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1.
Int J Infect Dis ; 117: 56-64, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35081417

RESUMO

BACKGROUND: Controversy remains about the efficacy of tocilizumab (TCZ) for the treatment of severe COVID-19. We aimed to analyze the profile of TCZ-respondent patients. METHODS: We retrospectively analyzed a cohort of patients with severe COVID-19 who received off-label TCZ after recommendation by a local committee and were admitted to the University Hospital "12 de Octubre" until May 2020. The primary end point was a significant clinical improvement (SCI) on day 14 after administration of TCZ. Factors independently related to SCI were analyzed by multivariate logistic regression models. RESULTS: Of 428 (63.3%) patients treated with TCZ, 271 (63.3%) experienced SCI. After adjustment for factors related to unfavorable outcomes, TCZ administration within the first 48 hours from admission (odds ratio [OR]: 1.98, 95% confidence Interval [95% CI]: 1.1-3.55; P = 0.02) and ALT levels >100 UI/L at day 0 (OR: 3.28; 95% CI: 1.3-8.1; P = 0.01) were independently related to SCI. The rate of SCI significantly decreased according to the time of TCZ administration: 70.2% in the first 48 hours from admission, 58.5% on days 3-7, and 45.1% after day 7 (P = 0.03 and P = 0.001, respectively). CONCLUSION: TCZ improves the prognosis of patients with COVID-19 the most if treatment starts within the first 48 hours after admission.


Assuntos
COVID-19 , Anticorpos Monoclonais Humanizados , COVID-19/tratamento farmacológico , Humanos , Estudos Retrospectivos , SARS-CoV-2
2.
Transpl Infect Dis ; 24(1): e13771, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34921747

RESUMO

BACKGROUND: Increasing evidence suggests that infection with the nonpathogenic human pegivirus type 1 (HPgV-1) exerts a clinical benefit in human immunodeficiency virus (HIV) patients, which could be attributable to immunomodulatory effects. Whether this impact can be extrapolated to kidney transplantation (KT) remains largely unknown. METHODS: We measured plasma HPgV-1 RNA by real-time polymerase chain reaction targeting the 5' untranslated region at various points (pretransplantation, day 7, months 1, 3, 6, and 12) in 199 KT recipients. Study outcomes included posttransplant serious infection, immunosuppression-related adverse event (opportunistic infection and/or de novo cancer), and acute graft rejection. RESULTS: HPgV-1 infection was demonstrated in 52 (26.1%) patients, with rates increasing from 14.7% at baseline to 19.1% by month 12 (p-value = .071). De novo infection occurred in 13.8% of patients with no detectable HPgV-1 RNA before transplantation. Double-organ (liver-kidney or kidney-pancreas) transplantation (odds ratio [OR]: 5.62; 95% confidence interval [CI]: 1.52-20.82) and donation after brain death (OR: 2.21; 95% CI: 1.00-4.88) were associated with posttransplant HPgV-1 infection, whereas pretransplant hypertension was protective (OR: 0.23; 95% CI: 0.09-0.55). There were no significant differences in the incidence of study outcomes according to HPgV-1 status. Plasma HPgV-1 RNA levels at different points did not significantly differ between patients that subsequently developed outcomes and those remaining free from these events. No correlation between HPgV-1 RNA and immune parameters or torque teno virus DNA load was observed either. CONCLUSION: Unlike patients living with HIV, HPgV-1 infection does not seem to influence patient or graft outcomes after KT.


Assuntos
Infecções por Flaviviridae , Vírus GB C , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Cinética , Transplantados
3.
Transplant Direct ; 7(12): e794, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34805496

RESUMO

Severe acute respiratory syndrome coronavirus 2-specific cell-mediated immunity (SARS-CoV-2-CMI) elicited by mRNA-based vaccines in solid organ transplant (SOT) recipients and its correlation with antibody responses remain poorly characterized. METHODS: We included 44 (28 kidney, 14 liver, and 2 double organ) recipients who received the full series of the mRNA-1273 vaccine. SARS-CoV-2-CMI was evaluated at baseline, before the second dose, and at 2 wk after completion of vaccination by an ELISpot-based interferon-γ FluoroSpot assay using overlapping peptides covering the S1 domain. SARS-CoV-2 immunoglobulin G seroconversion and serum neutralizing activity against the spike protein were assessed at the same points by commercial ELISA and an angiotensin-converting enzyme-2/spike antibody inhibition method, respectively. Postvaccination SARS-CoV-2-CMI was compared with 28 healthcare workers who received the BNT162b2 vaccine. RESULTS: Positive SARS-CoV-2-CMI increased from 6.8% at baseline to 23.3% after the first mRNA-1273 dose and 59.5% after the completion of vaccination (P < 0.0001). Lower rates were observed for immunoglobulin G seroconversion (2.3%, 18.6%, and 57.1%, respectively) and neutralizing activity (2.3%, 11.6%, and 31.0%). There was a modest correlation between neutralizing titers and the magnitude of SARS-CoV-2-CMI (Spearman's rho: 0.375; P = 0.015). Fifteen recipients (35.7%) mounted SARS-CoV-2-CMI without detectable neutralizing activity, whereas 3 (7.1%) did the opposite, yielding poor categorical agreement (Kappa statistic: 0.201). Rates of positive SARS-CoV-2-CMI among SOT recipients were significantly decreased compared with nontransplant controls (82.1% and 100.0% after the first dose and completion of vaccination, respectively; P < 0.0001). Kidney transplantation, the use of tacrolimus and prednisone, and the number of immunosuppressive agents were associated with lower cell-mediated responses. Results remained unchanged when 3 recipients with prevaccination SARS-CoV-2-CMI were excluded. CONCLUSIONS: Two-thirds of SOT recipients mounted SARS-CoV-2-CMI following vaccination with mRNA-1273. Notable discordance was observed between vaccine-induced cell-mediated and neutralizing humoral immunities. Future studies should determine whether these patients with incomplete responses are effectively protected.

4.
Med Clin (Barc) ; 2021 Jun 18.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34243954

RESUMO

BACKGROUND: The effect of immunomodulatory therapy with tocilizumab for coronavirus disease 2019 (COVID-19) in real-life clinical practice remains controversial. METHODS: Single-center retrospective matched cohort analysis including 47 consecutive patients treated with intravenous tocilizumab for severe COVID-19 pneumonia ("TCZ group"), matched by age, comorbidities, time from symptoms onset and baseline SpO2/FiO2 ratio with 47 patients receiving standard of care alone ("SoC group"). RESULTS: There were no significant differences between the TCZ and SoC groups in the rate of clinical improvement (hospital discharge and/or a decrease of ≥2 points on a six-point ordinal scale) by day 7 (51.1% [24/47] versus 48.9% [23/47]; P-value=1.000). No differences were observed at day 14 in terms of clinical improvement (72.3% versus 76.6%; P-value=0.791), all-cause mortality (10.6% versus 12.8%; P-value=1.000), and the composite of invasive mechanical ventilation and/or death (25.5% versus 23.4%; P-value=1.000) either. Patients in the TCZ group had a more rapid normalization of C-reactive protein levels. CONCLUSIONS: No apparent benefit was observed in patients with severe COVID-19 treated with tocilizumab as compared to a matched retrospective cohort.

5.
Am J Transplant ; 21(8): 2785-2794, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34092033

RESUMO

Whether immunosuppression impairs severe acute respiratory syndrome coronavirus 2-specific T cell-mediated immunity (SARS-CoV-2-CMI) after liver transplantation (LT) remains unknown. We included 31 LT recipients in whom SARS-CoV-2-CMI was assessed by intracellular cytokine staining (ICS) and interferon (IFN)-γ FluoroSpot assay after a median of 103 days from COVID-19 diagnosis. Serum SARS-CoV-2 IgG antibodies were measured by ELISA. A control group of nontransplant immunocompetent patients were matched (1:1 ratio) by age and time from diagnosis. Post-transplant SARS-CoV-2-CMI was detected by ICS in 90.3% (28/31) of recipients, with higher proportions for IFN-γ-producing CD4+ than CD8+ responses (93.5% versus 83.9%). Positive spike-specific and nucleoprotein-specific responses were found by FluoroSpot in 86.7% (26/30) of recipients each, whereas membrane protein-specific response was present in 83.3% (25/30). An inverse correlation was observed between the number of spike-specific IFN-γ-producing SFUs and time from diagnosis (Spearman's rho: -0.418; p value = .024). Two recipients (6.5%) failed to mount either T cell-mediated or IgG responses. There were no significant differences between LT recipients and nontransplant patients in the magnitude of responses by FluoroSpot to any of the antigens. Most LT recipients mount detectable-but declining over time-SARS-CoV-2-CMI after a median of 3 months from COVID-19, with no meaningful differences with immunocompetent patients.


Assuntos
COVID-19 , Transplante de Fígado , Anticorpos Antivirais , Teste para COVID-19 , Humanos , Transplante de Fígado/efeitos adversos , SARS-CoV-2 , Linfócitos T , Transplantados
6.
Transpl Infect Dis ; 23(4): e13597, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33751753

RESUMO

BACKGROUND: Immunomodulatory effects attributable to cytomegalovirus (CMV) would predispose to BK polyomavirus (BKPyV) infection after kidney transplantation (KT), although available evidence is conflicting. It has been suggested that (val)ganciclovir therapy may increase the risk of BKPyV viremia and BKPyV-associated nephropathy (BKPyVAN) as a result of drug-induced T-cell impairment. METHODS: We investigated whether CMV replication and/or (val)ganciclovir exposure (either as prophylaxis or treatment) were associated with the development of BKPyV viremia or BKPyVAN in a prospective cohort of 399 KT recipients. CMV infection (any level or high-level viremia and area under the curve of DNAemia) and (val)ganciclovir exposure (any duration of therapy and cumulative days of treatment) during the first post-transplant year were explored through separate landmark survival analyses. RESULTS: Cumulative incidence of BKPyV viremia and BKPyVAN after a median follow-up of 551 days was 23.1% and 2.5%, respectively. One-year rates of CMV infection and (val)ganciclovir therapy were 47.4% and 54.1%, respectively. No differences were observed in BKPyV viremia- or BKPyVAN-free survival according to previous CMV infection or (val)ganciclovir exposure in any of the landmark analyses. Adjusted Cox models confirmed this lack of association. CONCLUSION: Our findings do not confirm the existence of a relevant impact of CMV infection or (val)ganciclovir therapy on the risk of post-transplant BKPyV events.


Assuntos
Vírus BK , Infecções por Citomegalovirus , Transplante de Rim , Nefrite Intersticial , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Antivirais/efeitos adversos , Infecções por Citomegalovirus/epidemiologia , Ganciclovir/efeitos adversos , Humanos , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/epidemiologia , Estudos Prospectivos , Valganciclovir , Viremia/epidemiologia
7.
Transplantation ; 105(6): 1372-1380, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33729741

RESUMO

BACKGROUND: The magnitude and kinetics of severe acute respiratory syndrome coronavirus 2-specific cell-mediated immunity (SARS-CoV-2-CMI) in kidney transplant (KT) recipients remain largely unknown. METHODS: We enumerated SARS-CoV-2-specific interferon-γ-producing CD69+ CD4+ and CD8+ T cells at months 4 and 6 from the diagnosis of coronavirus disease 2019 (COVID-19) in 21 KT recipients by intracellular cytokine staining. Overlapping peptides encompassing the SARS-CoV-2 spike (S) glycoprotein N-terminal 1- to 643-amino acid sequence and the membrane protein were used as stimulus. SARS-CoV-2 IgG antibodies targeting the S1 protein were assessed by ELISA at month 6. RESULTS: Detectable (≥0.1%) SARS-CoV-2-specific CD4+ T-cell response was found in 57.1% and 47.4% of patients at months 4 and 6. Corresponding rates for CD8+ T cells were 19.0% and 42.1%, respectively. Absolute SARS-CoV-2-specific T-cell counts increased from month 4 to month 6 in CD8+ (P = 0.086) but not CD4+ subsets (P = 0.349). Four of 10 patients with any detectable response at month 4 had lost SARS-CoV-2-CMI by month 6, whereas 5 of 9 patients mounted SARS-CoV-2-CMI within this period. All but 2 patients (89.5%) tested positive for SARS-CoV-2 IgG. Patients lacking detectable SARS-CoV-2-specific CD4+ response by month 6 were more likely to be under tacrolimus (100.0% versus 66.7%; P = 0.087) and to have received tocilizumab for the previous COVID-19 episode (40.0% versus 0.0%; P = 0.087). CONCLUSIONS: Although still exploratory and limited by small sample size, the present study suggests that a substantial proportion of KT recipients exhibited detectable SARS-CoV-2-CMI after 6 months from COVID-19 diagnosis.


Assuntos
COVID-19/imunologia , Imunidade Celular , Hospedeiro Imunocomprometido , Transplante de Rim/efeitos adversos , SARS-CoV-2/imunologia , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , Teste para COVID-19 , Feminino , Seguimentos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/efeitos adversos , Interferon gama/metabolismo , Masculino , Pessoa de Meia-Idade , Transplantados
8.
Transpl Int ; 35: 10273, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35185374

RESUMO

Previous reports hypothesized that cytomegalovirus (CMV) may predispose to non-CMV infection after kidney transplantation (KT). We analysed the incidence of non-CMV infection (overall, bacterial and opportunistic) in 291 KT recipients according to the previous development of any level or high-level (≥1,000 IU/ml) CMV viremia. Exposure to CMV replication was assessed throughout fixed intervals covering first the 30, 90, 180 and 360 post-transplant days (cumulative exposure) and non-overlapping preceding periods (recent exposure). Adjusted Cox models were constructed for each landmark analysis. Overall, 67.7 and 50.5% patients experienced non-CMV and CMV infection, respectively. Patients with cumulative CMV exposure had higher incidence of non-CMV infection beyond days 30 (p-value = 0.002) and 90 (p-value = 0.068), although these associations did not remain after multivariable adjustment. No significant associations were observed for the remaining landmark models (including those based on high-level viremia or recent CMV exposure), or when bacterial and opportunistic infection were separately analysed. There were no differences in viral kinetics (peak CMV viremia and area under curve of CMV viral load) either. Our findings do not support the existence of an independent association between previous CMV exposure and the overall risk of post-transplant infection, although results might be affected by power limitations.


Assuntos
Infecções por Citomegalovirus , Transplante de Rim , Antivirais , Estudos de Coortes , Citomegalovirus , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/etiologia , Humanos , Transplante de Rim/efeitos adversos , Carga Viral , Replicação Viral
9.
J Infect Dis ; 222(3): 479-487, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32112085

RESUMO

BACKGROUND: We aimed at constructing a composite score based on Epstein-Barr virus DNAemia (EBVd) and simple clinical and immunological parameters to predict late severe infection (LI) beyond month 6 in solid organ transplantation (SOT) recipients. METHODS: Kidney and liver transplant recipients between May 2014 and August 2016 at 4 participating centers were included. Serum immunoglobulins and complement factors, peripheral blood lymphocyte subpopulations, and whole blood EBVd were determined at months 1, 3, and 6. Cox regression analyses were performed to generate a weighted score for the prediction of LI. RESULTS: Overall, 309 SOT recipients were followed-up for a median of 1000 days from transplant (interquartile range, 822-1124). Late severe infection occurred in 104 patients (33.6%). The CLIV Score consisted of the following variables at month 6: high-level EBVd (>1500 IU/mL) and recurrent infection during the previous months (6 points); recipient age ≥70 years and chronic graft dysfunction (5 points); cytomegalovirus mismatch (4 points); and CD8+ T-cell count <400 cells/µL (2 points). The area under receiver operating characteristics curve was 0.77 (95% confidence interval, 0.71-0.84). The risk of LI at day 1000 was as follows: score 0, 12.6%; score 2-5, 25.5%; score 6-9, 52.7%; score ≥10, 73.5%. CONCLUSIONS: While waiting for further external validation, the CLIV Score based on clinical and immune-virological parameters is potentially useful to stratify the risk of LI after SOT.


Assuntos
Infecções por Vírus Epstein-Barr/diagnóstico , Herpesvirus Humano 4/isolamento & purificação , Infecções Oportunistas/etiologia , Transplante de Órgãos/efeitos adversos , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Linfócitos T CD8-Positivos/imunologia , DNA Viral/sangue , Infecções por Vírus Epstein-Barr/virologia , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Curva ROC
10.
Am J Transplant ; 20(8): 2070-2080, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31991045

RESUMO

Monitoring for cytomegalovirus (CMV)-specific cell-mediated immunity (CMV-CMI) may be useful for individualizing valganciclovir (VGCV) prophylaxis after kidney transplantation (KT). We performed a commercial ELISA-based interferon (IFN)-γ release assay (QTF-CMV) from posttransplant months 2-5 (362 points) in 120 CMV-seropositive KT recipients that received antithymocyte globulin as induction therapy and VGCV prophylaxis (median of 92 days). Forty-seven patients (39.3%) had CMV infection after discontinuation of prophylaxis. The QTF-CMV assay was reactive, nonreactive, and indeterminate in 264 (72.9%), 90 (24.9%), and 8 points (2.2%). The QTF-CMV assay at prophylaxis discontinuation exhibited suboptimal accuracy for predicting protective CMV-CMI (sensitivity: 77.4%; specificity: 34.3%; positive predictive value [PPV]: 64.1%; negative predictive value [NPV]: 50.0%), with no differences in 1-year CMV infection rates between patients with negative (nonreactive or indeterminate) or reactive results (45.8% vs 36.1%; P = .244). Specificity and PPV to predict protective CMV-CMI improved by elevating the IFN-γ cutoff value to 1.13 IU/mL (65.7% and 71.4%) and 7.0 IU/mL (85.7% and 76.2%), although NPVs decreased. The QTF-CMV assay as per manufacturer's interpretative criteria performed poorly to predict protection from CMV infection following discontinuation of VGCV prophylaxis among ATG-treated CMV-seropositive KT recipients. This performance is slightly improved by modifying the IFN-γ positivity threshold.


Assuntos
Infecções por Citomegalovirus , Transplante de Rim , Soro Antilinfocitário/uso terapêutico , Antivirais/uso terapêutico , Citomegalovirus , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/prevenção & controle , Ensaio de Imunoadsorção Enzimática , Humanos , Imunidade Celular , Testes de Liberação de Interferon-gama , Transplante de Rim/efeitos adversos , Transplantados
12.
J Clin Microbiol ; 57(2)2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30463889

RESUMO

The objective of the present study was to evaluate the value of the PCR cycle threshold (CT ) for predicting the recurrence/severity of infection compared to that of toxin detection plus clinical variables. First episodes of Clostridium difficile infection (CDI) diagnosed during 2015 at our institution were included. Samples were tested for glutamate dehydrogenase (GDH) and toxin A/B by use of a single enzyme immunoassay (EIA). The Xpert C. difficile PCR assay was performed on GDH-positive samples. Medical data were reviewed by investigators blinded to diagnostic results for comparison of patients with and without recurrence or a poor outcome (severe/severe-complicated CDI episodes and all-cause death). We generated two sets of predictive models by incorporating the presence of a positive toxin EIA ("EIA-including model") or the optimal PCR CT cutoff value ("PCR-including model") into the clinical variables. Among 227 episodes of CDI included in the study, the rates of recurrence and poor outcome were 15.8% and 30.8%, respectively. The mean PCR CT was lower for episodes with recurrence (24.00 ± 3.28 versus 26.02 ± 4.54; P = 0.002) or a poor outcome (24.9 ± 4.24 versus 26.05 ± 4.47; P = 0.07). The optimal cutoff value for recurrence was 25.65 (sensitivity, 77.8% [95% confidence interval {CI}, 60.9 to 89.9]; and specificity, 46.6% [95% CI, 39.4 to 53.9]). The area under the receiver operator characteristics curve (auROC) for the "PCR-including model" was similar to that for the "EIA-including model" (0.785 versus 0.775, respectively). The optimal PCR CT value for poor outcome was 27.55 (sensitivity, 78.6% [95% CI, 67.1 to 87.5]; and specificity, 35.7% [95% CI, 28.2 to 43.7]). The auROC of the "PCR-including model" was again similar to that of the "EIA-including model" (0.804 versus 0.801). Despite the inverse correlation between PCR CT and the risk of CDI recurrence/severity, this determination does not meaningfully increase the predictive value of clinical variables plus toxin EIA.


Assuntos
Proteínas de Bactérias/genética , Toxinas Bacterianas/genética , Regras de Decisão Clínica , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/patologia , Reação em Cadeia da Polimerase/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Técnicas Imunoenzimáticas/métodos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Recidiva , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento , Adulto Jovem
13.
Am J Transplant ; 19(4): 1139-1149, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30346659

RESUMO

The replication kinetics of nonpathogenic anelloviruses belonging to the Alphatorquevirus genus (such as torque teno virus) might reflect the overall state of posttransplant immunosuppression. We analyzed 221 kidney transplant (KT) recipients in whom plasma alphatorquevirus DNA load was quantified by real-time polymerase chain reaction at baseline and regularly through the first 12 posttransplant months. Study outcomes included posttransplant infection and a composite of opportunistic infection and/or de novo malignancy (immunosuppression-related adverse event [iRAE]). Alphatorquevirus DNA loads at month 1 were higher among patients who subsequently developed posttransplant infection (P  = .023) or iRAE (P  = .009). Likewise, those with iRAE beyond months 3 and 6 also exhibited higher peak viral loads over the preceding periods. Areas under the curve for log10 alphatorquevirus DNAemia estimated by months 1 or 6 were significantly higher in patients experiencing study outcomes. Alphatorquevirus DNA loads above 3.15 and 4.56 log10 copies/mL at month 1 predicted the occurrence of posttransplant infection (adjusted hazard ratio [aHR]: 2.88; 95% confidence interval [CI]: 1.13-7.36; P  = .027) and iRAE (aHR: 5.17; 95% CI: 2.01-13.33; P  = .001). In conclusion, posttransplant monitoring of plasma alphatorquevirus DNA kinetics may be useful to identify KT recipients at increased risk of immunosuppression-related complications.


Assuntos
Anelloviridae/genética , DNA Viral/metabolismo , Imunossupressores/efeitos adversos , Transplante de Rim , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
14.
Transpl Infect Dis ; 20(6): e12988, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30187601

RESUMO

BACKGROUND: Recent studies have reported an increased susceptibility to infection among vitamin D-deficient kidney transplant (KT) recipients, although methodological concerns remain. METHODS: Serum 25-hydroxyvitamin D (25(OH)D) levels were measured in 246 KT recipients at post-transplant months 1, 3, 6 and 12. Vitamin D status was analysed in terms of deficiency (Endocrine Society [<20 ng/mL] and Institute of Medicine [IoM, <12 ng/mL] criteria) and as a continuous variable. Cox models for overall, bacterial and opportunistic infection were adjusted for nutritional status and immunosuppression-related covariates. RESULTS: Median serum 25(OH)D increased from month 1 (10.5 ng/mL) to month 6 (16.3 ng/mL; P-value = 0.001). Prevalence of vitamin D deficiency at month 1 ranged from 87.0% to 61.0% (depending on the diagnostic criteria) and significantly decreased over the next months. After adjustment for age and nutritional status, vitamin D deficiency (serum 25(OH)D < 12 ng/mL) at month 1 was an independent risk factor for overall (hazard ratio [HR]: 1.70; 95% confidence interval [CI]: 1.08-2.69; P-value = 0.023) and opportunistic infection (HR: 4.05; 95% CI: 1.57-10.46; P-value = 0.004), but not for bacterial infection. A protective effect for overall (adjusted HR: 0.76; 95% CI: 0.63-0.93; P-value = 0.007) and opportunistic infection (adjusted HR: 0.62; 95% CI: 0.45-0.86; P-value = 0.004) was observed when 25(OH)D levels were analyzed per one-quartile increases. CONCLUSIONS: Vitamin D status influences the risk of infection among KT recipients, with the association being particularly evident for opportunistic events and mainly restricted to the early post-transplant period.


Assuntos
Suscetibilidade a Doenças/sangue , Infecções/epidemiologia , Transplante de Rim/efeitos adversos , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Adulto , Idoso , Feminino , Humanos , Infecções/microbiologia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologia , Fatores de Tempo , Vitamina D/sangue , Deficiência de Vitamina D/sangue
15.
Atherosclerosis ; 269: 204-210, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29407595

RESUMO

BACKGROUND AND AIMS: Cardiovascular disease (CVD) is a leading cause of mortality after kidney transplantation (KT). The potential role of the complement system in the pathogenesis of post-transplant CVD remains unexplored. METHODS: Serum complement (C3 and C4) levels were measured at baseline and post-transplant months 1 and 6 in 447 kT recipients. The study outcome was post-transplant atherothrombotic event (PAE), a composite of acute coronary syndrome, critical peripheral arterial disease, stroke and/or transient ischemic attack. RESULTS: After a median follow-up of 4.2 years, 48 PAEs occurred in 43 patients (cumulative incidence: 9.6%; incidence rate: 2.6 events per 100 transplant-years). No differences were found in C3 and C4 levels at baseline or month 1 between patients with or without PAE. However, C3 levels at month 6 were significantly lower in patients developing PAE beyond that point (i.e., late PAE) (96.9 ±â€¯22.3 vs. 109.6 ±â€¯24.0 mg/dL; p = 0.013). The presence of C3 hypocomplementemia at month 6 was associated with a lower PAE-free survival (p = 0.002). After adjusting for conventional CVD risk factors and acute graft rejection, C3 hypocomplementemia at month 6 remained as an independent risk factor for late PAE in all the exploratory models (minimum hazard ratio: 3.24; p = 0.011). With respect to a model exclusively based on clinical variables, the inclusion of C3 levels at month 6 improved predictive capacity (areas under ROC curves: 0.788 and 0.812, respectively). CONCLUSIONS: Post-transplant monitoring of serum C3 levels might be useful to identify KT recipients at increased risk of CVD.


Assuntos
Doenças Cardiovasculares/imunologia , Complemento C3/deficiência , Complemento C4/deficiência , Transplante de Rim/efeitos adversos , Adulto , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Monitorização Imunológica , Intervalo Livre de Progressão , Estudos Prospectivos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Espanha/epidemiologia , Fatores de Tempo
16.
Transpl Infect Dis ; 20(1)2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29120522

RESUMO

BACKGROUND: The liver-synthesized peptide hepcidin is a key regulator of iron metabolism and correlates with total iron stores. We analyzed the association between pre-transplant hepcidin-25 levels and infection after kidney transplantation (KT). METHODS: Serum hepcidin-25 levels were measured at baseline by high-sensitivity ELISA in 91 patients undergoing KT at our institution between December 2011 and March 2013. The impact of this biomarker on the incidence of post-transplant infection (excluding lower urinary tract infection) during the first year was assessed by Cox regression. RESULTS: Mean hepcidin-25 level was 82.3 ± 67.4 ng/mL and strongly correlated with serum ferritin (Spearman's rho = 0.703; P < .001). There were no significant differences in hepcidin-25 levels between patients with or without overall infection (96.4 ± 67.5 vs 72.6 ± 66.7 ng/mL; P = .101). Such difference was evident for opportunistic (128.9 ± 75.0 vs 73.0 ± 62.3 ng/mL; P = .003) and, to a lesser extent, surgical-site infection (107.5 ± 73.3 vs 76.5 ± 65.2 ng/mL; P = .087). Patients with hepcidin-25 levels ≥72.5 ng/mL had higher 12-month cumulative incidence of overall infection (51.2% vs 29.2%; P = .032). After multivariate adjustment, hepcidin-25 ≥72.5 ng/mL acted as an independent risk factor for overall (adjusted hazard ratio [aHR] 3.86; 95% confidence interval [CI] 1.49-9.96; P = .005) and opportunistic infection (aHR 4.32; 95% CI 1.18-15.75; P = .027). CONCLUSION: Elevated baseline serum hepcidin-25 levels were associated with increased risk of infection after KT, suggesting a role for iron overload in the individual susceptibility to post-transplant infection.


Assuntos
Infecções Bacterianas/etiologia , Hepcidinas/sangue , Sobrecarga de Ferro/sangue , Ferro/sangue , Transplante de Rim/efeitos adversos , Adulto , Idoso , Infecções Bacterianas/microbiologia , Biomarcadores , Ensaio de Imunoadsorção Enzimática , Feminino , Ferritinas/sangue , Humanos , Incidência , Ferro/metabolismo , Sobrecarga de Ferro/etiologia , Fígado , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/etiologia , Infecções Oportunistas/microbiologia , Fatores de Risco , Transplantados , Infecções Urinárias
17.
Transpl Int ; 31(2): 187-197, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28940695

RESUMO

Despite its impact on quality of life and potential for complications, specific risk and protective factors for herpes zoster (HZ) after kidney transplantation (KT) remain to be clarified. We included 444 patients undergoing KT between November 2008 and March 2013. Peripheral blood lymphocyte subpopulations were measured at baseline and months 1 and 6. The risk factors for early (first post-transplant year) and late HZ (years 1-5) were separately assessed. We observed 35 episodes of post-transplant HZ after a median follow-up of 48.3 months (incidence rate: 0.057 per 1000 transplant-days). Median interval from transplantation was 18.3 months. Six patients (17.1%) developed disseminated infection. Postherpetic neuralgia occurred in 10 cases (28.6%). The receipt of anti-cytomegalovirus (CMV) prophylaxis with (val)ganciclovir decreased the risk of early HZ [adjusted hazard ratio (aHR): 0.08; 95% CI: 0.01-1.13; P-value = 0.062], whereas the natural killer (NK) cell at month 6 was protective for the occurrence of late HZ [aHR (per 10-cells/µl increase): 0.94; 95% CI: 0.88-1.00; P-value = 0.054]. In conclusion, two easily ascertainable factors (whether the patient is receiving anti-CMV prophylaxis and the NK cell count at month 6) might be potentially useful to tailor preventive strategies according to individual susceptibility to post-transplant HZ.


Assuntos
Antivirais/administração & dosagem , Infecções por Citomegalovirus/prevenção & controle , Ganciclovir/administração & dosagem , Herpes Zoster/prevenção & controle , Transplante de Rim/métodos , Transplantados , Adulto , Idoso , Quimioprevenção/métodos , Estudos de Coortes , Citomegalovirus/efeitos dos fármacos , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/tratamento farmacológico , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Células Matadoras Naturais/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Curva ROC , Estudos Retrospectivos , Medição de Risco
18.
Transpl Infect Dis ; 19(2)2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28122147

RESUMO

BACKGROUND: The transmembrane glycoprotein CD30 contributes to regulate the balance between Th1 and Th2 responses. Previous studies have reported conflicting results on the utility of its soluble form (sCD30) to predict post-transplant infection. METHODS: Serum sCD30 was measured by a commercial ELISA assay at baseline and post-transplant months 1, 3, and 6 in 100 kidney transplant (KT) recipients (279 monitoring points). The impact of sCD30 levels on the incidence of overall, bacterial and opportunistic infection during the first 12 months after transplantation was assessed by Cox regression. RESULTS: There were no differences in serum sCD30 according to the occurrence of overall or opportunistic infection. However, sCD30 levels were higher in patients with bacterial infection compared to those without at baseline (P=.038) and months 1 (P<.0001), 3 (P=.043), and 6 after transplantation (P=.006). Patients with baseline sCD30 levels ≥13.5 ng/mL had lower 12-month bacterial infection-free survival (35.0% vs 80.0%; P<.0001). After adjusting for potential confounders, baseline sCD30 levels ≥13.5 ng/mL remained as an independent risk factor for bacterial infection (adjusted hazard ratio [aHR]: 4.65; 95% confidence interval [CI]: 2.05-10.53; <.001). Analogously, sCD30 levels ≥6.0 ng/mL at month 1 acted as a risk factor for subsequent bacterial infection (aHR: 5.29; 95% CI: 1.11-25.14; P=.036). CONCLUSION: Higher serum sCD30 levels were associated with an increased risk of bacterial infection after KT. We hypothesize that this biomarker reflects a Th2 -polarized T-cell response, which exerts a detrimental effect on the immunity against bacterial pathogens.


Assuntos
Infecções Bacterianas/diagnóstico , Antígeno Ki-1/sangue , Transplante de Rim/efeitos adversos , Infecções Oportunistas/diagnóstico , Adulto , Idoso , Infecções Bacterianas/epidemiologia , Biomarcadores/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Rejeição de Enxerto/prevenção & controle , Humanos , Incidência , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/epidemiologia , Estudos Prospectivos , Análise de Regressão , Fatores de Risco , Taxa de Sobrevida
19.
Transpl Int ; 29(10): 1094-105, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27362817

RESUMO

The measurement of intracellular concentrations of adenosine triphosphate (iATP) in phytohemagglutinin-stimulated CD4(+) T cells constitutes a surrogate marker for post-transplant cell-mediated immunity (CMI). This assay has shown suboptimal accuracy for predicting infection after kidney transplantation (KT). We hypothesize that its predictive capacity depends on the specific contribution of the CMI to host-pathogen interactions. We assessed iATP levels in 100 KT recipients at baseline and months 1, 3, and 6 (363 measurements). No association was found between iATP at month 1 and the risk for overall or bacterial infection, although such association was evident for cytomegalovirus (CMV) disease (multivariate-adjusted hazard ratio [per 50-unit increment]: 0.83; P-value = 0.048). There were no significant differences in mean iATP between stable patients (319.4 ng/ml) and those developing overall (304.1 ng/ml) or bacterial infection (346.9 ng/ml) over the 45 days following monitoring. However, iATP was significantly lower in patients who developed CMV disease (223.5 ng/ml; P-values <0.002). The optimal cutoff (265 ng/ml) for predicting CMV disease in patients not receiving antiviral prophylaxis yielded sensitivity, specificity, positive, and negative predictive values of 85.7%, 68.3%, 15.2%, and 98.6%, respectively. In conclusion, a non-pathogen-specific monitoring of CMI by means of iATP informs the risk of CMV disease in KT recipients.


Assuntos
Trifosfato de Adenosina/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Infecções por Citomegalovirus/imunologia , Insuficiência Renal/cirurgia , Adulto , Idoso , Citomegalovirus , Feminino , Rejeição de Enxerto/prevenção & controle , Humanos , Sistema Imunitário , Imunidade Celular , Imunossupressores , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Curva ROC , Insuficiência Renal/complicações , Risco , Transplantados
20.
Infection ; 43(4): 413-22, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25676130

RESUMO

PURPOSE: To identify reversible risk factors for Clostridium difficile infection (CDI) after kidney transplantation (KT) that could lead to a reduction in its incidence and associated complications. METHODS: We performed a single-center case-control study in which 41 patients undergoing KT between February 2009 and July 2013 who developed a first episode of post-transplant CDI were included as cases. Patients transplanted at the same calendar day (± 2 weeks) as each case with no evidence of CDI and comparable risk exposure period were chosen as controls (2:1 ratio). Serum immunoglobulin and complement levels were systematically measured at baseline and months 1 and 6 after transplantation. RESULTS: Multivariate regression analysis identified age-adjusted Charlson comorbidity index (odds ratio [OR] per unitary increment 1.31; P value = 0.043), delayed graft function (OR 2.76; P value = 0.039), prior cytomegalovirus (CMV) disease (OR 6.85; P value = 0.011) and prior acute graft rejection (OR 5.92; P value = 0.008) as risk factors for post-transplant CDI. Cases with their first episode of CDI occurring beyond the first month were more likely to have IgG hypogammaglobulinemia (HGG) at month 1 (P value = 0.002), whereas cases with CDI beyond the sixth month were more likely to have HGG of any class at month 6 (P value = 0.003). Poor outcome (graft loss and/or all-cause mortality) was more common among cases (adjusted hazard ratio 5.69; P value = 0.001). CONCLUSION: The occurrence of CDI exerts a detrimental effect on graft and patient outcome. Post-transplant HGG was a potentially modifiable risk factor for CDI in KT recipients.


Assuntos
Agamaglobulinemia/complicações , Clostridioides difficile , Infecções por Clostridium/etiologia , Transplante de Rim , Complicações Pós-Operatórias , Adulto , Agamaglobulinemia/etiologia , Agamaglobulinemia/prevenção & controle , Idoso , Estudos de Casos e Controles , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/mortalidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taxa de Sobrevida
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