FABIANA AGENA
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
9 resultados
Resultados de Busca
Agora exibindo 1 - 9 de 9
- Seroconversion of 2009 pandemic influenza A (H1N1) vaccination in kidney transplant patients and the influence of different risk factors(2013) AZEVEDO, L. S.; GERHARD, J.; MIRAGLIA, J. L.; PRECIOSO, A. R.; TIMENETSKY, M. dC S. Tavares; AGENA, F.; GAMBA, C.; YASUDA, M. A. Shikanai; DAVID-NETO, E.; PIERROTTI, L.BackgroundInfluenza may present a high morbidity and mortality in solid organ transplanted patients (SOTP). Annual influenza virus vaccine is recommended for SOTP. However, low levels of seroconversion in SOTP have been reported. The aim of this study was to evaluate the immunogenicity of 2009 pandemic influenza A (H1N1) - A(H1N1)pdm09 - vaccine in kidney transplant patients and to analyze which features might affect seroconversion. MethodsThis study was conducted from March to August 2010 at the Renal Transplantation Unit of University of SAo Paulo, Brazil. A total of 85 renal transplant patients attending the outpatient unit received one 15-g intramuscular dose of A(H1N1)pdm09 influenza vaccine (reassortant vaccine virus A/California/7/2009 [NYMC X-179A]). Blood samples were collected immediately before and 21days after the vaccine was given. Antibody response was measured by the standard hemagglutination-inhibition (HI) assay. The primary immunogenicity endpoint for this study was seroconversion in previously seronegative patients (HI titers <1:40), and the secondary endpoint was the identification of features that could affect seroconversion in this population. ResultsFive (5.9%) patients presented HI titers prevaccination 1:40 and were excluded from further analysis. Seroconversion in previously negative patients occurred in 27 (34%) of 80 patients. Prevaccination HI titers geometrical mean was 5.8 and postvaccination 19.6 (ratio 3.4). Significant seroconversion rate factors were female gender, non-Caucasian ethnicity, and post-transplant time before vaccination. No impact was seen on seroconversion for age, donor type, tacrolimus and cyclosporine blood levels, renal function, or blood lymphocyte counts. Mycophenolate (MPA) showed a lower rate of seroconversion when compared with azathioprine. Tacrolimus and cyclosporine had similar seroconversion rates. Sirolimus use was associated with the highest rate of seroconversion, although these patient numbers were low. Immunosuppresssion containing MPA was considerably less effective in seroconversion than drug combinations with no MPA. Patients receiving sirolimus had more chance of seroconversion. HI titers geometric means pre/post vaccine were as follows: MPA (n=56): 5.8/12.8; tacrolimus (n=50): 5.9/16.2; cyclosporine (n=18): 5.4/24.2; azathioprine (n=19): 6.2/51.6; and sirolimus (n=6): 8/80. By univariate analysis, being female and non-White were variables associated with 3.3 times more chance of seroconversion than being male and White. In the multivariate analysis, the variables remaining in the model showed similar hazard ratios. ConclusionsIn this study, the monovalent A(H1N1)pdm09 influenza vaccine demonstrated low rates of seroconversion, particularly in patients on MPA, but with potentially higher response rates in patients on sirolimus.
- Cytomegalovirus prophylaxis in seropositive renal transplant recipients receiving thymoglobulin induction therapy: Outcome and risk factors for late CMV disease(2018) JR, Jose O. Reusing; FEITOSA, Emanoela B.; AGENA, Fabiana; PIERROTTI, Ligia C.; AZEVEDO, Luiz S. F.; KOTTON, Camille N.; DAVID-NETO, EliasBackgroundAnti-thymocyte globulin (ATG) therapy is a risk factor for cytomegalovirus (CMV) disease in renal transplant (RTx) recipients and therefore antiviral prophylaxis is commonly used. We evaluated the outcome of our current policy of 90days of CMV prophylaxis in seropositive recipients given ATG and the risk factors for the occurrence of CMV disease after prophylaxis. MethodsWe studied a retrospective cohort of 423 RTx (2010-2014) CMV-seropositive adults given ATG induction therapy. Results54 (13%) patients developed CMV disease at a median of 163days after transplant, of which 29 (54%) had viral syndrome and 25 (46%) had invasive disease. Median prophylaxis time (94days) and immunosuppressive drugs were similar between groups (CMV vs no-CMV). Those with CMV disease had more deceased donors and higher donor age, lower lymphocyte count, and lower median eGFR at day 90. Multivariable logistic regression analysis at day 90 and 180 found that eGFR 40ml/min/1.73m(2) (but not acute rejection) was associated with late CMV disease. In a separate validation cohort of 124 patients with 8% late CMV disease, eGFR 45 and lymphocyte count 800cells/mm(3) at the end of prophylaxis remained predictive of late CMV disease occurrence. ConclusionsThese data indicate that antiviral prophylaxis adequately prevented CMV in seropositive recipients given ATG, but late disease still occurred. Low eGFR and low lymphocyte count at the end of prophylaxis may help identify patients at higher risk of CMV disease.
- Recurrence of IgA Nephropathy after Kidney Transplantation in Adults(2021) UFFING, Audrey; PEREZ-SAEZ, Maria Jose; JOUVE, Thomas; BUGNAZET, Mathilde; MALVEZZI, Paolo; MUHSIN, Saif A.; LAFARGUE, Marie-Camille; REINDL-SCHWAIGHOFER, Roman; MORLOCK, Alina; OBERBAUER, Rainer; BUXEDA, Anna; BURBALLA, Carla; PASCUAL, Julio; MOOS, Seraina von; SEEGER, Harald; MANNA, Gaetano La; COMAI, Giorgia; BINI, Claudia; RUSSO, Luis Sanchez; FAROUK, Samira; NISSAISORAKARN, Pitchaphon; PATEL, Het; AGRAWAL, Nikhil; MASTROIANNI-KIRSZTAJN, Gianna; MANSUR, Juliana; TEDESCO-SILVA, Helio; VENTURA, Carlucci Gualberto; AGENA, Fabiana; DAVID-NETO, Elias; AKALIN, Enver; ALANI, Omar; MAZZALI, Marilda; MANFRO, Roberto Ceratti; BAUER, Andrea Carla; WANG, Aileen X.; CHENG, Xingxing S.; SCHOLD, Jesse D.; BERGER, Stefan P.; CRAVEDI, Paolo; RIELLA, Leonardo V.Background and objectives In patients with kidney failure due to IgA nephropathy, IgA deposits can recur in a subsequent kidney transplant. The incidence, effect, and risk factors of IgA nephropathy recurrence is unclear, because most studies have been single center and sample sizes are relatively small. Design, setting, participants, & measurements We performed a multicenter, international, retrospective study to determine the incidence, risk factors, and treatment response of recurrent IgA nephropathy after kidney transplantation. Data were collected from all consecutive patients with biopsy-proven IgA nephropathy transplanted between 2005 and 2015, across 16 ""The Post-Transplant Glomerular Disease"" study centers in Europe, North America, and South America. Results Out of 504 transplant recipients with IgA nephropathy, recurrent IgA deposits were identified by kidney biopsy in 82 patients; cumulative incidence of recurrence was 23% at 15 years (95% confidence interval, 14 to 34). Multivariable Cox regression revealed a higher risk for recurrence of IgA deposits in patients with a pre-emptive kidney transplant (hazard ratio, 3.45; 95% confidence interval, 1.31 to 9.17) and in patients with preformed donor-specific antibodies (hazardratio, 2.59; 95% confidence interval, 1.09 to 6.19). After kidney transplantation, development of de novo donor-specific antibodies was associated with subsequent higher risk of recurrence of IgA nephropathy (hazard ratio, 6.65; 95% confidence interval, 3.33 to 13.27). Immunosuppressive regimen was not associated with recurrent IgA nephropathy in multivariable analysis, including steroid use. Graft loss was higher in patients with recurrence of IgA nephropathy compared with patients without (hazard ratio, 3.69; 95% confidence interval, 2.04 to 6.66), resulting in 32% (95% confidence interval, 50 to 82) graft loss at 8 years after diagnosis of recurrence. Conclusions In our international cohort, cumulative risk of IgA nephropathy recurrence increased after transplant and was associated with a 3.7-fold greater risk of graft loss.
- Home blood pressure (BP) monitoring in kidney transplant recipients is more adequate to monitor BP than office BP(2011) AGENA, Fabiana; PRADO, Elisangela dos Santos; SOUZA, Patricia Soares; SILVA, Giovanio Vieira da; LEMOS, Francine Brambate Carvalhinho; MION JR., Decio; NAHAS, William Carlos; DAVID-NETO, EliasBackground. Hypertension is highly prevalent among kidney transplantation recipients and considered as an important cardiovascular risk factor influencing patient survival and kidney graft survival. Aim. Compare the blood pressure (BP) control in kidney transplant patients through the use of home blood pressure monitoring (HBPM) is more comparable with the results of ambulatory blood pressure monitoring compared to the measurement of office blood pressure. Methods. From March 2008 to April 2009 prospectively were evaluated 183 kidney transplant recipients with time after transplantation between 1 and 10 years. Patients underwent three methods for measuring BP: office blood pressure measurement (oBP), HBPM and ambulatory blood pressure monitoring (ABPM). Results. In total, 183 patients were evaluated, among them 94 were men (54%) and 89 women (46%). The average age was 50 6 11 years. The average time of transplant was 57 6 32 months. Ninety-nine patients received grafts from deceased donors (54%) and 84 were recipients of living donors (46%). When assessed using oBP, 56.3% presented with uncontrolled and 43.7% with adequate control of BP with an average of 138.9/82.3 +/- 17.8/12.1 mmHg. However, when measured by HBPM, 55.2% of subjects were controlled and 44.8% presented with uncontrolled BP with an average of 131.1/78.5 +/- 17.4/8.9 mmHg. Using the ABPM, we observed that 63.9% of subjects were controlled and 36.1% of patients presented uncontrolled BP with an average 128.8/80.5 +/- 12.5/8.1 mmHg. We found that the two methods (oBP and HBPM) have a significant agreement, but the HBPM has a higher agreement that oBP, confirmed P = 0.026. We found that there is no symmetry in the data for both methods with McNemar test. The correlation index of Pearson linear methods for the ABPM with the other two methods were 0.494 for office measurement and 0.768 for HBPM, best value of HBPM with ABPM. Comparing the errors of the two methods by paired t-test, we obtained the descriptive level of 0.837. Looking at the receiver operating characteristic curve for BP measurements in each method, we observed that oBP is lower than those obtained by HBPM in relation to ABPM. Conclusion. We conclude that the results obtained with HBPM were closer to the ABPM results than those obtained with BP obtained at oBP, being more sensitive to detect poor control of hypertension in renal transplant recipients.
- Discovery and cross-validation of peripheral blood and renal biopsy gene expression signatures from ethnically diverse kidney transplant populations(2019) VENTURA, Carlucci G.; WHISENANT, Thomas; GELBART, Terri; DAVID, Daisa S. R.; AGENA, Fabiana; SALOMON, Daniel R.; DAVID-NETO, Elias; KURIAN, Sunil M.We determined peripheral blood (PB) and biopsy (Bx) RNA expression signatures in a Brazilian and US cohort of kidney transplant patients. Phenotypes assigned by precise histology were: acute rejection (AR), interstitial fibrosis/tubular atrophy/chronic rejection (CR), excellent functioning transplants (TX), and glomerulonephritis recurrence (GN). Samples were analyzed on microarrays and profiles from each cohort were cross-validated on the other cohort with similar phenotypes. We discovered signatures for each tissue: (1) AR vs TX, (2) CR vs TX, and (3) GN vs TX using the Random Forests algorithm. We validated biopsies signatures of AR vs TX (area under the curve [AUC] 0.97) and CR vs TX (AUC 0.87). We also validated both PB and Bx signatures of AR vs TX and CR vs TX with varying degrees of accuracy. Several biological pathways were shared between AR and CR, suggesting similar rejection mechanisms in these 2 clinical phenotypes. Thus, we identified gene expression signatures for AR and CR in transplant patients and validated them in independent cohorts of significantly different racial/ethnic backgrounds. These results reveal that there are strong unifying immune mechanisms driving transplant diseases and identified in the signatures discovered in each cohort, suggesting that molecular diagnostics across populations are feasible despite ethnic and environmental differences.
- Recurrence of FSGS after Kidney Transplantation in Adults(2020) UFFING, Audrey; PEREZ-SAEZ, Maria Jose; MAZZALI, Marilda; MANFRO, Roberto C.; BAUER, Andrea Carla; DRUMOND, Frederico de Sottomaior; O'SHAUGHNESSY, Michelle M.; CHENG, Xingxing S.; CHIN, Kuo-Kai; VENTURA, Carlucci G.; AGENA, Fabiana; DAVID-NETO, Elias; MANSUR, Juliana B.; KIRSZTAJN, Gianna Mastroianni; JR, Helio Tedesco-Silva; V, Gilberto M. Neto; ARIAS-CABRALES, Carlos; BUXEDA, Anna; BUGNAZET, Mathilde; JOUVE, Thomas; MALVEZZI, Paolo; AKALIN, Enver; ALANI, Omar; AGRAWAL, Nikhil; MANNA, Gaetano La; COMAI, Giorgia; BINI, Claudia; MUHSIN, Saif A.; RIELLA, Miguel Carlos; HOKAZONO, Silvia R.; FAROUK, Samira S.; HAVERLY, Meredith; MOTHI, Suraj Sarvode; BERGER, Stefan P.; CRAVEDI, Paolo; V, Leonardo RiellaBackground and objectivesFSGS recurrence after kidney transplantation is a major risk factor for graft loss. However, the natural history, clinical predictors, and response to treatment remain unclear because of small sample sizes and poor generalizability of single-center studies, and disease misclassification in registry-based studies. We therefore aimed to determine the incidence, predictors, and treatment response of recurrent FSGS in a large cohort of kidney transplant recipients.Design, setting, participants, & measurementsThe Post-Transplant Glomerular Disease (TANGO) project is an observational, multicenter, international cohort study that aims to investigate glomerular disease recurrence post-transplantation. Transplant recipients were screened for the diagnosis of idiopathic FSGS between 2005 and 2015 and details were recorded about the transplant, clinical outcomes, treatments, and other risk factors.ResultsAmong 11,742 kidney transplant recipients screened for FSGS, 176 had a diagnosis of idiopathic FSGS and were included. FSGS recurred in 57 patients (32%; 95% confidence interval [95% CI], 25% to 39%) and 39% of them lost their graft over a median of 5 (interquartile range, 3.0?8.1) years. Multivariable Cox regression revealed a higher risk for recurrence with older age at native kidney disease onset (hazard ratio [HR], 1.37 per decade; 95% CI, 1.09 to 1.56). Other predictors were white race (HR, 2.14; 95% CI, 1.08 to 4.22), body mass index at transplant (HR, 0.89 per kg/m(2); 95% CI, 0.83 to 0.95), and native kidney nephrectomies (HR, 2.76; 95% CI, 1.16 to 6.57). Plasmapheresis and rituximab were the most frequent treatments (81%). Partial or complete remission occurred in 57% of patients and was associated with better graft survival.ConclusionsIdiopathic FSGS recurs post-transplant in one third of cases and is associated with a five-fold higher risk of graft loss. Response to treatment is associated with significantly better outcomes but is achieved in only half of the cases.
- Determination of viremia cut-off for risk to develop BKPyV-associated nephropathy among kidney transplant recipients(2018) BICALHO, Camila Silva; OLIVEIRA, Renato dos Reis; DAVID, Daisa Ribeiro; FINK, Maria Cristina Domingues Silva; AGENA, Fabiana; CASTRO, Maria Cristina; PANUTTI, Claudio; DAVID-NETO, Elias; PIERROTTI, Ligia CameraBackgroundBK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) is a consequence of BKPyV replication in the urinary tract in kidney transplant recipients (KTR). ObjectivesThe objectives were to determine the prevalence of BKPyV replication and BKPyVAN, risk factors associated to sustained viremia and BKPyVAN, and viremia cut-off that best predict the occurrence of sustained viremia and nephropathy in KTR of a single University Hospital Kidney Transplant Center. Patients and MethodsAll KTR undergoing transplantation from August 2010 to December 2011 were enrolled and monitored up to 2years posttransplantation for BKPyV viruria by decoy cells shedding or polymerase chain reaction (PCR) and viremia by PCR. Kidney biopsy was indicated if sustained viremia (two or more viremia above 10000copies/mL) to confirm BKPyVAN diagnosis. ResultsIn this study, 326 transplants were performed and 246 patients were included. Prevalence of viruria was 36.9%, viremia 22.3% and nephropathy 3.2%. Male gender was the only risk factor associated to sustained viremia or nephropathy. Cut-off value of viremia that best discriminates the progression to sustained viremia and to BKPyVAN was 37488 and 44956copies/mL, respectively. ConclusionsPrevalence of viruria, viremia, and nephropathy were similar to those reported in literature but the cut-off value of viremia that best discriminates the risk of progression to nephropathy was greater than the value usually reported, which is 10000copies/mL.
- Effect of polyoma viremia on 3-year allograft kidney function(2019) DAVID-NETO, Elias; AGENA, Fabiana; DAVID, Daisa Silva Ribeiro; PAULA, Flavio Jota de; PIERROTTI, Ligia Camera; FINK, Maria Cristina Domingues; AZEVEDO, Luiz Sergio Fonseca deBackground Polyoma viremia is associated with damage to renal tubular and urothelial cells. This may imply that a certain level of viremia, even cleared thereafter, could be associated with long-term renal dysfunction. Methods We, retrospectively, analyzed 390 first renal transplants adult recipients (>= 18 years) who were monitored for BK viremia in the first 12 months and evaluated estimated GFR (MDRD-4 equation) at 1 month and at the last follow-up (959 +/- 392 days). Results One hundred and ninety-nine patients (51%) developed at least one positive viremia: 105 (53%) low viremia (<10(4) copies/mL), 36 (18%) high viremia (4 x 10(4) > viremia >= 10(4) copies/mL) and 58 (15%) viremia (>= 4 x 10(4) copies/mL) consistent with polyoma virus associated nephropathy (PyVAN). Out of these 58 patients, 24 (6%) developed bx-proven (SV40+) PyVAN and 34(8.7%) presumptive PyVAN (SV40-). Baseline characteristics, immunosuppression, KDRI, rejection episodes, etc., did not differ among groups but there were more deceased donors and ATG induction therapy in the high viremia group. At last follow-up, all patients in the low, high viremia and presumptive PyVAN (except 2) had cleared BK viremia. Bx-proven PyVAN led to 14 graft losses, 10 due to PyVAN. In the presumptive PyVAN there was only one graft loss registered as due to PyVAN. eGFR, at 1 month after KTx, did not differ among groups (51 +/- 22 vs 48 +/- 24 vs 45 +/- 27 vs 43 +/- 18 vs 46 +/- 22 mL/min/1.73 m(2)), for no, low and high viremia as well for presumptive PyVAN and bx-proven PyVAN groups, respectively. At the last follow-up, eGFR did not differ between the no, low, and high viremia compared to baseline and to each other but was statistically lower in the presumptive and bx-proven PyVAN (38 +/- 15 and 17 +/- 7 mL/min/1.73 m(2)) either compared to baseline or to the other groups. Conclusions This study shows that low and high levels of BK viremia do not lead to GFR changes although very high viremia levels, compatible with presumptive or bx-proven PyVAN, even if cleared thereafter, lead to allograft damage and decreased GFR.
- The impact of mTOR inhibitors in the regression of left ventricular hypertrophy in elderly kidney transplant recipients(2022) DAVID-NETO, Elias; MENEZES FILHO, Marcelo Paes; SA, Italo Jose Araujo Silveira de; AGENA, Fabiana; ANDRADE, Jose Lazaro de; PAULA, Flavio Jota deEnd-stage kidney disease is frequently associated with left ventricular hypertrophy (LVH), a condition more prevalent in the elderly, that may increase mortality after renal transplantation (RTx). Previous studies suggested that mTOR inhibitors (mTORi) can improve LVH, but this has never been tested in elderly kidney transplant recipients. In this prospective randomized clinical trial, we analyzed the impact of Everolimus (EVL) on the reversal of LVH after RTx in elderly recipients (>= 60 years) submitted to different immunosuppressive regimens: EVL/lowTacrolimus (EVL group, n = 53) or mycophenolate sodium/regularTacrolimus (MPS group, n = 47). Patients performed echocardiograms (Echo) up to 3 months after RTx and then annually. At baseline, mean age was 65 +/- 3 years in both groups and LVH was observed in 63.6% of patients in EVL group and in 61.8% of MPS group. Last Echo was performed at mean time of 47 and 49 months after RTx in EVL and MPS groups, respectively (P = .34). LVH regression was observed in 23.8% (EVL group) and 19% (MPS group) of patients (P = 1.00). Mean eGFR, blood pressure, and use of RAS blockers were similar between groups throughout follow-up. EVL did not improve LVH in this cohort, and this lack of benefit may be attributed to concomitant use of TAC, senescence, or both.