR/imunologia , Imunossupressão/métodos , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Adulto , Alemtuzumab/uso terapêutico , Anticorpos/imunologia , Soro Antilinfocitário/imunologia , Soro Antilinfocitário/uso terapêutico , Basiliximab/imunologia , Basiliximab/uso terapêutico , Inibidores de Calcineurina/imunologia , Inibidores de Calcineurina/uso terapêutico , Contraindicações de Procedimentos , Daclizumabe/imunologia , Daclizumabe/uso terapêutico , Bases de Dados Factuais , Feminino , Teste de Histocompatibilidade , Humanos , Rim/imunologia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/imunologia , Ácido Micofenólico/uso terapêutico , Modelos de Riscos Proporcionais , Resultado do Tratamento
5.
Fish Shellfish Immunol ; 93: 766-780, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31421241

RESUMO

Japanese flounder (Paralichthys olivaceus) is an important economic fish species farmed in China and other countries. It is susceptible to infection by Edwardsiella tarda, a severe fish pathogen with a broad host range. In this study, we employed high-throughput deep sequencing technology to identify, in a global scale, flounder kidney microRNAs (miRNAs) induced by E. tarda at different stages of infection. Differentially expressed miRNAs (DEmiRNAs) and mRNAs (DEmRNAs) exhibiting significantly altered expression levels before and after E. tarda infection were examined. A total of 96 DEmiRNAs were identified, for which 2779 target genes were predicted. Eighty-seven miRNA-mRNA pairs, involving 29 DEmiRNAs and 86 DEmRNAs, showed negative correlations in their expression patterns. GO and KEGG enrichment analysis revealed that the putative target genes of the DEmiRNAs were associated with diverse biological processes, cellular components, and molecular functions. One of the DEmiRNAs, pol-miR-182-5p, was demonstrated to regulate sphingosine-1-phosphate receptor 1 (PoS1PR1) negatively in a manner that depended on the specific interaction between the seed sequence of pol-miR-182-5p and the 3'-UTR of PoS1PR1. Overexpression of pol-miR-182-5p in flounder cells promoted apoptosis and inhibited cellular viability. Knockdown of PoS1PR1 in flounder enhanced E. tarda invasion and dissemination in fish tissues. These results provide new insights into miRNA-mediated anti-bacterial immunity in flounder.


Assuntos
Doenças dos Peixes/imunologia , Linguados/genética , Regulação da Expressão Gênica/imunologia , MicroRNAs/genética , Sequência de Aminoácidos , Animais , Edwardsiella tarda/fisiologia , Infecções por Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/veterinária , Linguados/imunologia , Perfilação da Expressão Gênica/veterinária , Rim/imunologia , Rim/metabolismo , MicroRNAs/imunologia , Alinhamento de Sequência , Fatores de Tempo
6.
Transplant Proc ; 51(8): 2660-2666, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31445765

RESUMO

BACKGROUND: Linear C4d staining in the peritubular capillaries is considered a sensitive and useful marker of active or chronic active antibody-mediated rejection (ABMR) in transplanted kidneys. However, the diagnostic significance of glomerular C4d deposits (gC4d) is still undetermined. The aim of this study is to evaluate the association of gC4d with clinicopathologic features and to assess its diagnostic value. METHODS: From 2013 to 2018, a total of 158 cases of allograft kidney biopsy specimens were obtained from the Korea University Anam Hospital. The histologic features were evaluated according to the Banff classification. The gC4d were determined through immunohistochemical analyses and classified based on scores of 0 to 3 according to the extent of gC4d. RESULTS: A total of 73 cases (46.2%) showed gC4d, and 37 cases (23.4%), 23 cases (14.6%), and 13 cases (8.2%) were classified with a score of 1+, 2+, and 3+, respectively. The gC4d showed a significant correlation with antibody-associated histologic lesions, including peritubular capillaritis, glomerulitis, and transplant glomerulopathy (P < .001). However, gC4d showed no significant association with cell-mediated injuries such as tubulitis, interstitial inflammation, acute tubular necrosis, and thrombotic microangiopathy. Although positive gC4d alone was associated with nonspecific findings without ABMR, most cases of gC4d combined with glomerulitis or transplant glomerulopathy showed typical histologic features of ABMR, clinically with higher antibody titers and severe functional deterioration. CONCLUSIONS: Glomerular C4d deposits may be an alternate useful marker in the diagnosis of active or chronic active ABMR when combined with histologic features of glomerular lesions.


Assuntos
Complemento C4b/análise , Glomerulonefrite/imunologia , Rejeição de Enxerto/diagnóstico , Transplante de Rim/efeitos adversos , Fragmentos de Peptídeos/análise , Complicações Pós-Operatórias/imunologia , Doença Aguda , Adulto , Anticorpos/imunologia , Biomarcadores/análise , Capilares/patologia , Doença Crônica , Complemento C4b/imunologia , Feminino , Glomerulonefrite/patologia , Rejeição de Enxerto/imunologia , Humanos , Rim/imunologia , Glomérulos Renais/imunologia , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/imunologia , Complicações Pós-Operatórias/patologia , República da Coreia , Microangiopatias Trombóticas/imunologia , Microangiopatias Trombóticas/patologia , Transplante Homólogo
7.
Transplant Proc ; 51(8): 2655-2659, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31345597

RESUMO

BACKGROUND: Rejection is still a barrier to long-term allograft survival, but there are not many reports of clinical outcomes according to rejection types. The purpose of this study was to investigate differences in pathologic features and graft outcomes of rejection on kidney transplant (KT). MATERIALS AND METHODS: We retrospectively analyzed 139 kidney transplant recipients diagnosed to rejection by allograft biopsy results between 2006 and 2018. We divided kidney transplant recipients into 3 groups as follows: T cell-mediated rejection (TCMR), antibody-mediated rejection, and mixed rejection. We investigated clinical characteristics, pathologic findings, death-censored graft survival rates, and patient survival rates among the 3 groups. RESULTS: Mean follow-up duration was 113.5 (SD, 80.6) months. The mixed rejection group was the youngest significantly. There were no significant differences of the proportion of sex, KT type, KT number, number of HLA mismatches, induction immunosuppressant, and maintenance immunosuppressant among the 3 groups. In pathologic findings, microvascular inflammation and C4d were significantly different among the 3 groups. Death-censored graft survival of mixed rejection was the least. In multivariate analysis, recipient age, TCMR, and positive C4d were the risk factors associated with graft failure. However, patient survival rates showed no significant differences among the 3 groups. CONCLUSIONS: Our study showed that mixed rejection had poor prognosis in comparison with TCMR and antibody-mediated rejection groups, and TCMR and positive C4d were the most important risk factors for graft survival. Therefore, constant monitoring through allograft biopsy and early treatment for rejection are very important in post-transplant clinical outcomes.


Assuntos
Aloenxertos/patologia , Rejeição de Enxerto/patologia , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Rim/patologia , Adulto , Aloenxertos/imunologia , Anticorpos/imunologia , Biópsia , Feminino , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto , Humanos , Rim/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Linfócitos T , Transplante Homólogo
8.
BMC Complement Altern Med ; 19(1): 186, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31349827

RESUMO

BACKGROUND: Oxidative stress and the inflammatory process are involved in ischemia-reperfusion (I/R) injury. Juglans mollis has been reported as having antioxidant activity, which could attenuate the damage caused by I/R. We evaluated whether a methanolic extract of Juglans mollis (JM) exhibits nephroprotective activity in a Wistar rat model of I/R injury. METHODS: Four groups of six rats were used: Sham, I/R, JM, and JM + I/R. Two groups were dosed with JM (300 mg/kg) for 7 days before I/R. I/R injury was induced by clamping the renal hilums for 45 min and then reperfusing the kidneys for 15 h. Blood samples were taken to evaluate the levels of alanine aminotransferase (ALT), blood urea nitrogen, creatinine, superoxide dismutase (SOD), malondialdehyde (MDA), interleukin 1ß (IL-1ß), IL-6, and tumor necrosis factor α (TNF-α). RESULTS: The levels of creatinine, ALT, MDA, IL-1ß, IL-6, and TNF-α were lower in JM + I/R than in I/R rats, whereas SOD level only was higher in JM + I/R than in Sham rats. No biochemical or histological damage was observed in JM rats compared with Sham rats; however, less histological damage was observed in JM + I/R rats compared with I/R rats. CONCLUSIONS: To our knowledge, this is the first report of nephroprotective activity of J. mollis against damage induced by I/R. This activity may be related to decreased levels of proinflammatory cytokines (IL-1ß, IL-6, and TNF-α) and modulation of oxidative stress markers (SOD and MDA) observed in the present study.


Assuntos
Anti-Inflamatórios/administração & dosagem , Juglans/química , Extratos Vegetais/administração & dosagem , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Creatinina/metabolismo , Humanos , Rim/efeitos dos fármacos , Rim/imunologia , Rim/metabolismo , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
9.
Transplant Proc ; 51(6): 1791-1795, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31301854

RESUMO

BACKGROUND: The 2013 Banff meeting updated the requirements for the diagnosis of acute/active antibody-mediated rejection (AAMR) in kidney allografts. There has been speculation that the changes lower the threshold for diagnosing AAMR, and may lead to possible unnecessary and expensive treatment. METHODS: We compared the 2013 Banff classification for AAMR to the previous 2007 Banff to determine if there was an increase in the number of patients receiving a diagnosis of AAMR and if the diagnosis affected allograft survival and post-biopsy 3-month and 6-month creatinine and eGFR values. RESULTS: A total of 212 renal allograft biopsies were compared to both 2007 and 2013 Banff classification requirements for AAMR. Ten patients (11 biopsies) met the 2007 criteria. An additional 15 patients (20 biopsies) met the 2013 criteria. These 2 groups showed no statistically significant demographic differences. By applying the 2013 Banff classification, we observed a 2.5-fold increase in the number of AAMR cases. One-year post-transplant allograft survival was higher in the 2013 group (.85 vs .55) and the 3-month and 6-month post-biopsy creatinine values were significantly lower for the 2013 group (1.6 ± .6 vs 3.3 ± 2.2, P value .01, and 1.7 ± .6 vs 3.4 ± 2.8, P value .03). The 3-month and 6-month eGFR values were higher in the 2013 group, although not statistically significant. CONCLUSIONS: These results suggest that use of Banff 2013 criteria in place of Banff 2007 may result in diagnosing milder and earlier cases of AAMR with the possibility of initiating earlier treatment and improving graft outcomes.


Assuntos
Anticorpos/análise , Rejeição de Enxerto/diagnóstico , Transplante de Rim/efeitos adversos , Escores de Disfunção Orgânica , Adulto , Aloenxertos/imunologia , Aloenxertos/patologia , Anticorpos/imunologia , Biópsia , Creatinina/análise , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto/imunologia , Humanos , Rim/imunologia , Rim/patologia , Masculino , Pessoa de Meia-Idade , Transplante Homólogo , Resultado do Tratamento
10.
Monoclon Antib Immunodiagn Immunother ; 38(4): 171-174, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31313968

RESUMO

Podoplanin (PDPN) is utilized as a specific marker of type I alveolar cells of lung and lymphatic endothelial cells of every tissue. Therefore, sensitive and specific monoclonal antibodies detecting PDPN are necessary for immunohistochemical analyses, especially using formalin-fixed paraffin-embedded tissues. Recently, we developed an anti-bear PDPN (bPDPN) mAb, PMab-247, which is useful for Western blot, flow cytometry, and immunohistochemical analyses. In this study, immunohistochemical analyses showed that PMab-247 strongly detected bPDPN, which is expressed in type I alveolar cells and lymphatic endothelial cells of bear lung and podocytes of bear kidney. These findings suggest that PMab-247 could be useful for pathophysiological analyses using immunohistochemistry.


Assuntos
Células Epiteliais Alveolares/metabolismo , Anticorpos Monoclonais/imunologia , Células Endoteliais/metabolismo , Rim/metabolismo , Pulmão/metabolismo , Glicoproteínas de Membrana/imunologia , Células Epiteliais Alveolares/imunologia , Animais , Células Endoteliais/imunologia , Imuno-Histoquímica/métodos , Rim/imunologia , Pulmão/imunologia , Ursidae
11.
Transplant Proc ; 51(7): 2302-2307, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31358448

RESUMO

PURPOSE: HLA antibodies have been shown to be associated with late graft loss. In this study, we defined the incidence and profiles of anti-HLA antibodies and their impact on graft outcome in long-term kidney recipients. METHODS: The sera of 118 kidney transplant recipients were screened for anti-HLA antibody presence. The antigen specificity of the detected HLA class I and class II antibodies was identified using a Luminex assay (Luminex Corp, Austin, TX, United States). Presence of donor specific antibodies (DSA) was examined in individuals with anti-HLA antibodies using the Luminex method. RESULTS: Anti-HLA class I and/or class II antibodies were detected in serum of 16.1% of the kidney transplant patients. The antibodies were directed against HLA class I antigens in 4 patients (21.1%), HLA class II antigens in 9 patients (47.4%), and both class I and class II antigens in 6 patients (31.6%). The overall prevalence of DSA was 10.2%. Anti-HLA antibodies were significantly associated with higher rate of cyclosporine use. Presence of DSA was associated with a lower rate of tacrolimus use, a higher rate of cyclosporine use, and lower donor age. Presence of anti-HLA antibodies was associated with higher acute cellular rejection and higher chronic active humoral rejection rates. Presence of DSA was associated with chronic active humoral rejection. CONCLUSION: The presence of either HLA antibodies or DSA significantly correlated with lower graft survival, poor transplant function, and proteinuria.


Assuntos
Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/imunologia , Antígenos HLA/imunologia , Isoanticorpos/sangue , Transplante de Rim/efeitos adversos , Adulto , Especificidade de Anticorpos , Feminino , Sobrevivência de Enxerto/imunologia , Humanos , Imunossupressores/uso terapêutico , Isoanticorpos/imunologia , Rim/imunologia , Transplante de Rim/métodos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Proteinúria/imunologia , Tacrolimo/uso terapêutico , Transplantes/imunologia , Resultado do Tratamento
12.
Transplant Proc ; 51(7): 2268-2273, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31358450

RESUMO

AIM: Sensitization to HLA antigens creates an immunologic barrier, linked to an increased risk of antibody-mediated rejection and poorer graft survival, that remains a persistent and often impenetrable deterrent to transplantation. Desensitization can improve transplantation rates in broadly sensitized kidney transplant recipients. We aimed to compare the clinical outcomes of immunologic high-risk kidney recipients who had desensitization treatment with the outcomes of those who did not. MATERIALS AND METHODS: We retrospectively evaluated patients who underwent desensitization protocol due to immunologic risk between 2010 and 2018. Living-donor transplantation patients with panel reactive antibody positivity, retransplantation, donor specific antibody, and/or single antigen bead positivity were included in the study. We excluded deceased-donor transplantation recipients. Demographic data (age, sex, etiology of end-stage renal disease, blood transfusions, pregnancy, etc), immunologic status (HLA-mismatch [HLA-MM], panel reactive antibody, donor specific antibody, etc), induction and maintenance of immunosuppressive medications, and complications (all-cause hospitalizations, episodes of acute rejections, etc) were noted. We compared data and clinical outcomes of patients who had desensitization (Group 1) with data and clinical outcomes of patients who had not had desensitization (Group 2). FINDINGS: There were 124 living-kidney donors (49 female, mean age 43.7 ± 12.2 years, mean body mass index [BMI] 25.8 ± 5.8 kg/m2, mean follow-up time 20.9 ± 14.6 months). Thirty-four of these patients (25 female, mean age 43.7 ± 12.5 years, mean follow-up time 26.1 ± 17.7 months, mean BMI 27 ± 6.5 kg/m2) had desensitization treatment (rituximab+plasmapheresis for 19 patients, rituximab for 11 patients, rituximab+plasmapheresis+intravenous immunoglobulin for 4 patients). Ninety patients (24 female, mean age 43.7 ± 12.2 years, mean follow-up time 18.9 ± 12.9 months, mean BMI 25.3 ± 5.4 kg/m2) had not had desensitization. There was no statistical difference between groups for age, sex, hepatitis serology, history of blood transfusion, history of pregnancy, or history of dialysis (P < .05 for all parameters). While scores for HLA-MM and HLA-relative intensity scale (RIS) were 2.7 ± 1.6 and 7.86 ± 6.2, respectively, in Group 1, in Group 2 the same scores were 2.1 ± 1.1 and 3.6 ± 2.5, respectively (P: .053 and .03). Delayed graft function, acute rejection episodes, and hospitalizations were similar between groups (P: .47, .29, and .34, respectively). Follow-up time and length of hospitalization were longer in Group 1 (P: .013 and .001, respectively). Total doses of ATG were higher in Group 1 patients (P: .007). CONCLUSION: Despite the higher HLA-MM and RIS scores, clinical outcomes in desensitized patients were found to be similar to those in nondesensitized patients for acute rejection episodes and hospitalizations. Desensitization with rituximab in patients with high HLA-RIS scores can prevent acute rejection and hospitalization.


Assuntos
Dessensibilização Imunológica/métodos , Rejeição de Enxerto/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Transplante de Rim/efeitos adversos , Rituximab/uso terapêutico , Adulto , Anticorpos/efeitos dos fármacos , Anticorpos/imunologia , Feminino , Seguimentos , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Antígenos HLA/imunologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Rim/imunologia , Falência Renal Crônica/etiologia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Plasmaferese , Período Pós-Operatório , Estudos Retrospectivos , Resultado do Tratamento
13.
Saudi J Kidney Dis Transpl ; 30(3): 719-722, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31249240

RESUMO

Recurrence of membranoproliferative glomerulonephritis (MPGN) is seen in 1965% cases of postrenal transplant resulting in graft loss in up to 35-50% of cases. A 31-year-old female, after 1% years on maintenance hemodialysis, underwent ABO compatible deceased donor kidney transplantation with basiliximab induction. During the immediate posttransplant period, the patient had delayed graft function, but achieved nadir creatinine of 0.9 mg/dL by 10 days. Nine months posttransplant, the patient developed fever, anasarca, and decrease in urine output with albuminuria 3+, active sediments in urine, serum creatinine 3.5 mg/dL, 24-h urine protein 7.5 g, and low C3. The patient underwent graft biopsy. Subsequently, the patient received pulse steroid for three days and five sessions of plasmapheresis. Renal biopsy report was suggestive of MPGN with focal crescents and acute tubular necrosis. Immunofluorescence showed Ig G3+, C3 3+, к 3+, and negative for λ or other immunoglobulins or complements. As her native kidney disease was immune-complex-mediated MPGN with no light chain restriction, paraffin tissue of the native kidney was reexamined for light chain restrictions by immunoperoxidase method, but did not show light chain restriction. The patient underwent extensive workup for paraproteinemias, but results were negative. Subsequently, she received four doses of bortezomib. The patient's serum creatinine got reduced to 0.8 mg/dL and proteinuria reduced to 800 mg/day. Our case is unique as we were not able to demonstrate monoclonal deposits in native kidney sample although there was recurrence of MPGN with monoclonal light chain deposits post transplant. Our findings emphasize the need for thorough evaluation of paraproteinemias in patients with idiopathic MPGN even in the absence of light chain deposition in biopsy.


Assuntos
Glomerulonefrite Membranoproliferativa/cirurgia , Transplante de Rim/efeitos adversos , Rim/cirurgia , Adulto , Feminino , Glomerulonefrite Membranoproliferativa/imunologia , Glomerulonefrite Membranoproliferativa/patologia , Humanos , Rim/imunologia , Rim/patologia , Recidiva , Fatores de Tempo , Resultado do Tratamento
14.
Saudi J Kidney Dis Transpl ; 30(3): 726-734, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31249242

RESUMO

Rapidly progressive renal failure in anti-neutrophil cytoplasmic antibody (ANCA)- associated renal disease customarily implies crescentic glomerulonephritis with approximately 50% of the glomeruli will have crescents. The tubulointerstitial inflammation is often proportionate to the glomerular inflammation and may have granulomatous pattern adjacent to the glomeruli or an inflamed vessel. A 77-year-old male with rapidly progressive renal failure was myeloperoxidase-ANCA positive, and renal histopathology revealed thrombotic microangio-pathy, significant interstitial inflammation, interstitial granulomas, and arteritis. Pathology is unique for the paucity of the classical crescents and the myriad of extraglomerular features. His renal function improved and stabilized after induction with cyclophosphamide and maintenance with azathioprine.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Anticorpos Anticitoplasma de Neutrófilos/análise , Glomerulonefrite/patologia , Rim/patologia , Peroxidase/imunologia , Insuficiência Renal/patologia , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Azatioprina/uso terapêutico , Ciclofosfamida/uso terapêutico , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/imunologia , Humanos , Imunossupressores/uso terapêutico , Rim/efeitos dos fármacos , Rim/imunologia , Masculino , Insuficiência Renal/tratamento farmacológico , Insuficiência Renal/imunologia , Resultado do Tratamento
15.
Nat Immunol ; 20(7): 902-914, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31209404

RESUMO

Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, T cells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses. We found evidence of local activation of B cells correlated with an age-associated B-cell signature and evidence of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, implying a potentially central role in cell trafficking. Gene expression of immune cells in urine and kidney was highly correlated, which would suggest that urine might serve as a surrogate for kidney biopsies.


Assuntos
Rim/imunologia , Nefrite Lúpica/imunologia , Biomarcadores , Biópsia , Análise por Conglomerados , Biologia Computacional/métodos , Células Epiteliais/metabolismo , Citometria de Fluxo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Imunofenotipagem , Interferons/metabolismo , Rim/metabolismo , Rim/patologia , Leucócitos/imunologia , Leucócitos/metabolismo , Nefrite Lúpica/genética , Nefrite Lúpica/metabolismo , Nefrite Lúpica/patologia , Linfócitos/imunologia , Linfócitos/metabolismo , Anotação de Sequência Molecular , Células Mieloides/imunologia , Células Mieloides/metabolismo , Análise de Célula Única , Transcriptoma
16.
BMC Complement Altern Med ; 19(1): 149, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31238921

RESUMO

BACKGROUND: The kidney is an essential organ required by the body to perform several important functions. Nephrotoxicity is one of the most prevailing kidney complications that result from exposure to an extrinsic or intrinsic toxicant, which increase the need for the acquisition of proper remedies. Recently, natural remedies are gaining great attention owed to the fact that they have fewer side effects than most conventional drugs. METHODS: The current study recorded a new therapeutic role of the well-known medicinal plants for kidney stones [Ammi visnaga (AVE), Petroselinum crispum (PCE), Hordeum vulgare (HVE), and Cymbopogon schoenanthus (CSE)]. Hence, the aqueous extracts of these plants examined against CCl4-induced toxicity in mammalian kidney (Vero) cells. RESULTS: These extracts showed the presence of varying amounts of phenolic and triterpenoid compounds, as well as vitamin C. Owing to the antioxidant potential of these constituents, the extracts suppressed the CCl4-induced oxidative stress significantly (p < 0.05) by scavenging the reactive oxygen species and enhancing the cellular antioxidant indices. In addition, these extracts significantly (p < 0.05) reduced the CCl4-induced inflammation by inhibiting the gene expression of NF-кB, iNOS, and in turn the level of nitric oxide. Consequently, the morphological appearance of Vero cells, cellular necrosis, and the gene expression of kidney injury molecule-1 (a marker of renal injury) after these treatments were improved. The AVE improved CCl4-induced oxidative and inflammatory stress in Vero cells and showed a more potent effect than the commonly used alpha-Ketoanalogue drug (ketosteril) in most of the studied assays. CONCLUSION: Thus, the studied plant extracts, especially AVE can be considered as promising extracts in the management of nephrotoxicity and other chronic diseases associated with oxidative stress and inflammation.


Assuntos
Ammi/química , Cymbopogon/química , Hordeum/química , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Petroselinum/química , Extratos Vegetais/farmacologia , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Rim/imunologia , NF-kappa B/genética , NF-kappa B/imunologia , Óxido Nítrico/imunologia , Fenóis/química , Fenóis/isolamento & purificação , Fenóis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Sementes/química , Células Vero
17.
Microb Pathog ; 133: 103559, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31132417

RESUMO

Aeromonas salmonicida, the oldest known fish pathogen and currently endemic throughout most of the world in both fresh and marine waters, causes severe economic losses to the salmon farming industry. Although there have been many studies on the prevention of furunculosis over the past few decades, it is still prevalent in many fisheries. In this study, a recombinant adenovirus vaccine candidate harboring the highly immunogenic Vapa gene (pAd-easy-cmv-Vapa) was successfully constructed and tested. The immune protection rate and specific antibody levels in the peripheral blood were then determined after immunizing rainbow trout. In addition, relative levels of IgM and IgT in the head kidney and hindgut before and after immunization were measured by quantitative reverse transcription PCR. Western blotting results indicated that the recombinant adenovirus could infect HEK-293 cells and express the A layer protein (encoded by Vapa). Further, survival analysis of fish 28 days after challenge showed that immunization significantly lowered the mortality rate (40%) compared to that in the control group (76.6%) and empty vector group (73.6%). This also led to an increase in specific antibodies in peripheral serum. In addition, levels of IgM and IgT in the head kidney and hindgut were increased to varying degrees. In conclusion, our research provides a candidate vaccine for the prevention of Aeromonas salmonicida A450 infection in rainbow trout and lays the foundation for future research on adaptive immune mechanisms associated with rainbow trout antibodies.


Assuntos
Adenoviridae/genética , Aeromonas salmonicida/imunologia , Doenças dos Peixes/prevenção & controle , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Imunização , Vacinas Sintéticas/imunologia , Imunidade Adaptativa , Vacinas contra Adenovirus , Aeromonas salmonicida/genética , Sequência de Aminoácidos , Animais , Anticorpos , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Vacinas Bacterianas/genética , Vacinas Bacterianas/imunologia , Doenças dos Peixes/imunologia , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Células HEK293 , Interações Hospedeiro-Patógeno , Humanos , Imunoglobulina M , Rim/imunologia , Oncorhynchus mykiss , Vacinação , Vacinas Sintéticas/genética
18.
Inflamm Res ; 68(6): 511-523, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31037316

RESUMO

OBJECTIVE: Chicoric acid (CA) is a natural product with promising antioxidant and anti-inflammatory properties; however, its protective effect on methotrexate (MTX)-induced acute kidney injury (AKI) hasn't been reported. We investigated the effect of CA on MTX-induced AKI in rats, pointing to the role of NF-κB/NLRP3 inflammasome and Nrf2/ARE/HO-1 signaling. MATERIALS AND METHODS: Wistar rats received 25 mg/kg and 50 mg/kg CA for 15 days and a single injection of MTX at day 16. At day 19, the rats were killed, and samples were collected for analyses. RESULTS: MTX induced a significant increase in serum creatinine and urea, and kidney Kim-1, reactive oxygen species (ROS), malondialdehyde and nitric oxide levels. In addition, MTX-induced rats exhibited multiple histopathological alterations, diminished antioxidant defenses, and decreased expression of Nrf2, NQO-1 and HO-1. CA prevented histological alterations, ameliorated kidney function markers, attenuated ROS production and lipid peroxidation, and boosted antioxidant defenses. CA suppressed the expression of NF-κB p65, NLRP3, caspase-1 and IL-1ß in the kidney of MTX-induced rats. Furthermore, CA inhibited MTX-induced apoptosis as evidenced by the decreased expression of BAX and caspase-3, and increased Bcl-2 gene expression. CONCLUSIONS: CA prevented MTX-induced AKI through activation of Nrf2/ARE/HO-1 signaling, and attenuation of ROS-induced activation of NF-κB/NLRP3 inflammasome signaling.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Lesão Renal Aguda/imunologia , Ácidos Cafeicos/farmacologia , Ácidos Cafeicos/uso terapêutico , Succinatos/farmacologia , Succinatos/uso terapêutico , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/patologia , Animais , Elementos de Resposta Antioxidante/imunologia , Apoptose/efeitos dos fármacos , Antagonistas do Ácido Fólico , Heme Oxigenase (Desciclizante)/imunologia , Rim/efeitos dos fármacos , Rim/imunologia , Rim/patologia , Masculino , Metotrexato , Fator 2 Relacionado a NF-E2/imunologia , NF-kappa B/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Ratos Wistar , Transdução de Sinais , Regulação para Cima/efeitos dos fármacos
19.
Biomed Pharmacother ; 115: 108904, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31060008

RESUMO

Membranous nephropathy (MN) is one of the leading causes of nephrotic syndrome in adults. However, the current treatment of MN has been a matter of fierce debate for decades, and the needs for more advanced pharmaceuticals are critical for improving the treatment strategies. Sanqi oral solution (SQ), mainly consisting of Radix Astragali and Radix Notoginseng, is a formulated product to treat chronic kidney disease for over 20 years with good efficiency in clinic, while the role of SQ on MN remains unclear. In this study, by establishing an experimental rat model of membranous nephropathy induced by cationic Bovine Serum Albumin (C-BSA), we tried to investigate the effects of SQ. We found that administration of SQ ameliorated MN by reducing proteinuria, elevating serum albumin, and ameliorating pathological renal damages. SQ also significantly reduced the C3 and IgG depositions, and restored podocin and synaptopodin expressions. Furthermore, SQ inhibited the activation of nuclear factor-kappa B (NF-κB) signaling pathway. Our results provide evidence that SQ exerts a novel therapeutic effect on MN via reducing proteinuria, ameliorating renal damage and restoring podocyte injuries, which are associated with the suppression of NFκB.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Rim/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Podócitos/efeitos dos fármacos , Administração Oral , Animais , Biomarcadores/sangue , Biomarcadores/urina , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Glomerulonefrite Membranosa/imunologia , Glomerulonefrite Membranosa/patologia , Rim/imunologia , Rim/ultraestrutura , Masculino , Podócitos/imunologia , Podócitos/ultraestrutura , Ratos Sprague-Dawley , Soluções
20.
J Agric Food Chem ; 67(22): 6202-6211, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31091873

RESUMO

Allopurinol is the first-line medication for hyperuricemia treatment. However, severe drug-related adverse effects have often been reported among patients who received allopurinol administration. This study is aimed at evaluating the possible attenuation effects of highly acylated anthocyanins from purple sweet potato (HAA-PSP) on hyperuricemia and kidney inflammation in hyperuricemic mice treated with allopurinol. In comparison with 5 mg kg-1 allopurinol used alone, the combination of 25 mg kg-1 HAA-PSP and 2.5 mg kg-1 allopurinol could not only reduce serum uric acid level in hyperuricemic mice but also attenuate the kidney damage, as indicated by the level of serum biomarkers as well as histopathological examination. The inflammatory response was partially mitigated by inhibiting the protein expression of typical cytokines in the kidney. Our findings provide new evidence for the supplementary therapeutic potential of HAA-PSP with allopurinol on hyperuricemia and inflammation-related syndromes. Moreover, this study provides a theoretical basis for assessing the potential of anthocyanin-rich foods in health.


Assuntos
Antocianinas/administração & dosagem , Antocianinas/química , Hiperuricemia/tratamento farmacológico , Ipomoea batatas/química , Rim/imunologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Acilação , Alopurinol/administração & dosagem , Alopurinol/química , Animais , Modelos Animais de Doenças , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/química , Humanos , Hiperuricemia/sangue , Hiperuricemia/imunologia , Rim/efeitos dos fármacos , Masculino , Camundongos , Ácido Úrico/sangue
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