Banff 2013 meeting report: inclusion of c4d-negative antibody-mediated rejection and antibody-associated arterial lesions.

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.

Non-human leukocyte antigen antibodies reactive with endothelial cells could be involved in early loss of renal allografts.

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.

Recommendations for use of marginal donors in heart transplantation: Brazilian Association of Organs Transplantation guideline.

The high prevalence of heart failure has increased the candidate list for heart transplantation; however, there is a shortage of viable donated organs, which is responsible for the high mortality of patients awaiting a transplantation. Because the marginal donor presents additional risk factors, it is not considered to be an ideal donor. The use of a marginal donor is only justified in situations when the risk of patient death due to heart disease is greater than that offered by the donor. These recommendations sought to expand the supply of donors, consequently increasing the transplant rate. We selected articles based on robust evidence to provide a substratum to develop recommendations for donors who exceed the traditional acceptance criteria. Recipient survival in the immediate postoperative period is intimately linked to allograft quality. Primary allograft failure is responsible for 38% to 40% of immediate deaths after heart transplantation: therefore; marginal donor selection must be more rigorous to not increase the surgical risk. The main donor risk factors with the respective evidence levels are: cancer in the donor (B), female donor (B), donor death due to hemorrhagic stroke (B), donor age above 50 years (relative risk [RR] = 1.5) (B), weight mismatch between donor and recipient < 0.8 (RR = 1.3) (B), ischemia > 240 minutes (RR = 1.2) (B), left ventricular dysfunction with ejection fraction below 45% (B), and use of high doses of vasoactive drugs (dopamine > 15 mg/kg·min) (B). Factors that impact recipient mortality are: age over 50 years (RR = 1.5); allograft harvest at a distance; adult recipient weighing more than 20% of the donor; high doses of vasoactive drugs (dopamine greater than 15 mg/kg·min) and ischemic time >4 hours. The use of a marginal donor is only justified when it is able to increase life expectancy compared with clinical treatment, albeit the outcomes are interior to those using an ideal donor.

Incidence of delayed graft function in cadaveric kidney transplants in Brazil: a multicenter analysis.

To evaluate the frequency of delayed graft function (DGF) in kidney transplant centers in Brazil, we sent a questionnaire requesting information on the number of cadaveric donor kidney transplants performed during the years 2000, 2001, and 2002, the number of early nonfunctioning grafts, and the number of patients on dialysis during the first posttransplant week with subsequent recovery. Among all centers performing more than 50 kidney transplants during the last year of evaluation, 6, performing 612 cadaveric kidney transplants during the study period, replied to the questionnaire. Sixty procedures (9.7%) resulted in nonfunctioning grafts, while 312 (55.6%) patients required dialysis during the first Ptx week: 216 (53.9%) in 2000, 189 (62.3%) in 2001, and 216 (51.6%) in 2002. The frequency of DGF during the study period was higher than that noted by several previous foreign studies. To better evaluate the possible causes of this finding, a more extensive and focused study is warranted.

Identifying cyclosporine blood levels associated with the prevention of renal transplant rejection: a single-center, randomized prospective study.

Multiple-drug therapy may allow reduced individual drug doses with fewer side effects. Blood levels of cyclosporine (CsA) necessary to avoid rejection may vary with different drug combinations. Fifty-eight kidney transplant patients were randomized into two groups: 25 subjects were assigned to the 4-hour area under the curve (AUC(0-4)) Cohort-the "high arm" (4500 to 5500 ng . h/mL)--1 and 33 to the AUC(0-4) "low arm" (2400 to 3400 ng . h/mL). After CsA introduction, AUC(0-4) was drawn on days 4, 7, 14, 21, 28, 42, 56, 70, 84, 90. We compared the proportion of rejection versus rejection-free patients, according to the CsA exposure. Logistic regression analysis showed that an AUC(0-4) of > or =4000 ng . h/mL or a 2-hour cyclosporine level (C(2)) of > or =1450 ng/mL predicted a rejection-free course among patients not receiving induction therapy. When either basiliximab or thymoglobulin was administered, a C(2) and AUC(0-4) of 1043 +/- 151 ng/mL or 3146 +/- 262 ng . h/mL, respectively, were associated with a rejection-free course. Our findings confirm the need for different CsA levels to prevent rejection according to induction therapy. Induction with either basiliximab or thymoglobulin allows reduced CsA levels during the first 3 months after renal transplantation.

Induction versus noninduction therapy in kidney transplantation: considering different PRA levels and different induction therapies.

To evaluate the rate of acute cellular rejection (ACR) and long-term results in different levels of anti-HLA sensitization, using noninduction or different induction therapies, 763 patients who underwent transplantation from January 1995 to December 2001 were evaluated: 213 patients received induction therapy, 71 received Thymoglobulin (Thymo), 66 Simulect, and 44 OKT3. Follow-up time was at least 1 year for all groups. The Simulect group included older recipients and the OKT3 group had more female patients. Simulect and OKT3 groups had more black patients; Thymo and OKT3 groups had more retransplantations. PRA was low in the noninduction group (mean, 7%) and about the same in the Simulect and Thymo groups (mean, 30%). OKT3 was the most sensitized group (mean = 59%). Dialysis during the first posttransplantation week was more frequent among the induction groups (43% vs 65%; P <.005). Fewer patients experienced rejection episodes in the Thymo group (20% vs 50%; P =.02). Patients were classified according to their level of sensitization, and the Thymo group showed the lower rejection rates in all levels (mean, 20%; P =.001). When analyzing PRA >50%, the Thymo group showed lower rejection rates (12% vs 50%; P =.02). At this level of sensitization, there was no significant difference on graft loss and death with a functioning graft. There was a trend to more cytomegalovirus (CMV) disease in the Thymo group (33% vs 23%; P =.08). Two PTLD were diagnosed, both in the noninduction group. Renal function was better in the Thymo group (1.3 mg/dL). In conclusion, Thymo showed lower ACR rates in all PRA groups. No significant differences in CMV infection, tumors, and patient survival were observed.

Comparaçäo entre diagnósticos clínicos e histológicos no pós-transplante renal / Comparison between clinical and histological diagnosis in kidney post-transplantation period

Objetivo. Para determinar o acerto obtido pelos diagnósticos efetuados em uma unidade de transplante renal, foram analisados 40 episódios de disfunçao renal aguda que ocorreram no período pós-transplante. Métodos. Os pacientes foram submetidos a biópsia renal por ocasiao do episódio de insuficiência renal ao mesmo tempo em que o diagnóstico clínico era realizado pelos membros da equipe. Resultados. Foram realizados 19 diagnósticos de necrose tubular aguda (NTA), 18 de rejeiçao celular aguda (RCA), dois de rejeiçao humoral (RH) e um de defrotoxicidade (NTX) pela ciclosporina A (CyA). O diagnóstico de NTA foi confirmado pela histologia em 84,21 por cento, o de RCA, em 83,33 por cento, o de RH em 100 por cento e o único diagnóstico de NTX realizado se apresentou como NTA à biópsia. No total, a clínica foi concordante com a histologia em 82,5 por cento das vezes. Conclusao. Os autores concluíram que esxiste uma boa acurácia nos diagnósticos clínicos de RCA, NTA e RH realizados em um centro experiente em transplante renal.

Uso do anticorpo monoclonal OKT3 em rejeiçöes graves / Use of OKT3 monoclonal antibody in grave rejections

Com o objetivo de avaliar a reposta ao anticorpo monoclonal OKT3 nas rejeiçöes celulares graves, estudamos 14 pacientes com rejeiçöes resistentes a tratamento com pelo menos uma pulsoterapia, 13 dos quais apresentando biópsia renal prévia. Cinco deles eram receptores de rim de cadáver e nove de doador vivo. Os adultos receberam 5mg de OKT3 e as crianças 2,5mg por dez dias. A monitorizaçäo de células T3 foi realizada em nove pacientes. Onze pacientes tiveram revertido o episódio de rejeiçäo; nos outros três casos, em que näo houve resposta, os rins foram perdidos: dois por vasculopatia aguda e um por rejeiçäo celular. Um deles apresentou reversäo parcial com posterior perda por vasculopatia. Dos 11 pacientes que tiveram o episódio revertido, 10 foram biopsiados previamente e apresentavam: RCA em quatro casos, RCA e NTA em três RCA e VAT em outros três. Em cinco pacientes que apresentavam vasculopatia, o OKT3 foi capaz de reverter o episódio em três ocasiöes. Os dois casos sem resposta tratavam-se de um quarto transplante com três perdas imunológicas prévias e um paciente com prova cruzada antilinfócitos B e antimonócitos positiva. Apenas um caso de RCA pura näo respondeu ao tratamento, provavelmente por se tratar de paciente com cross-match histórico positivo contra linfócitos T e anti-B e monócitos atuais positivos. A reversäo dos quadros de RCA pura foi igual a 87,5%. No total, incluindo as rejeiçöes com componente vascular, a taxa de reversäo foi de 78%. Concluímos que o OKT3 é um potente imunossupressor, capaz de reverter rejeiçöes graves, inclusive muitas das que se apresentam com componente vascular importante. É uma arma terapêutica que näo deve ser descartada nos casos de vasculopatia aguda do transplante

Citologia aspirativa no pós-transplante renal: resultados da primeira experiência brasileira / Aspiration cytology after kidney transplants: results of the first brazilian experience

A citologia aspirativa de rim transplantado, utilizada em vários centros de transplante, tem permitido a análise repetida do tecido renal, sem ocasionar desconforto para o paciente e com menor risco do que o imposto pela biópsia renal Revela-se muito útil na diferenciaçäo entre rejeiçäo celular aguda (RCA), necrose tubular aguda (NTA) e nefrotoxicidade pela ciclosporina, monitorizando o transplante, sobretudo nos três primeiros meses. Entre março de 1987 e junho de 1988, realizamos 231 punçöes em 42 pacientes. Destas, 158 (71,7%) proporcionaram material representativo para análise. Nesses pacientes, foram diagnosticados 20 episódios de RCA, todos confirmados pela evoluçäo clínica e laboratorial. Em oito ocasiöes, o diagnóstico citológico precedeu o aparecimento de sinais clínicos de rejeiçäo. Em dois casos, detectou-se tendência a cronificaçäo do processo. Tivemos somente quatro falsos negativos e um falso positivo para RCA. Em 11 casos, diagnosticou-se NTA pura e, em dez vezes, lesäo tubular associada a nefrotoxicidade pela cilosporina. Nenhuma complicaçäo decorrente do método foi observada. Concluímos que A citologia aspirativa, por ser inócua, de fácil execuçäo, poder ser repetida com freqüência e por apresentar alta correlaçäo clínica, deve se incluída na monitorizaçäo rotineira do pós-transplante renal

Effect of posture and physical activity on urinary protein excretion by patients with glomerular proteinuria diseases

The rate of urinary protein excretion (Uprot.V) was evaluated in 20 patients with massive proteinuria caused by various histopathological types of glomerular disease. Measurements were made during five consecutive periods: period A (overnight bed res) and periods B, C, D and E corresponding to normal everyday upright physical activity. Mean Uprot.V was significantly lower during period A (8.2 + or - 1.3 mg/min, mean + or - SEM) than during all the periods of physical activity (11.8 + or - 1.8 mg/min). For 5/20 patients, physical activity induced a mean percent increase of 340 + or - 200% and for 11 an increase of 51 + or - 7% was observed. Only in 4 patients was the rate of urinary protein excretion unaffected or decreased on the average by -20 + or - 9% during physical activity