RESUMO
PURPOSE: BK Polyomavirus (BKPyV) infection manifests as renal inflammation and can cause kidney damage. Tumor necrosis factor-α (TNF-α) is increased in renal inflammation and injury. The aim of this study was to investigate the effect of TNF-α blockade on BKPyV infection. METHODS: Urine specimens from 22 patients with BKPyV-associated nephropathy (BKPyVN) and 35 non-BKPyVN kidney transplant recipients were analyzed. RESULTS: We demonstrated increased urinary levels of TNF-α and its receptors, TNFR1 and TNFR2, in BKPyVN patients. Treating BKPyV-infected human proximal tubular cells (HRPTECs) with TNF-α stimulated the expression of large T antigen and viral capsid protein-1 mRNA and proteins and BKPyV promoter activity. Knockdown of TNFR1 or TNFR2 expression caused a reduction in TNF-α-stimulated viral replication. NF-κB activation induced by overexpression of constitutively active IKK2 significantly increased viral replication and the activity of the BKPyV promoter containing an NF-κB binding site. The addition of a NF-κB inhibitor on BKPyV-infected cells suppressed viral replication. Blockade of TNF-α functionality by etanercept reduced BKPyV-stimulated expression of TNF-α, interleukin-1ß (IL-1ß), IL-6 and IL-8 and suppressed TNF-α-stimulated viral replication. In cultured HRPTECs and THP-1 cells, BKPyV infection led to increased expression of TNF-α, interleukin-1 ß (IL-1ß), IL-6 and TNFR1 and TNFR2 but the stimulated magnitude was far less than that induced by poly(I:C). This may suggest that BKPyV-mediated autocrine effect is not a major source of TNFα. CONCLUSION: TNF-α stimulates BKPyV replication and inhibition of its signal cascade or functionality attenuates its stimulatory effect. Our study provides a therapeutic anti-BKPyV target.
Assuntos
Vírus BK , Infecções por Polyomavirus , Humanos , Vírus BK/genética , Fator de Necrose Tumoral alfa , Receptores Tipo I de Fatores de Necrose Tumoral , Receptores Tipo II do Fator de Necrose Tumoral/genética , NF-kappa B , Interleucina-6 , Infecções por Polyomavirus/metabolismo , Infecções por Polyomavirus/patologia , InflamaçãoRESUMO
Solid organ transplant recipients have an increased risk of tuberculosis (TB). Due to the use of immunosuppressants, the incidence of TB among solid organ transplant recipients has been consistently reported to be higher than that among the general population. TB frequently develops within the first year after transplantation when a high level of immunosuppression is maintained. Extrapulmonary TB and disseminated TB account for a substantial proportion of TB among solid organ transplant recipients. Treatment of TB among recipients is complicated by the drug-drug interactions between anti-TB drugs and immunosuppressants. TB is associated with an increased risk of graft rejection, graft failure and mortality. Detection and management of latent TB infection among solid organ transplant candidates and recipients have been recommended. However, strategy to mitigate the risk of TB among solid organ transplant recipients has not yet been established in Taiwan. To address the challenges of TB among solid organ transplant recipients, a working group of the Transplantation Society of Taiwan was established. The working group searched literatures on TB among solid organ transplant recipients as well as guidelines and recommendations, and proposed interventions to strengthen TB prevention and care among solid organ transplant recipients.
Assuntos
Transplante de Órgãos , Tuberculose , Humanos , Taiwan/epidemiologia , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Transplante de Órgãos/efeitos adversos , Antituberculosos/uso terapêutico , Imunossupressores/efeitos adversosRESUMO
BACKGROUND: Patients with end-stage renal disease (ESRD) under hemodialysis (HD) are at greater risks of infectious spondylitis (IS), but there is no reliable predictor that facilitate early detection of this relatively rare and insidious disease. METHODS: A retrospective review of the medical records from patients with ESRD under HD over a 12-year period was performed at a tertiary teaching hospital, and those with a first-time diagnosis of IS were identified. A 1:4 propensity score-matched case-control study was carried out, and baseline characteristics, underlying diseases, and laboratory data were compared between the study group and the control group, one month before the date of diagnosis or the index date respectively. RESULTS: A total of 16 patients with IS were compared with 64 controls. After adjustment, recent access operation (odds ratio [OR], 13.27; 95% confidence interval [CI], 3.53 to 49.91; p < 0.001), degenerative spinal disease (OR, 12.87; 95% CI, 1.89 to 87.41; p = 0.009), HD through a tunneled cuffed catheter (OR, 6.75; 95% CI, 1.74 to 26.14; p = 0.006), low serum levels of hemoglobin, albumin, as well as high levels of red blood cell volume distribution width (RDW), alkaline phosphatase (ALP), and high sensitivity C-reactive protein were significant predictors for a IS diagnosis one month later. Receiver operating characteristic curves for hemoglobin, RDW, ALP, and albumin all showed good discrimination. The further multivariate models identified both high serum ALP levels and low serum RDW levels following a recent access intervention in patients with relatively short HD vintages may be indicative of the development of IS. CONCLUSION: Patients under HD with relatively short HD vintages showing either elevated ALP levels or low RDW levels following a recent access intervention should prompt clinical awareness about IS for timely diagnosis.
Assuntos
Infecções Bacterianas/diagnóstico , Falência Renal Crônica/terapia , Doenças Raras/diagnóstico , Diálise Renal/efeitos adversos , Espondilite/diagnóstico , Adulto , Fosfatase Alcalina/sangue , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos de Casos e Controles , Volume de Eritrócitos , Feminino , Hemoglobina A/análise , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Curva ROC , Doenças Raras/etiologia , Diálise Renal/instrumentação , Estudos Retrospectivos , Sensibilidade e Especificidade , Espondilite/etiologiaRESUMO
BACKGROUND/PURPOSE: A reliable noninvasive prognostic factor of ANCA-associated vasculitis (AAV) is still lacking, but little research has focused on the value of MPO-ANCA titers in patients with active vasculitis. This study explored the prognostic significance of MPO-ANCA titer in active AAV patients. METHODS: Ninety-seven inpatients diagnosed with MPO-ANCA associated vasculitis at Linkou Chang Gung Memorial hospital and Keelung Chang Gung Memorial hospital from January 2005 to December 2016 were enrolled. Serum ANCA titers and basic characteristics of these patients at diagnosis were collected completely Medical records since AAV diagnosis were reviewed to evaluate two years renal and patient outcome. RESULTS: The patients were divided into the two groups according to the median ANCA titers, the more than four times of the normal cut-off value group (high titer group) and the less ANCA titer group (low titer group). The high titer group had significant poor initial renal function (eGFR 16.7 vs 40.7 mL/min/1.73 m2, P = 0.006), and significantly lower two-year renal survival (Log rank P < 0.001). Whereas patient survival (Log rank P = 0.894) was not different The Cox regression models revealed that baseline Birmingham Vasculitis Activity Score, eGFR and a 4-fold increase in ANCA titer were associated with the requirement of permanent dialysis. In the subgroup analysis, the ANCA titer was still an important risk factor for renal outcomes (P = 0.036) in patients with better initial renal function (eGFRâ§15 mL/min). CONCLUSION: This study demonstrated that higher MPO-ANCA titers at diagnosis was associated with poor initial renal function and 2-year renal outcomes.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Anticorpos Anticitoplasma de Neutrófilos/sangue , Falência Renal Crônica/etiologia , Falência Renal Crônica/terapia , Adulto , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/enzimologia , Biomarcadores/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Peroxidase/imunologia , Prognóstico , Modelos de Riscos Proporcionais , Diálise Renal , Estudos Retrospectivos , Índice de Gravidade de Doença , Taxa de SobrevidaRESUMO
BACKGROUND: Aggregation of end-stage renal disease (ESRD) has been observed in families of European origin, as well as those of African origin. However, it is not well documented if this disease aggregates in Asian families. Furthermore, the contribution of genetic factors and shared environmental factors to family aggregation remains unclear. STUDY DESIGN: Population-based cross-sectional cohort study. SETTING & PARTICIPANTS: All 23,422,955 individuals registered in the Taiwan National Health Insurance Research Database in 2013. Among these, 47.45%, 57.45%, 47.29%, and 1.51% had a known parent, child, sibling, or twin, respectively. We identified 87,849 patients who had a diagnosis of ESRD. PREDICTOR: Family history of ESRD. OUTCOMES & MEASUREMENTS: ESRD and heritability defined as the proportion of phenotypic variance attributable to genetic factors. RESULTS: Having an affected first-degree relative with ESRD was associated with an adjusted relative risk of 2.46 (95% CI, 2.32-2.62). Relative risks were 96.38 (95% CI, 48.3-192.34) for twins of patients with ESRD, 2.15 (95% CI, 2.02-2.29) for parents, 2.78 (95% CI, 2.53-3.05) for offspring, 4.96 (95% CI, 4.19-5.88) for siblings, and 1.66 (95% CI, 1.54-1.78) for spouses without genetic similarities. Heritability in this study was 31.1% to 11.4% for shared environmental factors and 57.5% for nonshared environmental factors. LIMITATIONS: This was a registry database study and we did not have detailed information about clinical findings or the definite causes of ESRD. CONCLUSIONS: This whole population-based family study in Asia confirmed, in a Taiwanese population, that a family history of ESRD is a strong risk factor for this disease. Moderate heritability was noted and environmental factors were related to disease. Family history of ESRD is an important piece of clinical information.
Assuntos
Povo Asiático/genética , Família , Falência Renal Crônica/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/estatística & dados numéricos , Criança , Pré-Escolar , Estudos Transversais , Bases de Dados Factuais , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Falência Renal Crônica/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Risco , Taiwan/epidemiologia , Adulto JovemRESUMO
BACKGROUND/PURPOSE: Polyomavirus BK (BKV) reactivation causes allograft dysfunction in some kidney transplant recipients. The use of mammalian target of rapamycin (mTOR) inhibitor-based immunotherapy is associated with a lower incidence of polyomavirus-associated nephropathy compared with other immunosuppressants. This retrospective study assessed whether conversion to mTOR inhibitor-based immunotherapy directly reduced urinary BKV load. METHODS: A total of 63 kidney recipients were divided into mTOR inhibitor-conversion (21 patients) and nonconversion (42 patients) groups. Urinary BKV loads were determined before and at least 6 months after the conversion. RESULTS: The results demonstrated that urinary BKV titer was significantly reduced in the conversion group (3.94 ± 0.43 copies (log)/mL to 2.49 ± 0.19 copies (log)/mL) and remained unaltered in the nonconversion group (3.19 ± 0.20 copies (log)/mL to 2.90 ± 0.20 copies (log)/mL). In addition, the percentage of patients with reduced urinary BKV load was significantly higher in the conversion group (76.2% vs. 42.9%). The estimated glomerular filtration rate after 24 months mTOR inhibitor conversion was significantly increased compared with that in the nonconversion group. Conversion to mTOR-inhibitor-based immunotherapy was the only factor associated with an increase in estimated glomerular filtration rate. CONCLUSION: This study reveals an association of conversion to mTOR-inhibitor-based immunotherapy with the reduction of urinary BKV load.
Assuntos
Vírus BK/efeitos dos fármacos , Imunoterapia , Nefropatias/epidemiologia , Transplante de Rim , Infecções por Polyomavirus/tratamento farmacológico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Adulto , Creatinina/sangue , Everolimo/uso terapêutico , Feminino , Taxa de Filtração Glomerular , Humanos , Imunossupressores/uso terapêutico , Nefropatias/virologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/virologia , Estudos Retrospectivos , Sirolimo/uso terapêutico , Taiwan , Carga Viral/efeitos dos fármacosRESUMO
Polyomavirus BK (BKV) infection is an important cause of renal allograft failure. Viral microRNAs are known to play a crucial role in viral replication. This study investigated the expression of BKV-encoded microRNAs (miR-B1) in patients with polyomavirus-associated nephropathy (PVAN) and their role in viral replication. Following BKV infection in renal proximal tubular cells, the 3p and 5p miR-B1 levels were significantly increased. Cells transfected with the vector containing the miR-B1 precursor (the miR-B1 vector) showed a significant increase in expression of 3p and 5p miR-B1 and decrease in luciferase activity of a reporter containing the 3p and 5p miR-B1 binding sites, compared to cells transfected with the miR-B1-mutated vector. Transfection of the miR-B1 expression vector or the 3p and 5p miR-B1 oligonucleotides inhibited expression of TAg. TAg-enhanced promoter activity and BKV replication were inhibited by miR-B1. In contrast, inhibition of miR-B1 expression by addition of miR-B1 antagomirs or silencing of Dicer upregulated the expression of TAg and VP1 proteins in BKV-infected cells. Importantly, patients with PVAN had significantly higher levels of 3p and 5p miR-B1 compared to renal transplant patients without PVAN. In conclusion, we demonstrated that (1) miR-B1 expression was upregulated during BKV infection and (2) miR-B1 suppressed TAg-mediated autoregulation of BKV replication. Use of miR-B1 can be evaluated as a potential treatment strategy against BKV infection.
Assuntos
Vírus BK/fisiologia , Rejeição de Enxerto/virologia , Transplante de Rim , MicroRNAs/fisiologia , Infecções por Polyomavirus/virologia , RNA Viral/fisiologia , Replicação Viral , Antígenos Virais de Tumores/genética , Vírus BK/genética , Proteínas do Capsídeo/genética , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Regulação para Baixo , Regulação Viral da Expressão Gênica , Inativação Gênica , Homeostase , Humanos , MicroRNAs/genética , Biossíntese de Proteínas , RNA Viral/genética , Ribonuclease III/genética , Ribonuclease III/metabolismo , Transcrição GênicaRESUMO
BACKGROUND: Numerous successful pregnancy outcomes have been reported after kidney transplantation, but until now, there have been no reports of healthy twin deliveries through in vitro fertilization treatment in high-gestation aged women with a long post-transplant duration. In our report, we present a case of a high-gestation aged kidney transplant recipient who successfully delivered healthy twins with the aid of in vitro fertilization. CASE PRESENTATION: At the age of 29, a woman with end-stage kidney disease caused by immunoglobin A nephropathy underwent kidney transplantation. She had a history of premature ovarian failure and had been on continuous ambulatory peritoneal dialysis since the age of 18. Eleven years after starting dialysis, she received a cadaveric kidney transplant. Despite being infertile for 7 years after transplantation, she wished to have children. In vitro fertilization embryo transfer was conducted after failure of ovarian stimulation, considering her age and premature ovarian failure. The patient successfully delivered twins at 29 weeks gestation via cesarean section, as the first fetus presented in breech position. The first newborn weighed 945 g and the second weighed 855 g, with no other congenital abnormalities found. One year after childbirth, neither the recipient nor her babies experienced any fatal complications. CONCLUSIONS: A woman who underwent kidney transplantation and has stage 3 CKD may successfully deliver healthy twins through in vitro fertilization embryo transfer, even if she is of advanced maternal age and has a long post-transplant period. However, there is a risk of preterm premature rupture of membrane in such cases.
Assuntos
Fertilização in vitro , Transplante de Rim , Humanos , Feminino , Gravidez , Adulto , Gravidez de Gêmeos , Resultado da Gravidez , Falência Renal Crônica/cirurgia , Transferência EmbrionáriaRESUMO
Recent studies have suggested that BK polyomavirus (BKPyV) may be associated with the development of urothelial carcinoma. In Merkel cell carcinoma, TAg and tAg are the major viral proteins of Merkel cell polyomavirus with oncogenic potential. In this study, we aimed to distinguish the role of TAg and tAg in cell migration. Our result demonstrated that ERK was phosphorylated in human renal tubular cells expressing its TAg and tAg after BKPyV infection. Treatment with the ERK inhibitor U0126 suppressed BKPyV gene expression and reduced BKPyV replication. Both TAg and tAg induced cell migration via ERK-dependent signaling. Furthermore, the expression of TAg and tAg had a significant regulatory effect on focal adhesion molecules in renal proximal tubular cells, which strongly suggests that alterations in the focal adhesion complexes are critically involved in TAg and tAg-induced cell migration. Gelatin zymography profiling revealed that TAg regulates the expression and activity of MMP-2 and MMP-9, but not tAg. Interestingly, TAg regulates the expression and activity of MMP-9 through ERK signaling, whereas MMP-2 is regulated through an ERK-independent pathway. Unbalanced ERK pathway activity is frequently observed in many cancers, while MMP proteins are usually overexpressed in aggressive tumors. These findings support the view that BKPyV is an oncogenic virus.
RESUMO
INTRODUCTION: BK Polyomavirus (BKPyV) infection is a common complication in kidney transplant recipients and can result in poor outcome and graft failure. Currently, there is no known effective antiviral agent. This study investigated the possible antiviral effects of Interferon alpha (IFNα) and its induced protein, MxA, against BKPyV. METHODS: In vitro cell culture experiments were conducted using human primary renal proximal tubular epithelial cells (HRPTECs). We also did animal studies using Balb/c mice with unilateral kidney ischemic reperfusion injury. RESULTS: Our results demonstrated that IFNα effectively inhibited BKPyV in vitro and murine polyomavirus in animal models. Additionally, IFNα and MxA were found to suppress BKPyV TAg and VP1 production. Silencing MxA attenuated the antiviral efficacy of IFNα.We observed that MxA interacted with BKPyV TAg, causing it to remain in the cytosol and preventing its nuclear translocation. To determine MxA's essential domain for its antiviral activities, different mutant MxA constructs were generated. The MxA mutant K83A retained its interaction with BKPyV TAg, and its antiviral effects were intact. The MxA T103A mutant, on the other hand, abolished GTPase activity and lost its protein-protein interaction with BKPyV TAg, and lost its antiviral effect. CONCLUSION: IFNα and its downstream protein, MxA, have potent antiviral properties against BKPyV. Furthermore, our findings indicate that the interaction between MxA and BKVPyV TAg plays a crucial role in determining the anti-BKPyV effects of MxA.
RESUMO
Background: Statins are frequently prescribed with direct oral anticoagulants (DOACs), and previous studies have raised concerns about the increased risk of intracerebral hemorrhage or other major bleeding in concurrent statins and DOACs use. The objective of this study is to evaluate the risk of major bleeding in non-valvular atrial fibrillation patients taking DOACs with or without statins. Methods: This nationwide, retrospective cohort study used data from the Taiwan National Health Insurance Research Database, enrolled a total of 90,731 non-valvular atrial fibrillation patients receiving rivaroxaban, dabigatran, apixaban or edoxaban from January 1st, 2012 to December 31st, 2017. Major bleeding was defined as a hospitalization or emergency department visit with a primary diagnosis of intracerebral hemorrhage, gastrointestinal tract bleeding, urogenital tract bleeding, or other sites of bleeding. Adjusted incidence rate ratios (IRR) and differences of major bleeding between person-quarters of DOACs with or without statins were estimated using a Poisson regression and inverse probability of treatment weighting using the propensity score. Results: 50,854 (56.0%) of them were male with a mean age of 74.9 (SD, 10.4) years. Using DOACs without statins as a reference, the adjusted IRR for all major bleedings in concurrent use of DOACs and statins was 0.8 (95% CI 0.72-0.81). Lower major bleeding risk was seen in both low-to-moderate-intensity statins (IRR: 0.8, 95% CI 0.74-0.84) and high-intensity statins (IRR: 0.8, 95% CI 0.74-0.88). Concurrent use of DOACs and statins decreased the risk for intracerebral hemorrhage with an IRR of 0.8 (95% CI 0.66-0.93), and gastrointestinal tract bleeding with an IRR of 0.7 (95% CI 0.69-0.79). The protective effect of statins on intracerebral hemorrhage was observed only in female patients (IRR 0.67, 95% CI 0.51-0.89), but not in male patients (IRR 0.87, 95% CI 0.70-1.08). Conclusions: Among non-valvular atrial fibrillation patients who were taking DOACs, concurrent use of statins decreased major bleeding risk, including intracerebral hemorrhage and gastrointestinal tract bleeding. Considering this and other cardioprotective effects, statins should be considered in all eligible patients prescribed with DOACs.
RESUMO
Graft-versus-host disease (GvHD) is a major complication after allogeneic hematopoietic cell transplantation (HCT). Current strategies to prevent GvHD with immunosuppressive drugs carry significant morbidity and may affect the graft-versus-tumor (GVT) effect. Inflammatory bowel disease (IBD) is an intestinal inflammatory condition that affects more than 2 million people in the United States. Current strategies to prevent colitis with immunosuppressive drugs carry significant morbidity. Recently, Repulsive Guidance Molecule b (RGMb) has been identified as part of a signaling hub with neogenin and BMP receptors in mice and humans. In addition, RGMb binds BMP-2/4 in mice and humans as well as PD-L2 in mice. RGMb is expressed in the gut epithelium and by antigen presenting cells, and we found significantly increased expression in mouse small intestine after total body irradiation HCT conditioning. We hypothesized that RGMb may play a role in GvHD and IBD pathogenesis by contributing to mucosal inflammation. Using major-mismatched HCT mouse models, treatment with an anti-RGMb monoclonal antibody (mAb) that blocks the interaction with BMP-2/4 and neogenin prevented GvHD and improved survival compared to isotype control (75% versus 30% survival at 60 days after transplantation). The GVT effect was retained in tumor models. Using an inflammatory bowel disease dextran sulfate sodium model, treatment with anti-RGMb blocking monoclonal antibody but not isotype control prevented colitis and improved survival compared to control (73% versus 33% at 21 days after treatment) restoring gut homeostasis. Anti-RGMb mAb (9D1) treatment decreased IFN-γ and significantly increased IL-5 and IL-10 in the gut of the treated mice compared to the isotype control treated mice.
Assuntos
Colite , Doença Enxerto-Hospedeiro , Doenças Inflamatórias Intestinais , Humanos , Camundongos , Animais , Inflamação , Doenças Inflamatórias Intestinais/terapia , Colite/induzido quimicamente , Imunossupressores , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Moléculas de Adesão Celular NeuronaisRESUMO
Hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection in comparison with single HBV infection causes more severe liver disease in nonuremic population. The long-term impact of HBV/HCV coinfection on severity of liver diseases and patient survival in hemodialysis patients is unclear. Forty-eight HBV-positive patients and 19 HBV/HCV-positive patients were followed up from February 1996 to September 2006. During 10-year follow-up, there was no difference in acute hepatitis episodes, abnormal serum alanine aminotransferase period, occurrence of cirrhosis and hepatocellular carcinoma, and patient survival between the two groups. The serum HBV DNA levels in HBV/HCV-positive patients were significantly lower than those in HBV-positive patients during the first 27-month follow-up. In conclusion, HCV infection suppresses the serum HBV DNA level in hemodialysis patients. Nevertheless, HBV/HCV coinfection in comparison with single HBV infection does not cause more severe liver diseases or reduce patient survival in hemodialysis patients during 10-year follow-up.
Assuntos
Hepacivirus/crescimento & desenvolvimento , Vírus da Hepatite B/crescimento & desenvolvimento , Hepatite B Crônica/terapia , Hepatite C Crônica/terapia , Diálise Renal , Adulto , Alanina Transaminase/sangue , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Antígenos Virais/sangue , Antígenos Virais/imunologia , Feminino , Seguimentos , Hepacivirus/imunologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica/complicações , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/mortalidade , Hepatite B Crônica/virologia , Hepatite C Crônica/complicações , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/mortalidade , Hepatite C Crônica/virologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , TaiwanRESUMO
The adverse impact of Coronavirus disease 2019 (COVID-19) on kidney function has been reported since the global pandemic. The burden of COVID-19 on kidney transplant recipients, however, has not been systematically analyzed. A systematic review and meta-analysis with a random-effect model was conducted to explore the rate of mortality, intensive care unit admission, invasive mechanical ventilation, acute kidney injury, kidney replacement therapy and graft loss in the adult kidney transplant population with COVID-19. Sensitivity analysis, subgroup analysis and meta-regression were also performed. Results: we demonstrated a pooled mortality rate of 21% (95% CI: 19-23%), an intensive care unit admission rate of 26% (95% CI: 22-31%), an invasive ventilation rate among those who required intensive care unit care of 72% (95% CI: 62-81%), an acute kidney injury rate of 44% (95% CI: 39-49%), a kidney replacement therapy rate of 12% (95% CI: 9-15%), and a graft loss rate of 8% (95% CI: 5-15%) in kidney transplant recipients with COVID-19. The meta-regression indicated that advancing age is associated with higher mortality; every increase in age by 10 years was associated with an increased mortality rate of 3.7%. Regional differences in outcome were also detected. Further studies focused on treatments and risk factor identification are needed.
RESUMO
Background: Functional connectivity detected by resting-state functional MRI (R-fMRI) helps to discover the subtle changes in brain activities. Patients with end-stage renal disease (ESRD) on hemodialysis (HD) have impaired brain networks. However, the functional changes of brain networks in patients with ESRD undergoing peritoneal dialysis (PD) have not been fully delineated, especially among those with preserved cognitive function. Therefore, it is worth knowing about the brain functional connectivity in patients with PD by using R-fMRI. Methods: This case-control study prospectively enrolled 19 patients with ESRD receiving PD and 24 age- and sex- matched controls. All participants without a history of cognitive decline received mini-mental status examination (MMSE) and brain 3-T R-fMRI. Comprehensive R-fMRI analyses included graph analysis for connectivity and seed-based correlation networks. Independent t-tests were used for comparing the graph parameters and connectivity networks between patients with PD and controls. Results: All subjects were cognitively intact (MMSE > 24). Whole-brain connectivity by graph analysis revealed significant differences between the two groups with decreased global efficiency (Eglob, p < 0.05), increased betweenness centrality (BC) (p < 0.01), and increased characteristic path length (L, p < 0.01) in patients with PD. The functional connections of the default-mode network (DMN), sensorimotor network (SMN), salience network (SN), and hippocampal network (HN) were impaired in patients with PD. Meanwhile, in DMN and SN, elevated connectivity was observed in certain brain regions of patients with PD. Conclusion: Patients with ESRD receiving PD had specific disruptions in functional connectivity. In graph analysis, Eglob, BC, and L showed significant connectivity changes compared to the controls. DMN and SN had the most prominent alterations among the observed networks, with both decreased and increased connectivity regions. Our study confirmed that significant changes in cerebral connections existed in cognitively intact patients with PD.
RESUMO
Over-immunosuppressed kidney transplant recipients are susceptible to malignancies and BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN). This study aimed to verify the association between BKPyV infection and urinary tract cancers (UTC). A total of 244 kidney transplant recipients were enrolled at Chang Gung Memorial Hospital from June 2000 to February 2020. Biopsy-proven BKPyVAN patients (n = 17) had worse kidney function (eGFR: 26 ± 13.7 vs. 47.8 ± 31.0 mL/min/1.73 m2). The 5-year allograft survival rates for patients with and without BKPyVAN were 67% and 93%, respectively (p = 0.0002), while the 10-year patient survival was not different between the two groups. BKPyVAN patients had a significantly higher incidence of UTC compared to the non-BKPyVAN group (29.4% vs. 6.6%). Kaplan-Meier analysis showed that the UTC-free survival rate was significantly lower in BKPyVAN patients, and the onset of UTC was significantly shorter in BKPyVAN patients (53.4 vs. 108.9 months). The multivariate logistic regression analysis demonstrated that age (RR = 1.062) and BKVAN (RR = 6.459) were the most significant risk factors for the development of UTC. Our study demonstrates that BKPyVAN patients have greater allograft losses, higher incidence, a lower cancer-free survival rate, and an earlier onset with a higher relative risk of developing UTC compared to non-BKPyVAN patients.
Assuntos
Vírus BK/patogenicidade , Nefropatias/complicações , Nefropatias/virologia , Infecções por Polyomavirus/complicações , Infecções Tumorais por Vírus/complicações , Neoplasias Urológicas/epidemiologia , Neoplasias Urológicas/etiologia , Adulto , Idoso , China/epidemiologia , Feminino , Humanos , Terapia de Imunossupressão/efeitos adversos , Imunossupressores/efeitos adversos , Incidência , Nefropatias/epidemiologia , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Transplantados/estatística & dados numéricos , Transplante Homólogo/efeitos adversos , Neoplasias Urológicas/virologia , ViremiaRESUMO
Interleukin (IL)-17A is upregulated in several renal diseases and plays a crucial role in renal inflammation. However, it remains unclear how IL-17A contributes to renal fibrosis. Our result demonstrated that IL-17A expression was upregulated in the obstructed kidney of unilateral ureter obstruction (UUO) mice when compared to the contralateral control kidney. Inhibition of IL-17A functions by the intravenous administration of an anti-IL-17A receptor antibody (100 µg) 2 h prior to UUO and on post-UUO day 1 and 3 significantly reduced fibronectin expression in the UUO kidney. The addition of IL-17A (25-100 µg) to human renal proximal tubular cells or renal fibroblasts caused an increase in fibronectin production and extracellular signal-regulated kinase (ERK)1/2 activation, which were reduced upon pretreatment with the ERK inhibitor U0126. The level of phosphorylated (p)-ERK1/2 was increased in the UUO kidney, but reduced by the administration of the anti-IL-17A receptor antibody, verifying the importance of the ERK pathway in vivo. TGF-ß1 mRNA expression and protein were increased in the UUO kidney and in IL-17A-stimulated cultured cells. The administration of an anti-TGF-ß1 neutralizing antibody or TGF-ß1 receptor I inhibitor (SB431542) to cells abrogated the IL-17A-mediated increase of fibronectin production. IL-17A induced an increase in p-Smad2 and p-Smad3 expression at 7.5 min and 24 h and pretreatment with the anti-TGF-ß1 neutralizing antibody, and SB431542 reduced the IL-17A-stimulated increase of p-Smad2. Knockdown of Smad2 or Smad3 expression inhibited the IL-17A-enhanced production of fibronectin. These results suggest an essential role for the TGF-ß/Smad pathway in the IL-17A-mediated increase of fibronectin production. This study demonstrates that IL-17A contributes to the production of extracellular matrix, and targeting its associated signaling pathways could provide a therapeutic target for preventing renal fibrosis.
Assuntos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fibrose/metabolismo , Interleucina-17/metabolismo , Interleucina-17/farmacologia , Rim/metabolismo , Proteínas Smad/metabolismo , Animais , Benzamidas/farmacologia , Butadienos/farmacologia , Linhagem Celular , Citocinas/metabolismo , Dioxóis/farmacologia , Feminino , Fibroblastos , Fibronectinas/metabolismo , Fibrose/patologia , Humanos , Rim/patologia , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Nitrilas/farmacologia , Transdução de Sinais , Fator de Crescimento Transformador beta1/metabolismo , Obstrução Ureteral/patologia , Obstrução Ureteral/terapiaRESUMO
BACKGROUND: Stroke is prevalent in patients with chronic kidney disease (CKD) and is associated with high mortality, but the causes of death after stroke among different CKD stages are not well known. AIMS: We aimed to investigate whether the severity of CKD would impact on the causes of death after first-ever stroke. METHODS: This retrospective multicenter cohort study included stoke patients with CKD between 2007 and 2012. The cause of death and date of death were ascertained by linking the National Death Registry Database of Taiwan. Clinical outcomes, 1-month, and 1-year mortality rates, and major causes of death were compared according to five CKD stages (G1 to G5) in the ischemic and hemorrhagic stroke separately. RESULTS: Of these patients, 9,878 were first-ever ischemic stroke (IS) patients, and 1,387 were first-ever hemorrhagic stroke (HS) patients. Patients with CKD G5 had the highest one-year mortality rate with hazard ratio 5.28 [95%CI, 3.94-7.08] in IS and 3.03 [95%CI, 2.03-4.54] in HS when compared to G1 patients. Leading causes of one-year death after IS were stroke, cancer, and pneumonia in early (G1-3) CKD patients, while diabetes mellitus, CKD, and stroke itself contributed to the major mortality in CKD G5 patients. An inverse association between eGFR decrement and the proportion of deaths caused by stroke itself was observed in CKD G2-5 patients after IS. Stroke was the leading cause of one-year death among all CKD patients after HS. CONCLUSIONS: Asides from high mortality, late-stage CKD patients had different causes of death from early CKD patients after stroke. This study highlights the need to imply different treatment strategies in late-stage CKD post-stroke patients to improve their prognosis.
Assuntos
Acidente Vascular Cerebral Hemorrágico/epidemiologia , AVC Isquêmico/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Feminino , Taxa de Filtração Glomerular , Acidente Vascular Cerebral Hemorrágico/mortalidade , Humanos , Armazenamento e Recuperação da Informação , AVC Isquêmico/mortalidade , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologiaRESUMO
Preclinical studies have shown that persistent mixed chimerism is linked to acceptance of organ allografts without immunosuppressive (IS) drugs. Mixed chimerism refers to continued mixing of donor and recipient hematopoietic cells in recipient tissues after transplantation of donor cells. To determine whether persistent mixed chimerism and tolerance can be established in patients undergoing living donor kidney transplantation, we infused allograft recipients with donor T cells and hematopoietic progenitors after posttransplant lymphoid irradiation. In 24 of 29 fully human leukocyte antigen (HLA)-matched patients who had persistent mixed chimerism for at least 6 months, complete IS drug withdrawal was achieved without subsequent evidence of rejection for at least 2 years. In 10 of 22 HLA haplotype-matched patients with persistent mixed chimerism for at least 12 months, reduction of IS drugs to tacrolimus monotherapy was achieved. Withdrawal of tacrolimus during the second year resulted in loss of detectable chimerism and subsequent rejection episodes, unless tacrolimus therapy was reinstituted. Posttransplant immune reconstitution of naïve B cells and B cell precursors was more rapid than the reconstitution of naïve T cells and thymic T cell precursors. Robust chimerism was observed only among naïve T and B cells but not among memory T cells. No evidence of rejection was observed in all surveillance graft biopsies obtained from mixed chimeric patients withdrawn from IS drugs, and none developed graft-versus-host disease. In conclusion, persistent mixed chimerism established in fully HLA- or haplotype-matched patients allowed for complete or partial IS drug withdrawal without rejection.
Assuntos
Quimerismo , Imunossupressores/farmacologia , Transplante de Rim , Suspensão de Tratamento , Adulto , Linfócitos B/imunologia , Feminino , Sobrevivência de Enxerto/imunologia , Haplótipos/genética , Teste de Histocompatibilidade , Humanos , Isoantígenos/imunologia , Teste de Cultura Mista de Linfócitos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Linfócitos T/imunologia , Tacrolimo/farmacologia , Doadores de Tecidos , Resultado do Tratamento , Adulto JovemRESUMO
Background:Peritonitis is a serious complication after invasive procedures in patients undergoing peritoneal dialysis (PD). Most studies that have investigated peritonitis following invasive gynecologic procedures enrolled small patient populations. This study focuses on the clinical presentation, outcomes, and effects of prophylactic antibiotic use before invasive techniques.Methods:A retrospective study was conducted on patients who underwent invasive gynecologic procedures between 2005 and 2015 in a tertiary medical center. Eligible patients were identified and enrolled and their demographic data were collected. The use of prophylactic antibiotics and the outcomes of peritonitis were recorded.Results:Twenty-six gynecologic procedures were performed on 18 PD patients. Seven episodes of peritonitis occurred in 6 patients after invasive gynecologic procedures. Eleven procedures were preceded by prophylactic antibiotic treatment (6 oral cefadroxil, 1 oral cefuroxime, 1 oral clindamycin, 1 intravenous [IV] ceftriaxone, 1 IV ceftazidime, and 1 IV cefazolin). The pathogens were diverse (group B Streptococcus, group D Streptococcus, E. coli, and Enterococcus). All episodes of peritonitis were successfully treated using intraperitoneal antibiotics without recurrence, technique failure, or mortality. The odds ratio of peritonitis in the non-prophylaxis group was 20.29 (95% confidence interval 1.01 - 406.35, p = 0.0103).Conclusion:The use of prophylactic antibiotic treatment considerably reduced the risk of peritonitis after invasive gyne co logic procedures.