FRANCINE BRAMBATE CARVALHINHO LEMOS
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
18 resultados
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Agora exibindo 1 - 10 de 18
- The impact of pretransplant donor-specific antibodies on graft outcome in renal transplantation: a six-year follow-up study(2012) DAVID-NETO, Elias; SOUZA, Patricia Soares; PANAJOTOPOULOS, Nicolas; RODRIGUES, Helcio; VENTURA, Carlucci Gualberto; DAVID, Daisa Silva Ribeiro; LEMOS, Francine Brambate Carvalhinho; AGENA, Fabiana; NAHAS, William Carlos; KALIL, Jorge Elias; CASTRO, Maria Cristina RibeiroOBJECTIVE: The significance of pretransplant, donor-specific antibodies on long-term patient outcomes is a subject of debate. This study evaluated the impact and the presence or absence of donor-specific antibodies after kidney transplantation on short-and long-term graft outcomes. METHODS: We analyzed the frequency and dynamics of pretransplant donor-specific antibodies following renal transplantation from a randomized trial that was conducted from 2002 to 2004 and correlated these findings with patient outcomes through 2009. Transplants were performed against a complement-dependent T-and B-negative crossmatch. Pre- and posttransplant sera were available from 94 of the 118 patients (80%). Antibodies were detected using a solid-phase (Luminex (R)), single-bead assay, and all tests were performed simultaneously. RESULTS: Sixteen patients exhibited pretransplant donor-specific antibodies, but only 3 of these patients (19%) developed antibody-mediated rejection and 2 of them experienced early graft losses. Excluding these 2 losses, 6 of 14 patients exhibited donor-specific antibodies at the final follow-up exam, whereas 8 of these patients (57%) exhibited complete clearance of the donor-specific antibodies. Five other patients developed ""de novo'' posttransplant donor-specific antibodies. Death-censored graft survival was similar in patients with pretransplant donor-specific and non-donor-specific antibodies after a mean follow-up period of 70 months. CONCLUSION: Pretransplant donor-specific antibodies with a negative complement-dependent cytotoxicity crossmatch are associated with a risk for the development of antibody-mediated rejection, although survival rates are similar when patients transpose the first months after receiving the graft. Our data also suggest that early posttransplant donor-specific antibody monitoring should increase knowledge of antibody dynamics and their impact on long-term graft outcome.
- Chikungunya in kidney transplant recipients: A series of cases(2017) PIERROTTI, Ligia Camera; LOPES, Max Igor Banks Ferreira; NASCIMENTO, Ana Patricia do; CAIAFFA-FILHO, Helio; LEMOS, Francine Brambate Carvalhinho; REUSING JR., Jose Otto; SEJAS, Odeli Nicole Encinas; DAVID-NETO, Elias; AZEVEDO, Luiz SergioChikungunya (CHIK) is a mosquito-borne virus (CHIKV) infection that recently appeared in the Americas and thousands of confirmed cases have been reported in Brazil since the first autochthonous cases were reported in September 2014. We reported four cases of CHIK in kidney transplant recipients. The diagnosis was confirmed by positive CHIKV real-time polymerase chain reaction in two cases and positive CHIKV-IgM serology in two patients. The time between transplantation and CHIKV infection ranged from 2 to 11 years. All of them had arthralgia, and 3 of them had fever. Other symptoms were mild conjunctivitis, rash, and retro-orbital pain. Kidney function remained stable in all cases. In three patients prednisone doses were temporally increased and the symptoms disappeared concurrently with the increase of the dose. As for the fourth patient, the prednisone dose remained unchanged and yet she improved. Other immunosuppressive drugs were not changed for the four cases. As far as we know, there are only two previously reported cases of CHIK among solid organ transplant recipients besides the four cases reported here. Despite the small number of cases, we can speculate that the use of immunosuppression might have played a role in the paucity of symptoms and the gradual complete recovery with no complication. (C) 2017 The Authors.
- Regulatory/inflammatory cellular response discrimination in operational tolerance(2019) CARMONA, Priscila; MEDINA-ARMENTEROS, Yordanka; CABRAL, Amanda; MONTEIRO, Sandra Maria; FONSECA, Simone Goncalves; FARIA, Ana Caetano; LEMOS, Francine; SAITOVITCH, David; NORONHA, Irene L.; KALIL, Jorge; COELHO, VeronicaBackground. Antigen-specific cellular response is essential in immune tolerance. We tested whether antigen-specific cellular response is differentially modulated in operational tolerance (OT) in renal transplantation with respect to critical antigenic challenges in allotransplantation-donor antigens, pathogenic antigens and self-antigens. Methods. We analysed the profile of immunoregulatory (REG) and pro-inflammatory (INFLAMMA) cytokines for the antigen-specific response directed to these three antigen groups, by Luminex. Results. We showed that, in contrast to chronic rejection and healthy individuals, OT gives rise to an immunoregulatory deviation in the cellular response to donor human leucocyte antigen DR isotype peptides, while preserving the pro-inflammatory response to pathogenic peptides. Cellular autoreactivity to the N6 heat shock protein 60 (Hsp60) peptide also showed a REG profile in OT, increasing IL4, IL-5, IL-10 and IL-13. Conclusions. The REG shift of donor indirect alloreactivity in OT, with inhibition of interleukin (IL)-1B, IL-8, IL-12, IL-17, granulocyte colony-stimulating factor, Interferon-gamma and monocyte chemoattractant protein-1, indicates that this may be an important mechanism in OT. In addition, the differential REG profile of cellular response to the Hsp60 peptide in OT suggests that REG autoimmunity may also play a role in human transplantation tolerance. Despite cross-reactivity of antigen-specific T cell responses, a systemic functional antigen-specific discrimination takes place in OT.
- Preserving the B-Cell Compartment Favors Operational Tolerance in Human Renal Transplantation(2012) SILVA, Hernandez M.; TAKENAKA, Maisa C. S.; MORAES-VIEIRA, Pedro M. M.; MONTEIRO, Sandra M.; HERNANDEZ, Maristela O.; CHAARA, Wahiba; SIX, Adrien; AGENA, Fabiana; SESTERHEIM, Patricia; BARBE-TUANA, Florencia Maria; SAITOVITCH, David; LEMOS, Francine; KALIL, Jorge; COELHO, VeronicaTransplanted individuals in operational tolerance (OT) maintain long-term stable graft function after completely stopping immunosuppression. Understanding the mechanisms involved in OT can provide valuable information about pathways to human transplantation tolerance. Here we report that operationally tolerant individuals display quantitative and functional preservation of the B-c ell compartment in renal transplantation. OT exhibited normal numbers of circulating total B cells, naive, memory and regulatory B cells (Bregs) as well as preserved B-cell receptor repertoire, similar to healthy individuals. In addition, OT also displayed conserved capacity to activate the cluster of differentiation 40 (CD40)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in Bregs, in contrast, with chronic rejection. Rather than expansion or higher activation, we show that the preservation of the B-cell compartment favors OT. Online address: http://www.molmed.org doi: 10.2119/molmed.2011.00281
- Alteracoes vasculares em rins de doadores falecidos retardam a recuperacao da funcao do enxerto apos o transplante renal(2014) MARQUES, Igor Denizarde Bacelar; REPIZO, Liliany Pinhel; PONTELLI, Renato; PAULA, Flavio Jota de; NAHAS, William Carlos; DAVID, Daisa Silva Ribeiro; DAVID NETO, Elias; LEMOS, Francine Brambate CarvalhinhoObjective: The purpose of this study was to evaluate the impact of donor and recipient characteristics on duration of delayed graft function (DGF) and 1-year serum creatinine (SCr), as a surrogate endpoint for allograft survival. Methods: We reviewed 120 first cadaver kidney transplants carried out consecutively at our center to examine the effect on 1-year SCr of the presence and duration of DGF. Results: DGF rate was 68%, with a median duration of 12 days (range, 1-61). Forty-four (38%) patients presented DGF lasting 12 or more days (prolonged DGF group). Mean donor age was 43 ± 13 years, 37% had hypertension and in 59% the cause of brain death was cardiovascular accident. The mean cold ischemia time was 23 ± 5 hours. Twenty-seven (23%) donors were classified as expanded-criteria donors according to OPTN criteria. The mean recipient age was 51 ± 15 years. The recipients median time in dialysis was 43 months (range, 1-269) and 25% of them had panel reactive antibodies > 0%. Patients with prolonged DGF presented higher 1-year SCr in comparison with patients without DGF (1.7 vs. 1.3 mg/dL, respectively, p = 0.03). In multivariate logistic regression analysis, the only significant factor contributing to the occurrence of prolonged DGF was the presence of vascular lesions in the kidney allograft at time of transplantation (HR 3.6, 95% CI 1.2-10.2; p = 0.02). Conclusion: The presence of vasculopathy in the kidney allograft at time of transplantation was identified as an important factor independently associated with prolonged DGF. Prolonged DGF negatively impacts 1-year graft function.
- Aging and End Stage Renal Disease Cause A Decrease in Absolute Circulating Lymphocyte Counts with A Shift to A Memory Profile and Diverge in Treg Population(2019) FREITAS, Geraldo Rubens Ramos; FERNANDES, Maria da Luz; AGENA, Fabiana; JALUUL, Omar; SILVA, Sergio Colenci; LEMOS, Francine Brambate Carvalhinho; COELHO, Veronica; DAVID-NETO, Elias; GALANTE, Nelson ZocolerThere is a growing number of elderly kidney transplant (Ktx) recipients. Elderly recipients present lower acute rejection rates but higher incidence of infection and malignancies. Aging per se seems to result in a shift to memory profile and chronic kidney disease (CKD) in premature immunological aging. Understanding aging and CKD effects on the immune system can improve elderly Ktx immunosuppression. We analyzed the effects of aging and CKD in the immune system, comparing healthy adults (HAd) (n=14, 26 +/- 2y), healthy elderly (HEld) (n=15, 79 +/- 7y), end stage renal disease (ESRD) adults (EnAd) (n=18, 36 +/- 7y) and ESRD elderly (EnEld) (n=31, 65 +/- 3y) prior to Ktx regarding their naive, memory and regulatory T and B peripheral lymphocytes. Aging and ESRD presented additive effect decreasing absolute numbers of B and T-lymphocytes, affecting memory, naive and regulatory subsets without synergic effect. Both resulted in higher percentages of T memory subsets and opposing effects on regulatory T (TREG) subsets, higher percentage in aging and lower in ESRD. Combined effect of aging and ESRD also resulted in higher regulatory B cell percentages. In addition to global lymphopenia and TCD4(+) memory shift in both aging and ESRD, aging shifts to an immunoregulatory profile, inducing a increase in TREG percentages, contrasting with ESRD that decreases TREGs. Differential immunosuppression regimens for elderly Ktx may be required.
- 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.
- Differential microRNA Profile in Operational Tolerance: A Potential Role in Favoring Cell Survival(2019) CABRAL, Amanda; CANDIDO, Daran da Silva; MONTEIRO, Sandra Maria; LEMOS, Francine; SAITOVITCH, David; NORONHA, Irene L.; ALVES, Leticia Ferreira; GERAIDO, Murilo Vieira; KALIL, Jorge; CUNHA-NETO, Edecio; FERREIRA, Ludmila Rodrigues Pinto; COEIHO, VeronicaBackground: Operational tolerance (OT) is a state of graft functional stability that occurs after at least 1 year of immunosuppressant withdrawal. MicroRNAs (microRNA) are small non-coding RNAs that downregulate messenger RNA/protein expression of innumerous molecules and are critical for homeostasis. We investigated whether OT in kidney transplantation displays a differential microRNA profile, which would suggest that microRNAs participate in Operational Tolerance mechanisms, and may reveal potential molecular pathways. Methods: We first compared serum microRNA in OT (n = 8) with chronic rejection (CR) (n = 5) and healthy individuals (HI) (n = 5), using a 768-microRNA qPCR-panel. We used the Thermo Fisher Cloud computing platform to compare the levels of microRNAs in the OT group in relation to the other study groups. We performed validation experiments for miR-885-5p, by q-PCR, in a larger number of study subjects (OT = 8, CR = 12, HI = 12), as individual samples. Results: We detected a differential microRNA profile in OT vs. its opposing clinical outcome-CR-suggesting that microRNAs may integrate transplantation tolerance mechanisms. Some miRNAs were detected at higher levels in OT: miR-885-5p, miR-331-3p, miR-27a-5p vs. CR; others, we found at lower levels: miR-1233-3p, miR-572, miR-638, miR-1260a. Considering highly predicted/experimentally demonstrated targets of these miRNAs, bioinformatics analysis revealed that the granzyme B, and death receptor pathways are dominant, suggesting that cell death regulation integrates transplantation tolerance mechanisms. We confirmed higher miR-885-5p levels in OT vs. CR, and vs. HI, in a larger number of subjects. Conclusions: We propose that epigenetics mechanisms involving microRNAs may integrate human transplantation tolerance mechanisms, and regulate key members of the cell death/survival signaling. miR-885-5p could favor cell survival in OT by diminishing the levels of CRADD/RAIDD and CASP3. Nonetheless, given the nature of any complex phenomenon in humans, only cumulative data will help to determine whether this microRNA differential profile may be related to the cause or consequence of operational tolerance.
- Randomized Trial of Machine Perfusion Versus Cold Storage in Recipients of Deceased Donor Kidney Transplants With High Incidence of Delayed Graft Function(2017) TEDESCO-SILVA JUNIOR, Helio; OFFERNI, Juliano Chrystian Mello; CARNEIRO, Vanessa Ayres; PAULA, Mayara Ivani de; NETO, Elias David; LEMOS, Francine Brambate Carvalhinho; MOURA, Lucio Roberto Requiao; SILVA FILHO, Alvaro Pacheco e; CUNHA, Mirian de Fatima de Morais; SILVA, Erica Francisco da; MIORIN, Luiz Antonio; DEMETRIO, Daniela Priscila; LUCONI, Paulo Sergio; LUCONI, Waldere Tania da Silva; BOBBIO, Savina Adriana; KUSCHNAROFF, Liz Milstein; NORONHA, Irene Lourdes; BRAGA, Sibele Lessa; BARSANTE, Renata Cristina; MOREIRA, Joao Cezar Mendes; FERNANDES-CHARPIOT, Ida Maria Maximina; ABBUD-FILHO, Mario; ANDRADE, Luis Gustavo Modelli de; GARCIA, Paula Dalsoglio; SABER, Luciana Tanajura Santamaria; LAURINDO, Alan Fernandes; CHOCAIR, Pedro Renato; CUVELLO NETO, Americo Lourenco; ZANOCCO, Juliana Aparecida; SOARES FILHO, Antonio Jose Duboc de Almeida; AGUIAR, Wilson Ferreira; PESTANA, Jose MedinaBackground. This study compared the use of static cold storage versus continuous hypothermic machine perfusion in a cohort of kidney transplant recipients at high risk for delayed graft function (DGF). Methods. In this national, multicenter, and controlled trial, 80 pairs of kidneys recovered from brain-dead deceased donors were randomized to cold storage or machine perfusion, transplanted, and followed up for 12 months. The primary endpoint was the incidence of DGF. Secondary endpoints included the duration of DGF, hospital stay, primary nonfunction, estimated glomerular filtration rate, acute rejection, and allograft and patient survivals. Results. Mean cold ischemia time was high but not different between the 2 groups (25.6 +/- 6.6 hours vs 25.05 +/- 6.3 hours, 0.937). The incidence of DGF was lower in the machine perfusion compared with cold storage group (61% vs. 45%, P = 0.031). Machine perfusion was independently associated with a reduced risk of DGF (odds ratio, 0.49; 95% confidence interval, 0.26-0.95). Mean estimated glomerular filtration rate tended to be higher at day 28 (40.6 +/- 19.9 mL/min per 1.73 m(2) vs 49.0 +/- 26.9 mL/min per 1.73 m(2); P = 0.262) and 1 year (48.3 +/- 19.8 mL/min per 1.73 m2 vs 54.4 +/- 28.6 mL/min per 1.73 m(2); P = 0.201) in the machine perfusion group. No differences in the incidence of acute rejection, primary nonfunction (0% vs 2.5%), graft loss (7.5% vs 10%), or death (8.8% vs 6.3%) were observed. Conclusions. In this cohort of recipients of deceased donor kidneys with high mean cold ischemia time and high incidence of DGF, the use of continuous machine perfusion was associated with a reduced risk of DGF compared with the traditional cold storage preservation method.
- Protective response in renal transplantation: no clinical or molecular differences between open and laparoscopic donor nephrectomy(2013) MACHADO, Christiano; MALHEIROS, Denise Maria Avancini Costa; ADAMY, Ari; SANTOS, Luiz Sergio; SILVA FILHO, Agenor Ferreira da; NAHAS, William Carlos; LEMOS, Francine Brambate CarvalhinhoOBJECTIVE: Prolonged warm ischemia time and increased intra-abdominal pressure caused by pneumoperitoneum during a laparoscopic donor nephrectomy could enhance renal ischemia reperfusion injury. For this reason, laparoscopic donor nephrectomy may be associated with a slower graft function recovery. However, an adequate protective response may balance the ischemia reperfusion damage. This study investigated whether laparoscopic donor nephrectomy modified the protective response of renal tissue during kidney transplantation. METHODS: Patients undergoing live renal transplantation were prospectively analyzed and divided into two groups based on the donor nephrectomy approach used: 1) the control group, recipients of open donor nephrectomy (n = 29), and 2) the study group, recipients of laparoscopic donor nephrectomy (n = 26). Graft biopsies were obtained at two time points: T-1 = after warm ischemia time and T+1 = 45 minutes after kidney reperfusion. The samples were analyzed by immunohistochemistry for the Bcl-2 and HO-1 proteins and by real-time polymerase chain reaction for the mRNA expression of Bcl-2, HO-1 and vascular endothelial growth factor. RESULTS: The area under the curve for creatinine and delayed graft function were similar in both the laparoscopic and open groups. There was no difference in the protective gene expression between the laparoscopic donor nephrectomy and open donor nephrectomy groups. The protein expression of HO-1 and Bcl-2 were similar between the open and laparoscopic groups. Furthermore, the gene expression of B-cell lymphoma 2 correlated with the warm ischemia time in the open group (p = 0.047) and that of vascular endothelial growth factor with the area under the curve for creatinine in the laparoscopic group (p = 0.01). CONCLUSION: The postoperative renal function and protective factor expression were similar between laparoscopic donor nephrectomy and open donor nephrectomy. These findings ensure laparoscopic donor nephrectomy utilization in renal transplantation.