DAISA SILVA RIBEIRO DAVID
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina
33 resultados
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- 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.
- Banff 2013 Meeting Report: Inclusion of C4d-Negative Antibody-Mediated Rejection and Antibody-Associated Arterial Lesions(2014) HAAS, M.; SIS, B.; RACUSEN, L. C.; SOLEZ, K.; GLOTZ, D.; COLVIN, R. B.; CASTRO, M. C. R.; DAVID, D. S. R.; DAVID-NETO, E.; BAGNASCO, S. M.; CENDALES, L. C.; CORNELL, L. D.; DEMETRIS, A. J.; DRACHENBERG, C. B.; FARVER, C. F.; III, A. B. Farris; GIBSON, I. W.; KRAUS, E.; LIAPIS, H.; LOUPY, A.; NICKELEIT, V.; RANDHAWA, P.; RODRIGUEZ, E. R.; RUSH, D.; SMITH, R. N.; TAN, C. D.; WALLACE, W. D.; MENGEL, M.The 12th Banff Conference on Allograft Pathology was held in Comandatuba, Brazil, from August 19-23, 2013, and was preceded by a 2-day Latin American Symposium on Transplant Immunobiology and Immunopathology. The meeting was highlighted by the presentation of the findings of several working groups formed at the 2009 and 2011 Banff meetings to: (1) establish consensus criteria for diagnosing antibody-mediated rejection (ABMR) in the presence and absence of detectable C4d deposition; (2) develop consensus definitions and thresholds for glomerulitis (g score) and chronic glomerulopathy (cg score), associated with improved inter-observer agreement and correlation with clinical, molecular and serological data; (3) determine whether isolated lesions of intimal arteritis (isolated v) represent acute rejection similar to intimal arteritis in the presence of tubulointerstitial inflammation; (4) compare different methodologies for evaluating interstitial fibrosis and for performing/evaluating implantation biopsies of renal allografts with regard to reproducibility and prediction of subsequent graft function; and (5) define clinically and prognostically significant morphologic criteria for subclassifying polyoma virus nephropathy. The key outcome of the 2013 conference is defining criteria for diagnosis of C4d-negative ABMR and respective modification of the Banff classification. In addition, three new Banff Working Groups were initiated.
conferenceObject Plasma Cell Infiltration: General Overview of Clinical and Pathological Correlations in Renal Transplantation(2015) NIHEI, C.; LEMOS, F.; DAVID, D.; SOUZA, P.; PAULA, F. de; NAHAS, W.; DAVID-NETO, E.- 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.
- Expression patterns of CD56+and CD16+cells in renal transplant biopsies with acute rejection: Associations with microcirculation injuries and graft survival(2017) SANTOS, Daniela Cristina Dos; CAMARA, Niels Olsen Saraiva; DAVID, Daisa Silva Ribeiro; MALHEIROS, Denise Maria Avancini CostaBackgroundThe study investigated whether immunohistochemical features of interstitial and glomerular CD56 and CD16 infiltrates - NK cells markers - could be associated with microcirculation injury scores - peritubular capillaritis (ptc) and glomerulitis (g) - and graft survival. MethodsThe research analyzed the immunohistochemical pattern of CD56 and CD16 in interstitial and glomerular compartments of biopsies for-cause biopsies from 59 recipients diagnosed with acute rejection (mean=135.5days post-transplant). ResultsInterstitial CD56+ cells had an increased expression for glomerulitis (g1) (P=0.02) and peritubular capillaritis (ptc2) (P=0.003) presence. It was noted that interstitial CD56+cells with mean above 0.56cells/mm(2) had worse allograft survival. CD56+ cells in the interstitial compartment with mean less than or equal to 0.56cells/mm(2) was related with absence or mild peritubular capillaritis (P=0.012) and mean above 0.56cells/mm(2), respectively, with glomerulitis (P=0.002) presence. Interstitial CD16 cells showed greater positive results in relation to peritubular capillaritis (P=0.0001) cases. Similarly, it was observed that glomerular CD16+ cells had higher positive results in glomerulitis (P=0.009) presence. ConclusionsThe study findings showed that CD56+ cell infiltrated in the interstitial compartment was significantly associated with microcirculation injury scores, especially the glomerulitis, and graft survival. Summary at a Glance This study suggests that increased expression of interstitial natural killer cells in renal allograft biopsies of kidney transplant recipients with rejection may be associated with poorer graft outcomes.
- Non-Human Leukocyte Antigen Antibodies Reactive with Endothelial Cells Could Be Involved in Early Loss of Renal Allografts(2011) RONDA, C.; BORBA, S. C. P.; FERREIRA, S. C. P.; GLOTZ, D.; IANHEZ, L. E.; RODRIGUES, H.; VIGGIANI, C. S.; NAHAS, W.; DAVID-NETO, E.; CASTRO, M. C. R.; DAISA, S. R. David; KALIL, J.; PANAJOTOPOULOS, N.Preformed donor-specific human leukocyte antigen (HLA) antibodies have been associated with allograft dysfunction and failure. However, recipients of HLA-identical kidneys can develop acute humoral rejection, implicating putative pathogenic antibodies that are directed against non-HLA antigens. We investigated the presence of endothelial cell reactive antibodies in 11 patients who experienced early loss of their transplanted kidneys owing to humoral rejection and 1 loss from renal venal thrombosis. We examined the potential efficacy of intravenous immunoglobulin to block the binding of these antibodies, as previously suggested for anti-HLA antibodies.
conferenceObject Early Protocol Biopsies Can Identify Antibody-Mediated Rejection in Sensitized Patients(2013) SOUZA, P.; MACHADO, D.; AGUIRRE, A.; DAVID, D.; BARBOSA, E.; PAULA, F. de; NAHAS, W.; DAVID-NETO, E.; CASTRO, M.HLA sensitized patients are at risk for antibody-mediated rejection (ABMR). Our purpose was to evaluate the importance of early protocol biopsies. From Jul/2010 to Jun/2012, 101 sensitized patients defined as PRA>10% (class I and/or II by Flow-PRA) were transplanted at our institution. Out of them, 60 performed donor-specific antibodies (DSA) at transplant and a protocol-bx at day 7 (D7) and were included in this study. A second for cause indication biopsy (IB) was done at the physician’s discretion in 18 patients without previous acute rejection (AR) diagnosis. DSA were analyzed by single antigen bead assays at the time of biopsies (classified according to Banff’09 criteria). Patients (pts) mean age was 48±12 years, 48 were female (80%),45 first transplant (75%) and 42 (70%) received a kidney from deceased donor. 34 pts never presented AR episodes while 26 did. 20/26 (77%) of AR were diagnosed in the first 3 weeks after transplantation (median 13 days). Day 7 protocol biopsies (PB) showed AR in 12/26 (46%): 10 (85%) ABMR and 2 (15%) T-cell-mediated rejection (TCMR). The IB (n=18) done at a median of 11 days from the PB (range 3-112), showed AR in another 14 pts (56%): 10(71%) ABMR and 4 (29%) TCMR, as presented in Table 1 Pre-Tx mean MFI in ABMR pts did not differ among PB: 6001 (1596-11181) vs IB 2304 (840-14600)(p=NS). It also did not differ at the time of biopsy (2823 vs. 2277 in PB vs IB, respectively; p=NS). Patients with early ABMR diagnosis at PB had a trend to higher long-term MDRD (49±12mL/min) compared to patients with ABMR at IB (41±11mL/min) and similar to the whole non-ABMR patients (50±17mL/min). In conclusion, protocol biopsy is useful to diagnosis ABMR as early as in the first week pos-Tx. Early recognition of ABMR allows earlier treatment and possibly better long-term graft function in sensitized patients.- C4d staining in post-reperfusion renal biopsy is not useful for the early detection of antibody-mediated rejection when CDC crossmatching is negative(2011) DAVID-NETO, Elias; DAVID, Daisa S. R.; GINANI, Giordano F.; RODRIGUES, Helcio; SOUZA, Patricia S.; CASTRO, Maria Cristina R.; KANASHIRO, Hideki; SAITO, Fernando; FALCI JR., Renato; ANTONOPOULOS, Ioannis M.; PIOVESAN, Afonso Celso; NAHAS, William C.Background. Sensitized patients (pts) may develop acute antibody-mediated rejection (AMR) due to preformed donor-specific antibodies, undetected by pre-transplant complement-dependent cytotoxicity (CDC) crossmatch (XM). We hypothesized that C4d staining in 1-h post-reperfusion biopsies (1-h Bx) could detect early complement activation in the renal allograft due to preformed donor-specific antibodies. Methods. To test this hypothesis, renal transplants (n = 229) performed between June 2005 and December 2007 were entered into a prospective study of 1-h Bx and stained for C4d by immunofluorescence. Transplants were performed against a negative T-cell CDC-XM with the exception of three cases with a positive B-cell XM. Results. All 229 1-h Bx stained negative for C4d. Fourteen pts (6%) developed AMR. None of the 14 protocol 1-h Bx stained positive for C4d in peritubular capillaries (PTC). However, all indication biopsies-that diagnosed AMR-performed at a median of 8 days after transplantation stained for C4d in PTC. Conclusions. These data show that C4d staining in 1-h Bx is, in general, not useful for the early detection of AMR when CDC-XM is negative.
conferenceObject Microcirculation Inflammation in Early Surveillance Renal Biopsy in Sensitized Patients Did Not Correlate With Graft Outcome(2015) SOUZA, P.; MACHADO, D.; DAVID, D.; BEZERRA, G.; PAULA, F. Jota de; RODRIGES, H.; NAHAS, W.; DAVID NETO, E.; CASTRO, M.- 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.