Strategies to keep kidney transplant alive amid the SARS-CoV-2 pandemic

SUMMARY OBJECTIVE: This study aims to describe the result of the strategies adopted to maintain the transplant program amid the COVID-19 pandemic. METHODS: Since March 2020, several measures have been adopted sequentially, including the compulsory use of personal protective equipment and the real-time polymerase chain reaction testing of collaborators, symptomatic patients, potential deceased donors, candidates for recipients, and in-hospital readmissions, regardless of symptoms. The living-donor transplantation was restricted to exceptional cases. RESULTS: Among 1013 health professionals, 201 cases of COVID-19 were confirmed between March and August 2020, with no severe cases reported. In this period, we observed a 19% institutional increase in the number of transplants from deceased donors compared with that observed in the same period in 2019. There was no donor-derived severe acute respiratory syndrome virus (SARS-CoV-2) infection. Four COVID-19-positive patients underwent transplantation; after 28 days, all were alive and with functioning allograft. Among the 11,875 already transplanted patients being followed up, there were 546 individuals with confirmed diagnosis, 372 who required hospitalization, and 167 on mechanical ventilation, resulting in a 27% mortality rate. CONCLUSIONS: These data confirm that the adoption of sequential and coordinated measures amid the pandemic was able to successfully maintain the transplant program and ensure the safety of health professionals and transplanted patients who were already in follow-up.

The influence of clinical, environmental, and socioeconomic factors on five-year patient survival after kidney transplantation / A influência de fatores clínicos, ambientais e socioeconômicos na sobrevida de cinco anos após o transplante renal

ABSTRACT Introduction: The risk of death after kidney transplant is associated with the age of the recipient, presence of comorbidities, socioeconomic status, local environmental characteristics and access to health care. Objective: To investigate the causes and risk factors associated with death during the first 5 years after kidney transplantation. Methods: This was a single-center, retrospective, matched case-control study. Results: Using a consecutive cohort of 1,873 kidney transplant recipients from January 1st 2007 to December 31st 2009, there were 162 deaths (case group), corresponding to 5-year patient survival of 91.4%. Of these deaths, 25% occurred during the first 3 months after transplant. The most prevalent cause of death was infectious (53%) followed by cardiovascular (24%). Risk factors associated with death were history of diabetes, dialysis type and time, unemployment, delayed graft function, number of visits to center, number of hospitalizations, and duration of hospital stay. After multivariate analysis, only time on dialysis, number of visits to center, and days in hospital were still associated with death. Patients who died had a non-significant higher number of treated acute rejection episodes (38% vs. 29%, p = 0.078), higher mean number of adverse events per patient (5.1 ± 3.8 vs. 3.8 ± 2.9, p = 0.194), and lower mean eGFR at 3 months (50.8 ± 25.1 vs. 56.7 ± 20.7, p = 0.137) and 48 months (45.9 ± 23.8 vs. 58.5 ± 20.2, p = 0.368). Conclusion: This analysis confirmed that in this population, infection is the leading cause of mortality over the first 5 years after kidney transplantation. Several demographic and socioeconomic risk factors were associated with death, most of which are not readily modifiable.

RESUMO Introdução: O risco de óbito após transplante renal está associado à idade do receptor, presença de comorbidades, condição socioeconômica, às características ambientais locais e ao acesso a serviços de atenção à saúde. Objetivo: Investigar as causas e fatores de risco associados ao óbito nos primeiros cinco anos após o transplante renal. Métodos: Este é um estudo unicêntrico retrospectivo com pareamento dos grupos caso e controle. Resultados: Em uma coorte consecutiva de 1.873 receptores de transplante renal atendidos de 1/1/2007 a 31/12/2009 foram registrados 162 óbitos (grupo caso), correspondendo a uma taxa de sobrevida após cinco anos de 91,4%. Dos óbitos registrados, 25% ocorreram nos primeiros três meses após o transplante. A causa de óbito mais prevalente foi infecção (53%), seguida de doença cardiovascular (24%). Os fatores de risco associados a mortalidade foram histórico de diabetes, tipo e tempo em diálise, desemprego, função tardia do enxerto, número de consultas, número de hospitalizações e tempo de internação hospitalar. Após análise multivariada, apenas o tempo em diálise, o número de consultas e dias de internação permaneceram associados a mortalidade. Os pacientes que foram a óbito tiveram um número não significativamente maior de tratamentos de episódios de rejeição aguda (38% vs. 29%; p = 0,078), maior número médio de eventos adversos por paciente (5,1 ± 3,8 vs. 3,8 ± 2,9; p = 0,194) e TFGe média mais baixa aos três meses (50,8 ± 25,1 vs. 56,7 ± 20,7; p = 0,137) e 48 meses (45,9 ± 23,8 vs. 58,5 ± 20,2; p = 0,368). Conclusão: A presente análise confirmou que nessa população, a infecção foi a principal causa de mortalidade nos primeiros cinco anos após transplante renal. Vários fatores de risco demográficos e socioeconômicos foram associados a mortalidade, a maioria não prontamente modificável.

The current burden of cytomegalovirus infection in kidney transplant recipients receiving no pharmacological prophylaxis / O fardo atual da infecção por citomegalovírus em receptores de transplante renal que não recebem profilaxia farmacológica

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.

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.

Targeted preemptive therapy according to perceived risk of CMV infection after kidney transplantation

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.

Uso de everolimo de novo em receptores de transplante renal com doador vivo HLA idêntico / De novo everolimus for recipients of kidney transplants from HLA identical donors

Resumo Introdução: Receptores de rim de doadores vivos HLA-idêntico apresentam menor risco para rejeição aguda e maior sobrevida do enxerto, quando comparado a outros tipos de transplante. Um regime imunossupressor sem inibidor de calcineurina (ICN) pode melhorar ainda mais esses resultados, através da redução de eventos cardiovasculares, metabólicos e tóxicos secundários a esse fármaco. Objetivo: Avaliar eficácia e segurança do novo tratamento imunossupressor com suspensão planejada do ICN. Métodos: Estudo prospectivo, aberto, braço único de tratamento em único centro para avaliar resultados do transplante renal HLA-idêntico em pacientes que recebem everolimo (EVR), tacrolimo (TAC) e corticoide, seguido da descontinuação do TAC 30 dias pós-transplante. Após análise interina de eficácia, a descontinuação do TAC foi postergada para o terceiro mês pós-transplante, através de emenda ao protocolo. Resultados: Trinta e nove pacientes foram incluídos. Apesar de as médias das concentrações de TAC e EVR terem respeitado os intervalos propostos, cinco pacientes tiveram rejeição aguda comprovada por biópsia e um paciente apresentou um episódio de glomerulite com depósitos de C4D. Esse resultado demandou o fim das inclusões. A proporção de pacientes com proteinúria > 0.5g/L não atingiu mais que 22% dos pacientes em nenhuma visita. Os eventos adversos mais frequentes foram relacionados ao uso de EVR: úlceras orais, dislipidemia e edema periférico. Conclusão: O regime proposto não foi eficaz para essa população, principalmente pela alta incidência de rejeição aguda. O perfil de segurança mostrou que a exposição prolongada a altas concentrações sanguíneas de EVR aumenta a incidência dos eventos adversos relacionados ao fármaco.

Abstract Introduction: Kidney transplant recipients from HLA-identical living donor have lower risk of acute rejection and greater graft survival compared to other types of kidney transplantation. Immunosuppressive regimens without calcineurin inhibitors (CNI) can further improve these results by reducing cardiovascular, metabolic and toxic events related to this drug class. Objective: This study aimed to evaluate efficacy and safety of a new immunosuppressive regimen with planned suspension of CNI. Methods: This was a prospective, single center and single treatment arm study to evaluate HLA-identical kidney transplant recipients receiving everolimus (EVR), tacrolimus (TAC) and corticosteroids, followed by TAC discontinuation 30 days after transplantation. TAC discontinuation was later postponed to the third month after an interim efficacy analysis. Results: Thirty-nine patients were included. Although mean TAC and EVR blood concentrations have remained within the proposed therapeutic ranges, five patients had biopsy-proven acute rejection and one patient had an episode of C4D-positive glomerulitis. This result led to the end of the inclusions. Interestingly, the proportion of patients with proteinuria greater than 0.5 g/L has not reached more than 22% of patients in any visit. Adverse events related to EVR use were the most incident in this population: oral ulcers, dyslipidemia and peripheral edema. Conclusion: The proposed scheme was not effective for this population, particularly due to a high incidence of acute rejection. Safety profile showed that prolonged exposure to a high concentration of blood EVR increases the incidence of adverse events related to this drug.

Intracavernous injection in the treatment of erectile dysfunction after radical prostatectomy: an observational study

CONTEXT: Despite the recent improvements in performing radical retropubic prostatectomy that have led to a considerable decrease in the complication rate, erectile dysfunction still represents a major problem. Moreover, less invasive treatment options that are emerging for erectile dysfunction have not shown satisfactory results in managing these patients. OBJECTIVE: To study the efficacy and side effects of self-injection therapy in the treatment of men who had become impotent after undergoing radical prostatectomy due to prostate cancer, over a study period of 96 months. DESIGN: Observational study. SETTING: University Referral Center. PARTICIPANTS: 168 patients with erectile dysfunction, aged 43 to 78 years old, who underwent radical retropubic prostatectomy due to localized prostate cancer. PROCEDURES: The patients were treated with self-injection therapy using papaverine, phentolamine and prostaglandin E1, at home. RESULTS: This study showed an acceptable 94.6 percent success rate, with no life-threatening complications. In addition to this, our series presented a 13.1 percent cure rate with this therapy. CONCLUSION: Self-injection therapy with papaverine, phentolamine and prostaglandin E1 is effective and safe in the treatment of erectile dysfunction after radical prostatectomy