Resumo A infecção por citomegalovírus (CMV) no transplante renal mudou seu espectro clínico, principalmente devido à atual e mais efetiva imunossupressão. Na ausência de estratégias preventivas, está associado a significativa morbimortalidade. Objetivo: este estudo avaliou a incidência de eventos de CMV e seu efeito nos desfechos do transplante renal em receptores sem profilaxia farmacológica ou tratamento preventivo direcionado. Resultados: A coorte do estudo envolveu 802 receptores de transplantes de rim entre 30/04/2014 e 30/04/2015. A maioria recebeu indução com globulina anti-timocitária (81,5%), tacrolimus e prednisona em combinação com micofenolato (46,3%) ou azatioprina (53,7%). A incidência global de eventos de CMV foi de 42% (58,6% de infecção e 41,4% de doença). Os pacientes com CMV apresentaram maior incidência de rejeição aguda do primeiro tratamento (19 vs. 11%, p = 0,001), em comparação com aqueles sem CMV, mas sem diferenças na perda de enxerto, morte ou perda de seguimento. A incidência de função retardada de enxerto foi maior (56% vs. 37%, p = 0,000) e a TFGe a 1 (41 ± 21 vs. 54 ± 28 ml/min, p = 0,000) e 12 meses (50 ± 19 vs. 61 ± 29 ml/min, p = 0.000) foram menores em pacientes com CMV. A idade dos receptores (OR = 1,03), a sorologia negativa para CMV (OR = 5,21) e o uso de micofenolato (OR = 1,67) foram associados ao aumento do risco de CMV. As alterações na imunossupressão foram mais frequentes em doentes com CMV (63% vs. 31%, p = 0,000). Conclusão: a incidência de eventos relacionados a CMV foi alta e associada a maior incidência de rejeição aguda e alterações na imunossupressão. Além dos fatores de risco tradicionais, a função renal com 1 mês foi associada de forma independente à infecção por CMV.

Abstract Cytomegalovirus (CMV) infection in kidney transplantation has changed its clinical spectrum, mostly due to the current and more effective immunosuppression. In the absence of preventive strategies it is associated with significant morbi-mortality. Objective: This study evaluated the incidence of CMV events and its effect on outcomes of kidney transplantation in recipients without pharmacological prophylaxis or targeted preemptive treatment. Results: The study cohort comprised 802 recipients of kidney transplants between 04/30/2014 and 04/30/2015. The majority received induction with anti-thymocyte globulin (81.5%), tacrolimus and prednisone in combination with either mycophenolate (46.3%) or azathioprine (53.7%). The overall incidence of CMV events was 42% (58.6% infection and 41.4% disease). Patients with CMV showed higher incidence of first treated acute rejection (19 vs. 11%, p = 0,001) compared with those without CMV but no differences in graft loss, death or loss to follow-up. The incidence of delayed graft function was higher (56% vs. 37%, p = 0.000) and the eGFR at 1 (41 ± 21 vs. 54 ± 28 ml/min, p = 0.000) and 12 months (50 ± 19 vs. 61 ± 29 ml/min, p = 0.000) were lower in patients with CMV. Recipients age (OR = 1.03), negative CMV serology (OR = 5.21) and use of mycophenolate (OR = 1.67) were associated with increased risk of CMV. Changes in immunosuppression was more often in patients with CMV (63% vs. 31%, p = 0.000). Conclusion: the incidence of CMV events was high and associated with higher incidence of acute rejection and changes in immunosuppression. Besides traditional risk factors, renal function at 1 month was independently associated with CMV infection.

ABSTRACT Background: The identification of the best strategy to manage cytomegalovirus infection is hampered by uncertainties regarding the risk/benefit ratios of universal prophylaxis versus preemptive therapy, the impact of indirect cytomegalovirus effects and the associated costs. This study investigated the efficacy and safety of targeted preemptive therapy according to perceived risk of cytomegalovirus infection after kidney transplantation. Methods: 144 adult kidney transplant recipients were enrolled in this 12-month study. None received cytomegalovirus pharmacological prophylaxis. Only high risk patients (positive donor/negative recipient (D+/R−), use of induction therapy with antithymocyte globulin, treatment of rejection) received preemptive therapy based on the result of pp65 antigenemia test. Low-risk patients with symptoms related to cytomegalovirus were screened for pp65 antigenemia and treatment initiated if confirmed cytomegalovirus disease. Blinded cytomegalovirus DNAemia was collected weekly during the first three months. Results: The incidence of cytomegalovirus infection was 34% and cytomegalovirus disease was 17%. The incidence was 25% in D+/R−, 69% in those receiving induction with rabbit antithymocite globulin (r-ATG), 46% in those treated for acute rejection, and 28% in low risk patients. By week 3 DNAemia was observed in 30% of patients who were not treated for cytomegalovirus infection/disease, and values ≥2.169 UI/mL showed 61% sensitivity and 85% specificity to detect cytomegalovirus disease (AUC = 0.849 ± 0.042, p < 0.001). Using multivariate analysis, only anti-thymocyte globulin induction was associated with cytomegalovirus infection/disease whereas only expanded donor criteria and renal function at 30 days were associated with renal function 12 months after transplantation. Conclusion: Targeted preemptive therapy in patients with perceived higher risk for cytomegalovirus infection/disease was effective in preventing severe clinical presentation, including tissue invasive and late cytomegalovirus infection. This strategy is associated with direct and indirect cost-savings.

Resumo Introdução: O número de pacientes idosos portadores de doença renal crônica aumenta progressivamente, desafiando os algoritmos de alocação, em um cenário de escassez de órgãos para transplante. Objetivo: Avaliar o impacto da idade sobre os resultados do transplante renal. Métodos: Foram analisados todos os 366 pacientes > 60 anos transplantados entre 1998-2010 versus um grupo controle de 366 pacientes mais jovens pareados por gênero, tipo de doador (vivo/falecido) e ano do transplante. Resultados: Diabetes mellitus (HR 1,5; IC 1,0-2,2; p = 0,031) e doador falecido (HR 1,7; IC 1,2-2,7; p = 0,013) se associaram independentemente a maior risco de óbito. Diabetes mellitus (HR 1,8; IC 1,2-2,6; p = 0,003) e priorização por acesso vascular (HR 2,9; IC 1,2-2,6; p < 0,001), mas não idade, foram fatores independentes de perda do enxerto renal. Conclusão: A idade avançada não teve impacto negativo no resultado do transplante quando excluído óbito do paciente como causa de perda do enxerto. A maior mortalidade entre a população senil esteve associada à maior frequência de comorbidades, em especial diabetes mellitus.

Abstract Introduction: The number of elderly patients with chronic kidney disease increases progressively, challenging the allocation algorithms in a scenario of organ shortage for transplantation. Objective: To evaluate the impact of age on patient and graft survival. Methods: Evolution of all 366 patients greater than 60 years transplanted between 1998 and 2010 was analyzed versus a control group of 366 younger patients matched for gender, type of donor (living or deceased) and year of transplantation. Results: Diabetes mellitus (HR 1.8; IC 1.2-2.6; p = 0,003) and prioritization (HR 2.9; IC 1.2-2.6; p < 0,001), but not age, were independent factors for kidney graft loss. Conclusion: Advanced age was not related to negative outcomes after kidney transplantation, after excluding recipient death as a cause of allograft loss. Higher mortality rate in this group was associated to a higher frequency of comorbidities, especially diabetes mellitus.

INTRODUÇÃO: Terapias de indução são usualmente utilizadas em receptores sensibilizados contra antígenos HLA, retransplantes e pacientes com risco de apresentar função tardia do enxerto (FTE). MÉTODO: Estudo retrospectivo com objetivo de avaliar os desfechos do transplante renal com doador falecido em pacientes que receberam indução com alentuzumabe (n = 9). Os pacientes do grupo controle, pareados conforme idade do receptor, tempo em diálise e tempo de isquemia fria, receberam timoglobulina (n = 18). RESULTADOS: Não houve diferença nas características demográficas entre os grupos. A idade média dos receptores foi de 47 anos e dos doadores, de 59 anos. Entre os doadores, 67% apresentavam critério expandido. A incidência de FTE foi de 55% e 56%, respectivamente. Ao final do primeiro ano, não houve diferença nas sobrevidas livre de rejeição aguda comprovada por biópsia (67,0% e 84,6%, p = 0,26), do paciente (83,3% e 81,2%; p = 0,63), do enxerto (62,5% e 66,7%; p = 0,82), do enxerto com óbito censorado (62,5% e 76,6%; p = 0,73) e na função renal (depuração de creatinina: 61,6 ± 18,2 versus 52,7 ± 26,1 mL/min, p = 0,503). Houve maior redução na contagem de linfócitos no sangue periférico no grupo alentuzumabe (dia 14:172 ± 129 versus 390 ± 195 N/mm³, p < 0,05; dia 30: 135 ± 78 versus 263±112 N/mm³, p < 0,05), porém com retorno mais rápido a valores normais após o transplante (dia 90: 683 ± 367 versus 282 ± 72 N/mm³, p < 0,05; dia 360: 1269 ± 806 versus 690±444 N/mm³, p < 0,05). O custo do tratamento com alentuzumabe foi de R$ 1.388,00, enquanto que o custo médio com timoglobulina foi de R$ 7.398,00. CONCLUSÃO: Essa experiência com alentuzumabe não demonstrou eficácia e/ou segurança superiores aos regimes com timoglobulina, apesar do custo ser em média cinco vezes menor.

INTRODUCTION: Induction therapy has been used in sensitized patients, re-transplants, and in patients who have high risk to delayed graft function (DGF) after renal transplantation. METHODS: Retrospective study with aim to compare transplant endpoints between recipients of deceased donors which have received induction with alemtuzumab (n = 9) versus thymoglobulin (n = 18). Patients were matched for age, duration of dialysis treatment and cold ischemia time. RESULTS: There were no differences at demographic characteristics. All patients received kidney grafts from deceased donors and 67% of these donors met the expanded criteria. The incidence of DFG was similar in alemtuzumab and thymoglobulin groups, 55% and 56%. At 12 months, rates of rejection free survival (67% versus 89%, p = 0,13), graft survival (62,5% versus 76,6%; p = 0,73), graft with death censored (62,5% versus 76,6%; p = 0,82) and patient survival (83,3% versus 81,2%; p = 0,63) were similar between the two groups. Viral infections and renal function were similar between groups. At the end of the first month, alemtuzumab patients displayed a fewer lymphocyte number (135 ± 78 versus 263 ± 112 N/mm³, p < 0,05) followed by a more rapid recovery after 3 months (day 90: 683 ± 367 versus 282 ± 72 N/mm³; p < 0,05). Cost associated with alemtuzumab and thymoglobulin inductions therapies were R$ 1,388.00 and R$ 7,398.00. CONCLUSION: In this cohort of patients, alemtuzumab induction showed efficacy and safety comparable to thymoglobulin but with significant cost reduction.