FABIANA AGENA

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Lattes
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Instituto Central, Hospital das Clínicas, Faculdade de Medicina

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Assunto: renal-transplantation ×

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  • article 13 Citação(ões) na Scopus
    UPLC-MS/MS assay validation for tacrolimus quantitative determination in peripheral blood T CD4+and B CD19+lymphocytes
    (2018) ROMANO, Paschoalina; FERNANDES, Maria da Luz; EBNER, Persio de Almeida Rezende; OLIVEIRA, Nayara Duarte de; OKUDA, Larissa Mitsue; AGENA, Fabiana; MENDES, Maria Elizabete; SUMITA, Nairo Massakazu; COELHO, Veronica; DAVID-NETO, Elias; GALANTE, Nelson Zocoler
    Monitoring tacrolimus (Tac) exposure in cell matrices enriched with lymphocytes can improve Tac therapeutic drug monitoring (TDM) in solid organ transplant recipients. An UPLC-MS/MS based assay for Tac quantification in peripheral blood T CD4+ and B CD19+ lymphocytes was developed. Peripheral blood mononuclear cells (PBMC) were obtained by density gradient centrifugation and highly purified (purity >90%) T CD4+ and B CD19+ cell suspensions were acquired by magnetic negative selection from whole blood of 6 healthy volunteers. The purity of lymphocyte suspensions was checked by flow cytometry. Tac extraction was performed in a liquid-liquid zinc sulfate, methanol and acetonitrile based medium. Ascomycin was used as internal standard. The equipment used was a Waters (R) Acquity (TM) UPLC system (Waters Corporation, Milford, MA, USA). The chromatographic run was performed on a Waters (R) MassTrak TDM C18 (2.1 x 10 mm) column (Waters Corporation, Milford, MA, USA). at a flow rate of 0.4 mL/min. The instrument was set in electrospray positive ionization mode. The method was validated according to Clinical Laboratory Standard Institute (CLSI) guidelines and showed a high sensitivity and specificity over a range of 0-5.2 ng/mL in PBMC, 0-5.0 ng/mL in T CD4+ Lymphocytes and 0-5.3 ng/mL in B CD19+ lymphocytes. Precision was appropriate with CV of intra-assay quantifications ranging from 4.9 to 7.4%, and of inter-assay quantifications from 7.2 to 13.9%. Limit of detection and quantification were 0.100 and 0.115 ng/mL in PBMC, 0.058 and 0.109 ng/mL in T CD4+ and 0.017 and 0.150 ng/mL in B CD19+ cells. Matrix effect was not significant among all the studied matrices. Samples showed stability for Tac quantification over a period of 90 days either at room temperature or at -30 degrees C storage conditions. The method was applied to clinical samples of 20 kidney transplant recipients. Concentrations ranged from 2.200 to 11.900 ng/mL in whole blood, from 0.005 to 0.570 ng/10(6) cells in PBMC, from 0.081 to 1.432 ng/10(6) cells in T CD4+, and from 0.197 to 1.564 ng/10(6) cells in B CD19+ cell matrices. The method has potential applicability for Tac TDM in solid organ transplant recipients.
  • article 17 Citação(ões) na Scopus
    Diminished Mycophenolic Acid Exposure Caused by Omeprazole May Be Clinically Relevant in the First Week Posttransplantation
    (2012) DAVID-NETO, Elias; TAKAKI, Kelly M.; AGENA, Fabiana; ROMANO, Paschoalina; SUMITA, Nairo M.; MENDES, Maria E.; NERI, Leticia Aparecida Lopes; NAHAS, William C.
    Background: Some studies have reported a decreased absorption of mycophenolic acid (MPA) from mycophenolate mofetil (MMF) in renal transplanted (RTx) patients under proton-pump inhibitors (PPIs). There is still a lack of information regarding (1) whether this effect occurs when MMF is administered with either tacrolimus or cyclosporine A [calcineurin inhibitors (CNIs)], (2) whether the effect has the same amplitude during the first year after RTx, and finally (3) whether this decrease in exposure is clinically relevant. Methods: We retrospectively analyzed the omeprazole effect in 348 12-hour pharmacokinetic samplings [area under the curve (AUC) 0-12h] performed on days 7, 14, 30, 60, 180, and 360 after RTx in 77 patients who participated in previous trials. Results: For all periods, the groups with and without PPI did not differ in all variables. By mixed-model analysis of variance, PPI reduced the MPA AUC(0-12h) (P < 0.0008) in the patients under both CNIs mainly due to decreased absorption (P = 0.049). In the tacrolimus group, a lower exposure seemed also due to a decreased MPA reabsorption at 10-12 hours. The PPI effect remains throughout the first year but was clinically more important on day 7. By Cox analysis, the use of PPI was associated with a 25% less chance of being adequately exposed to MPA (95% confidence interval 0.58-0.99, P = 0.04). Similarly, the number of patients underexposed to MPA (AUC < 30 ng.h/mL) was higher at most periods in the PPI group but again not statistically significant. Conclusions: These data indicate that PPI decreases the MPA exposure when associated with both CNIs but particularly in the first week after RTx. In this period, the MMF dose should be increased. This effect lasts throughout the first year but does not seem to be clinically relevant after the first week.
  • article 88 Citação(ões) na Scopus
    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 Riella
    Background 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.
  • article 13 Citação(ões) na Scopus
    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 Camera
    BackgroundBK 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.
  • article 15 Citação(ões) na Scopus
    Exploring the causes of the high incidence of delayed graft function after kidney transplantation in Brazil: a multicenter study
    (2021) SANDES-FREITAS, Taina Veras de; MAZZALI, Marilda; MANFRO, Roberto Ceratti; ANDRADE, Luis Gustavo Modelli de; VICARI, Alessandra Rosa; SOUSA, Marcos Vinicius de; PESTANA, Jose Osmar Medina; GARCIA, Valter Duro; CARVALHO, Deise Rosa de Boni Monteiro de; ESMERALDO, Ronaldo de Matos; OLIVEIRA, Claudia Maria Costa de; SIMAO, Denise Rodrigues; DEBONI, Luciane Monica; DAVID-NETO, Elias; CAVALCANTI, Frederico Castelo Branco; PACHECO-SILVA, Alvaro; FERREIRA, Gustavo Fernandes; MADEIRA, Rafael Lage; BIGNELLI, Alexandre Tortoza; MEIRA, Geraldo Sergio Goncalves; LASMAR, Euler Pace; KEITEL, Elizete; MATUCK, Tereza de Azevedo; COSTA, Silvana Daher da; NGA, Hong Si; FERNANDES, Paula Frassinetti Castelo Branco Camurca; NARCISO, Humberto Rebello; VIEIRA, Marcos Alexandre; AGENA, Fabiana; FONSECA, Ivailda Barbosa; MATOS, Ana Cristina Carvalho de; BASTOS, Juliana; VILLACA, Sandra Simone; HOKAZONO, Silvia Regina; SILVA, Alberto Rafael Baleeiro; LASMAR, Marcus; TEDESCO-SILVA, Helio
    This retrospective multicenter (n = 18) cohort study evaluated the incidence, risk factors, and the impact of delayed graft function (DGF) on 1-year kidney transplant (KT) outcomes. Of 3992 deceased donor KT performed in 2014-2015, the incidence of DGF was 54%, ranging from 29.9% to 87.7% among centers. Risk factors ((lower-bound-95%CI) OR (upper-bound-95%CI)) were male gender ((1.066)1.249(1.463)), diabetic kidney disease ((1.053)1.296(1.595)), time on dialysis ((1.005)1.007(1.009)), retransplantation ((1.035)1.397(1.885)), preformed anti-HLA antibodies ((1.011)1.383(1.892)), HLA mismatches ((1.006)1.066(1.130)), donor age ((1.011)1.017(1.023)), donor final serum creatinine (sCr) ((1.239)1.317(1.399)), cold ischemia time (CIT) ((1.031)1.043(1.056)), machine perfusion ((0.401)0.542(0.733)), and induction therapy with rabbit antithymocyte globulin (rATG) ((0.658)0.800(0.973)). Duration of DGF > 4 days was associated with inferior renal function and DGF > 14 days with the higher incidences of acute rejection, graft loss, and death. In conclusion, the incidence and duration of DGF were high and associated with inferior graft outcomes. While late referral and poor donor maintenance account for the high overall incidence of DGF, variability in donor and recipient selection, organ preservation method, and type of induction agent may account for the wide variation observed among transplant centers.
  • article 2 Citação(ões) na Scopus
    Desensitization using IVIG alone for living-donor kidney transplant: impact on donor-specific antibodies
    (2022) ULISSES, Luiz Roberto de Sousa; PAIXAO, Jenaine Oliveira; AGENA, Fabiana; SOUZA, Patricia Soares de; PAULA, Flavio J.; BEZERRA, Gislene; RODRIGUES, Helcio; PANAJOTOPOLOUS, Nicolas; DAVID-NETO, Elias; CASTRO, Maria Cristina Ribeiro de
    Introduction: Sensitization to human leukocyte antigen is a barrier to. Few data have been published on desensitization using polyvalent human intravenous immunoglobulin (IVIG) alone. Methods: We retrospectively reviewed the of 45 patients with a positive complement-dependent cytotoxicity crossmatch (CDCXM) or flow cytometry crossmatch (FCXM) against living donors from January 2003 to December 2014. Of these, 12 were excluded. Patients received monthly IVIG infusions (2 g/kg) only until they had a negative T-cell and B-cell FCXM. Results: During the 33 patients, 22 (66.7%) underwent living donor kidney transplantation, 7 (21.2%) received a deceased donor graft, and 4 (12.1%) did not undergo transplantation. The median class I and II panel reactive antibodies for these patients were 80.5% (range 61%-95%) and 83.0% (range 42%-94%), respectively. Patients (81.8%) had a positive T-cell and/or B-cell CDCXM and 4 (18.2%) had a positive T-cell and/ or B-cell FCXM. Patients underwent transplantation after a median of 6 (range 3-16). The median donor-specific antibody mean fluorescence intensity sum was 5057 (range 2246-11,691) before and 1389 (range 934-2492) after desensitization (p = 0.0001). Mean patient follow-up time after transplantation was 60.5 (SD, 36.8) months. Nine patients (45.0%). Death-censored graft survival at 1, 3, and 5 years after transplant was 86.4, 86.4, and 79.2%, respectively and patient survival was 95.5, 95.5, and 83.7%, respectively. Conclusions: Desensitization using IVIG alone is an effective strategy, allowing successful transplantation in 87.9% of these highly sensitized patients.
  • article 4 Citação(ões) na Scopus
    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 de
    Background 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.
  • article 0 Citação(ões) na Scopus
    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 de
    End-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.
  • article
    The Kinetics of Anti-HLA Antibodies in the First Year after Kidney Transplantation: In Whom and When Should They Be Monitored?
    (2018) CASTRO, Maria Cristina Ribeiro de; BARBOSA, Erick A.; SOUZA, Renata P.; AGENA, Fabiana; SOUZA, Patricia S. de; MACIEL, Gabriella; RODRIGUES, Helcio; PANAJOTOPOULOS, Nicolas; DAVID, Daisa S.; PAULA, Flavio J. de; DAVID-NETO, Elias
    The impact of the kinetics of the anti-HLA antibodies after KTx on the occurrence of acute rejection as well as the better time-point to monitor anti-HLA Abs after transplantation is not completely defined. This prospective study followed 150 patients over 12 months after transplantation. Serum IgG anti-HLA Abs were detected by single antigen beads after typing donors and recipients for loci A, B, C, DR, and DQ. Before KTx, 89 patients did not present anti-HLA Abs and 2% developed ""de novo"" Abs during the 1st year, 39 patients were sensitized without DSAs, and 13% developed DSA after surgery; all of them presented ABMR. Sensitized patients presented higher acute rejection rates (36.4% versus 13.5%, P < 0.001), although 60% of the patients did not present ABMR. Patients, in whom DSA-MFI decreased during the first two weeks after surgery, did not develop ABMR. Those who sustained their levels presented a rate of 22% of ABMR. 85% of patients developed ABMR when MFIs increased early after transplantation (which occurred in 30% of the DSA positive patients). In the ABMR group, we observed an iDSA-MFI sharp drop on the fourth day and then an increase between the 7th and 14th POD, which suggests DSA should be monitored at this moment in sensitized patients for better ABMR prediction.