RESUMO
Hahnemann University Hospital has performed 120 kidney transplantations in human immunodeficiency virus (HIV)-positive individuals during the last 16 years. Our patient population represents â¼10% of the entire US population of HIV-positive kidney recipients. In our earlier years of HIV transplantation, we noted increased rejection rates, often leading to graft failure. We have established a multidisciplinary team and over the years have made substantial protocol modifications based on lessons learned. These modifications affected our approach to candidate evaluation, donor selection, perioperative immunosuppression, and posttransplantation monitoring and resulted in excellent posttransplantation outcomes, including 100% patient and graft survival at 1 year and patient and graft survival at 3 years of 100% and 96%, respectively. We present key clinical data, including a granular patient-level analysis of the associations of antiretroviral therapy regimens with long-term survival, cellular and antibody-mediated rejection rates, and the causes of allograft failures. In summary, we provide details on the evolution of our approach to HIV transplantation during the last 16 years, including strategies that may improve outcomes among HIV-positive kidney transplantation candidates throughout the United States.
Assuntos
Soropositividade para HIV/complicações , Falência Renal Crônica/complicações , Falência Renal Crônica/cirurgia , Transplante de Rim , Idoso , Feminino , Hospitais Universitários , Humanos , Masculino , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: The 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. METHODS: The 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 = 135.5 days post-transplant). RESULTS: Interstitial CD56+ cells had an increased expression for glomerulitis (g ≥ 1) (P = 0.02) and peritubular capillaritis (ptc ≥ 2) (P = 0.003) presence. It was noted that interstitial CD56 + cells with mean above 0.56 cells/mm2 had worse allograft survival. CD56+ cells in the interstitial compartment with mean less than or equal to 0.56cells/mm2 was related with absence or mild peritubular capillaritis (P = 0.012) and mean above 0.56 cells/mm2 , 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. CONCLUSIONS: The study findings showed that CD56+ cell infiltrated in the interstitial compartment was significantly associated with microcirculation injury scores, especially the glomerulitis, and graft survival.
Assuntos
Antígeno CD56/análise , Rejeição de Enxerto , Sobrevivência de Enxerto , Transplante de Rim/efeitos adversos , Receptores de IgG/análise , Doença Aguda , Adolescente , Adulto , Biópsia , Feminino , Proteínas Ligadas por GPI/análise , Humanos , Masculino , Microcirculação , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Vascularized bone marrow transplantation (VBMT) appears to promote tolerance for vascularized composite allotransplantation (VCA). However, it is unclear whether VBMT is critical for tolerance induction and, if so, whether there is a finite amount of VCA that VBMT can support. We investigated this with a novel VCA combined flap model incorporating full-thickness hemiabdominal wall and hindlimb osteomyocutaneous (HAW/HLOMC) flaps. Effects of allograft mass (AM) and VBMT on VCA outcome were studied by comparing HAW/HLOMC VCAs with fully MHC-mismatched BN donors and Lewis recipients. Control groups did not receive treatments following transplantation. Treatment groups received a short course of cyclosporine A (CsA), antilymphocyte serum, and three doses of adipocyte-derived stem cells (POD 1, 8, and 15). The results showed that all flaps in control allogeneic groups rejected soon after VCAs. Treatment significantly prolonged allograft survival. Three of eight recipients in HLOMC treatment group had allografts survive long-term and developed donor-specific tolerance. Significantly higher peripheral chimerism was observed in HLOMC than other groups. It is concluded that the relative amount of AM to VBMT is a critical factor influencing long-term allograft survival. Accordingly, VBMT content compared with VCA mass may be an important consideration for VCA in humans.
Assuntos
Parede Abdominal/cirurgia , Transplante de Medula Óssea/métodos , Aloenxertos Compostos , Membro Posterior/cirurgia , Retalhos Cirúrgicos , Alotransplante de Tecidos Compostos Vascularizados/métodos , Animais , Medula Óssea/irrigação sanguínea , Medula Óssea/imunologia , Estudos de Viabilidade , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Tolerância Imunológica , Imunossupressores/uso terapêutico , Teste de Cultura Mista de Linfócitos , Subpopulações de Linfócitos/imunologia , Masculino , Tamanho do Órgão , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Transplante de Pele , Cauda , Quimeras de TransplanteRESUMO
Experimental data and few clinical non-randomized studies have shown that inhibition of the renin-angiotensin system by angiotensin-converting enzyme (ACE) associated or not with the use of mycophenolate mofetil (MMF) could delay or even halt the progression of chronic allograft nephropathy (CAN). In this retrospective historical study, we investigated whether ACE inhibition (ACEI) associated or not with the use of MMF has the same effect in humans as in experimental studies and what factors are associated with a clinical response. A total of 160 transplant patients with biopsy-proven CAN were enrolled. Eighty-one of them were on ACE therapy (G1) and 80 on ACEI_free therapy (G2). Patients were further stratified for the use of MMF. G1 patients showed a marked decrease in proteinuria and stabilized serum creatinine with time. Five-year graft survival after CAN diagnosis was more frequent in G1 (86.9 vs 67.7 percent; P < 0.05). In patients on ACEI-free therapy, the use of MMF was associated with better graft survival. The use of ACEI therapy protected 79 percent of the patients against graft loss (OR = 0.079, 95 percentCI = 0.015-0.426; P = 0.003). ACEI and MMF or the use of MMF alone after CAN diagnosis conferred protection against graft loss. This finding is well correlated with experimental studies in which ACEI and MMF interrupt the progression of chronic allograft dysfunction and injury. The use of ACEI alone or in combination with MMF significantly reduced proteinuria and stabilized serum creatinine, consequently improving renal allograft survival.
Assuntos
Adulto , Feminino , Humanos , Masculino , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Rejeição de Enxerto/tratamento farmacológico , Imunossupressores/administração & dosagem , Transplante de Rim , Ácido Micofenólico/análogos & derivados , Proteinúria/tratamento farmacológico , Biópsia , Doença Crônica , Creatinina/sangue , Sinergismo Farmacológico , Quimioterapia Combinada , Rejeição de Enxerto/patologia , Rim/patologia , Ácido Micofenólico/administração & dosagem , Proteinúria/urina , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
A major problem in renal transplantation is identifying a grading system that can predict long-term graft survival. The present study determined the extent to which the two existing grading systems (Banff 97 and chronic allograft damage index, CADI) correlate with each other and with graft loss. A total of 161 transplant patient biopsies with chronic allograft nephropathy (CAN) were studied. The samples were coded and evaluated blindly by two pathologists using the two grading systems. Logistic regression analyses were used to evaluate the best predictor index for renal allograft loss. Patients with higher Banff 97 and CADI scores had higher rates of graft loss. Moreover, these measures also correlated with worse renal function and higher proteinuria levels at the time of CAN diagnosis. Logistic regression analyses showed that the use of angiotensin-converting enzyme inhibitor (ACEI), hepatitis C virus (HCV), tubular atrophy, and the use of mycophenolate mofetil (MMF) were associated with graft loss in the CADI, while the use of ACEI, HCV, moderate interstitial fibrosis and tubular atrophy and the use of MMF were associated in the Banff 97 index. Although Banff 97 and CADI analyze different parameters in different renal compartments, only some isolated parameters correlated with graft loss. This suggests that we need to review the CAN grading systems in order to devise a system that includes all parameters able to predict long-term graft survival, including chronic glomerulopathy, glomerular sclerosis, vascular changes, and severity of chronic interstitial fibrosis and tubular atrophy.