Pregnancy after kidney transplantation: 40 years single-center experience / Gestação após transplante renal: 40 anos de experiência em centro único

Abstract Background: Kidney transplantation (KT) improves quality of life, including fertility recovery. Objective: to describe outcomes of post-KT pregnancy and long-term patient and graft survival compared to a matched control group of female KT recipients who did not conceive. Methods: retrospective single-center case-control study with female KT recipients from 1977 to 2016, followed-up until 2019. Results: there were 1,253 female KT patients of childbearing age in the study period: 78 (6.2%) pregnant women (cases), with a total of 97 gestations. The median time from KT to conception was 53.0 (21.5 - 91.0) months. Abortion rate was 41% (spontaneous 21.6%, therapeutic 19.6%), preterm delivery, 32%, and at term delivery, 24%. Pre-eclampsia (PE) occurred in 42% of pregnancies that reached at least 20 weeks. The presence of 2 or more risk factors for poor pregnancy outcomes was significantly associated with abortions [OR 3.33 (95%CI 1.43 - 7.75), p = 0.007] and with kidney graft loss in 2 years. The matched control group of 78 female KT patients was comparable on baseline creatinine [1.2 (1.0 - 1.5) mg/dL in both groups, p = 0.95] and urine protein-to-creatinine ratio (UPCR) [0.27 (0.15 - 0.44) vs. 0.24 (0.02 - 0.30), p = 0.06]. Graft survival was higher in cases than in controls in 5 years (85.6% vs 71.5%, p = 0.012) and 10 years (71.9% vs 55.0%, p = 0.012) of follow-up. Conclusion: pregnancy can be successful after KT, but there are high rates of abortions and preterm deliveries. Pre-conception counseling is necessary, and should include ethical aspects.

Resumo Histórico: Transplante renal (TR) melhora qualidade de vida, incluindo recuperação da fertilidade. Objetivo: descrever desfechos gestacionais pós-TR e sobrevida de longo prazo da paciente e do enxerto renal comparada a um grupo controle pareado de receptoras de TR que não conceberam. Métodos: estudo retrospectivo caso-controle com receptoras de TR de 1977 a 2016, acompanhadas até 2019. Resultados: foram identificadas 1.253 receptoras de TR em idade fértil no período do estudo: 78 (6,2%) gestantes (casos), total de 97 gestações. Tempo mediano entre TR até concepção foi 53,0 (21,5 - 91,0) meses. Taxa de aborto foi 41% (espontâneo 21,6%, terapêutico 19,6%), parto prematuro, 32%, e a termo, 24%. Pré-eclâmpsia (PE) ocorreu em 42% das gestações que alcançaram pelo menos 20 semanas. Presença de 2 ou mais fatores de risco para desfechos gestacionais desfavoráveis foi significativamente associada a abortos [OR 3,33 (IC95% 1,43 - 7,75), p = 0,007] e perda de enxerto renal em 2 anos. O grupo controle de 78 mulheres com TR foi comparável na creatinina basal [1,2 (1,0 - 1,5) mg/dL nos dois grupos, p = 0,95] e na relação proteína/creatinina urinária (RPCU) [0,27 (0,15 - 0,44) vs. 0,24 (0,02 - 0,30), p = 0,06]. Sobrevida do enxerto foi maior nos casos que nos controles em 5 anos (85,6% vs. 71,5%, p = 0,012) e 10 anos (71,9% vs. 55,0%, p = 0,012) de acompanhamento. Conclusão: a gestação pode ser bem-sucedida após TR, mas existem altas taxas de abortos e partos prematuros. Aconselhamento pré-concepção é necessário e deve incluir aspectos éticos.

Waiting time for kidney transplantation based on calculated panel reactive antibodies: experience of a southern Brazilian center / Tempo de espera para transplante renal com base em painel de reatividade de anticorpos calculado: experiência de um centro do sul do Brasil

ABSTRACT Introduction: The aim of this study was to analyze the waiting list for kidney transplantation in our hospital according to candidate's panel reactive antibodies (cPRA) and its outcomes. Methods: One thousand six hundred forty patients who were on the waiting list between 2015 and 2019 were included. For the analysis, hazard ratios (HR) for transplant were estimated by Fine and Gray's regression model according to panel reactivity and HR for graft loss and death after transplantation. Results: The mean age was 45.39 ± 18.22 years. Male gender was predominant (61.2%), but the proportion decreased linearly with the increase in cPRA (p < 0.001). The distribution of patients according to panels were: 0% (n = 390), 1% - 49% (n = 517), 50% - 84% (n = 269), and ≥ 85% (n = 226). Transplantation was achieved in 85.5% of the sample within a median time of 8 months (CI 95%: 6.9 - 9.1). The estimated HRs for transplantation during the follow-up were 2.84 (95% CI: 2.51 - 3.34), 2.41(95%CI: 2.07 - 2.80), and 2.45(95%CI: 2.08 - 2.90) in the cPRA range of 0%, 1%-49%, and 50%-84%, respectively, compared to cPRA ≥ 85 (p < 0.001). After transplantation, the HR for graft loss was similar in the different cPRA groups, but the HR for death (0.46 95% CI 0.24-0.89 p = 0.022) was lower in the 0% cPRA group when adjusted for age, gender, and presence of donor specific antibodies (DSA). Conclusion: Patients with cPRA below 85% are more than twice as likely to receive a kidney transplantation with a shorter waiting time. The risk of graft loss after transplantation was similar in the different cPRA groups, and the adjusted risk of death was lower in nonsensitized recipients.

RESUMO Introdução: O objetivo foi analisar a lista de espera para transplante renal em nosso hospital segundo o painel de reatividade de anticorpos (PRAc) do candidato e seus desfechos. Métodos: Incluímos 1.640 pacientes em lista de espera entre 2015 e 2019. Para a análise, estimou-se a razão de risco (HR) para transplante pelo modelo de regressão de Fine e Gray conforme o painel de reatividade e HR para perda do enxerto e óbito após o transplante. Resultados: A idade média foi 45,39 ± 18,22 anos. Sexo masculino foi predominante (61,2%), mas a proporção diminuiu linearmente com o aumento do PRAc (p < 0,001). A distribuição de pacientes conforme os painéis foi: 0% (n = 390), 1% - 49% (n = 517), 50% - 84% (n = 269), e ≥85% (n = 226). O transplante foi realizado em 85,5% da amostra em tempo mediano de 8 meses (IC 95%: 6,9 - 9,1). As HRs estimadas para transplante durante o acompanhamento foram 2,84 (IC 95%: 2,51 - 3,34), 2,41 (IC 95%: 2,07 - 2,80) e 2,45 (IC 95%: 2,08 - 2,90) no intervalo de PRAc de 0%, 1%-49% e 50%-84%, respectivamente, comparadas com PRAc ≥ 85 (p < 0,001). Após o transplante, a HR para perda do enxerto foi semelhante nos diferentes grupos de PRAc, mas HR para óbito (0,46 IC 95% 0,24-0,89 p = 0,022) foi menor no grupo PRAc 0% quando ajustada para idade, sexo e presença de anticorpos doador específico (DSA). Conclusão: Pacientes com PRAc abaixo de 85% têm mais que o dobro de probabilidade de receber transplante renal com tempo de espera menor. Risco de perda do enxerto após o transplante foi semelhante nos diferentes grupos PRAc, e risco ajustado de óbito foi menor em receptores não sensibilizados.

Pregnancy after kidney transplantation: 40 years single-center experience.

BACKGROUND: Kidney transplantation (KT) improves quality of life, including fertility recovery. OBJECTIVE: to describe outcomes of post-KT pregnancy and long-term patient and graft survival compared to a matched control group of female KT recipients who did not conceive. METHODS: retrospective single-center case-control study with female KT recipients from 1977 to 2016, followed-up until 2019. RESULTS: there were 1,253 female KT patients of childbearing age in the study period: 78 (6.2%) pregnant women (cases), with a total of 97 gestations. The median time from KT to conception was 53.0 (21.5 - 91.0) months. Abortion rate was 41% (spontaneous 21.6%, therapeutic 19.6%), preterm delivery, 32%, and at term delivery, 24%. Pre-eclampsia (PE) occurred in 42% of pregnancies that reached at least 20 weeks. The presence of 2 or more risk factors for poor pregnancy outcomes was significantly associated with abortions [OR 3.33 (95%CI 1.43 - 7.75), p = 0.007] and with kidney graft loss in 2 years. The matched control group of 78 female KT patients was comparable on baseline creatinine [1.2 (1.0 - 1.5) mg/dL in both groups, p = 0.95] and urine protein-to-creatinine ratio (UPCR) [0.27 (0.15 - 0.44) vs. 0.24 (0.02 - 0.30), p = 0.06]. Graft survival was higher in cases than in controls in 5 years (85.6% vs 71.5%, p = 0.012) and 10 years (71.9% vs 55.0%, p = 0.012) of follow-up. CONCLUSION: pregnancy can be successful after KT, but there are high rates of abortions and preterm deliveries. Pre-conception counseling is necessary, and should include ethical aspects.

Waiting time for kidney transplantation based on calculated panel reactive antibodies: experience of a southern Brazilian center.

INTRODUCTION: The aim of this study was to analyze the waiting list for kidney transplantation in our hospital according to candidate's panel reactive antibodies (cPRA) and its outcomes. METHODS: One thousand six hundred forty patients who were on the waiting list between 2015 and 2019 were included. For the analysis, hazard ratios (HR) for transplant were estimated by Fine and Gray's regression model according to panel reactivity and HR for graft loss and death after transplantation. RESULTS: The mean age was 45.39 ± 18.22 years. Male gender was predominant (61.2%), but the proportion decreased linearly with the increase in cPRA (p < 0.001). The distribution of patients according to panels were: 0% (n = 390), 1% - 49% (n = 517), 50% - 84% (n = 269), and ≥ 85% (n = 226). Transplantation was achieved in 85.5% of the sample within a median time of 8 months (CI 95%: 6.9 - 9.1). The estimated HRs for transplantation during the follow-up were 2.84 (95% CI: 2.51 - 3.34), 2.41(95%CI: 2.07 - 2.80), and 2.45(95%CI: 2.08 - 2.90) in the cPRA range of 0%, 1%-49%, and 50%-84%, respectively, compared to cPRA ≥ 85 (p < 0.001). After transplantation, the HR for graft loss was similar in the different cPRA groups, but the HR for death (0.46 95% CI 0.24-0.89 p = 0.022) was lower in the 0% cPRA group when adjusted for age, gender, and presence of donor specific antibodies (DSA). CONCLUSION: Patients with cPRA below 85% are more than twice as likely to receive a kidney transplantation with a shorter waiting time. The risk of graft loss after transplantation was similar in the different cPRA groups, and the adjusted risk of death was lower in nonsensitized recipients.

Real-world effectiveness and safety of direct-acting antivirals for the treatment of hepatitis C virus in kidney and liver transplant recipients: experience of a large transplant center in Brazil.

Direct-acting antivirals are the gold-standard treatment for chronic HCV infections, but few studies have investigated their use on kidney and liver transplant recipients. We conducted a real-world study to evaluate the rates of sustained virological response with direct-acting antivirals in kidney and liver transplant recipients. Moreover, it also aimed to evaluate direct-acting antivirals (DAAs) interference with immunosuppressant levels and to describe the frequency of adverse events. As part of this retrospective observational cohort, we included adult patients that had undergone a kidney transplant (KT) or liver transplant (LT) at our center, had a chronic HCV infection, and were treated with DAAs from June 2016 to December 2021. A total of 165 patients were included in the analysis, divided in 108 KT and 57 LT recipients. HCV genotype 1 was more frequent in KT (58.4%), and genotype 3 was more prevalent in LT (57.9%) patients. Sustained virological response was achieved in 89.6% of patients. Adverse effects were reported by 36% of patients. There were significant interactions with immunosuppressants requiring dose adjustments. A total of three episodes of rejection were reported in KT recipients. In conclusion, DAA treatment resulted in high rates of SVR and was well tolerated in both kidney and liver transplant patients. Adverse events were frequent but not severe in most patients, with low treatment drop-out rates. Interactions with immunosuppressants need monitoring since dose adjustments may be required. Reporting real-life experiences is important to help build evidence for patient management in non-controlled environments.

Bioimpedanciometry in nutritional and hydration assessments in a single dialysis center / Bioimpedanciometria em avaliações nutricionais e de hidratação em um único centro de diálise

ABSTRACT Background: Bioimpedance analysis (BIA) has been demonstrated to add accuracy to nutritional and volume status assessments in dialysis (HD) patients. Aim: to describe a sample of dialysis patients from a single center on their demographics and BIA of volume distribution and nutritional status, and mortality during 12-month follow-up. Methods: prospective observational cohort study to evaluate vintage HD patients with single-frequency BIA. Results: we evaluated 82 patients, 29% over 65 years old. Elderly patients had higher ECW/TBW (0.51 vs. 0.44, p < 0.0001), and narrower phase angle (PhA) (4.9 vs. 6.4º, p < 0.0001). Fifteen patients (18.2%) died during follow-up, eight (53%) were elderly. Death was associated with age (62.6 vs. 50.2 years, p = 0.012), post-HD PhA (4.8 vs. 6.2º, p = 0.0001), and post-HD ECW/TBW (0.50 vs. 0.45, p = 0.015). The ROC curve analysis to predict mortality found ECW/TBW ≥ 0.47 and PhA ≤ 5.5º to have the best sensitivity and specificity. One-year patient survival was lower with post-HD ECW/TBW ≥ 0.47 (69.5% vs. 90.6%, p = 0.019), age ≥ 65 years (64.2%, vs. 86.2%, p = 0.029), and PhA ≤ 5.5º (68.2 vs. 91.0%, p = 0.002). Cox regression analysis demonstrated that PhA [HR 5.04 (95%CI 1.60-15.86), p = 0.006] remained associated with death after adjusting for age and ECW/TBW. Conclusion: BIA is useful in assessing volume distribution and nutrition in HD patients, and combined with clinical judgement, may help determine dry weight, especially in elderly patients. Narrower PhA and higher ECW/TBW after HD were associated with poorer one-year survival.

RESUMO Antecedentes: Análise de bioimpedância (BIA) demonstrou adicionar acurácia às avaliações de estado nutricional e de volume em pacientes em diálise (HD). Objetivo: descrever amostra de pacientes em diálise de um único centro quanto aos aspectos demográficos e BIA na distribuição de volume e no estado nutricional, e a mortalidade em 12 meses de acompanhamento. Métodos: estudo de coorte observacional prospectivo para avaliar pacientes prevalentes em HD com BIA de frequência única. Resultados: avaliamos 82 pacientes, 29% acima de 65 anos. Pacientes idosos apresentaram maior AEC/ACT (0,51 vs. 0,44; p < 0,0001), e ângulo de fase mais estreito (PhA) (4,9 vs. 6,4º; p < 0,0001). Quinze pacientes (18,2%) foram a óbito durante acompanhamento, oito (53%) eram idosos. Óbito foi associado à idade (62,6 vs. 50,2 anos, p = 0,012), PhA pós-HD (4,8 vs. 6,2º; p = 0,0001), e AEC/ACT pós-HD (0,50 vs. 0,45, p = 0,015). A análise da curva ROC para prever mortalidade constatou que AEC/ACT ≥ 0,47 e PhA ≤ 5,5º apresentam melhor sensibilidade e especificidade. Sobrevida do paciente em um ano foi menor com AEC/ACT pós-HD ≥ 0,47 (69,5% vs. 90,6%; p = 0,019), idade ≥ 65 anos (64,2% vs. 86,2%; p = 0,029), e PhA ≤ 5,5º (68,2 vs. 91,0%; p = 0,002). A análise de regressão de Cox demonstrou que PhA [HR 5,04 (IC 95% 1,60-15,86); p = 0,006] permaneceu associado ao óbito após ajuste para idade e AEC/ACT. Conclusão: BIA é útil ao avaliar distribuição de volume e nutrição em pacientes em HD, e juntamente com julgamento clínico, pode ajudar a determinar o peso seco, principalmente em pacientes idosos. PhA mais estreito e maior AEC/ACT pós-HD foram associados a pior sobrevida em um ano.

Bioimpedanciometry in nutritional and hydration assessments in a single dialysis center.

BACKGROUND: Bioimpedance analysis (BIA) has been demonstrated to add accuracy to nutritional and volume status assessments in dialysis (HD) patients. AIM: to describe a sample of dialysis patients from a single center on their demographics and BIA of volume distribution and nutritional status, and mortality during 12-month follow-up. METHODS: prospective observational cohort study to evaluate vintage HD patients with single-frequency BIA. RESULTS: we evaluated 82 patients, 29% over 65 years old. Elderly patients had higher ECW/TBW (0.51 vs. 0.44, p < 0.0001), and narrower phase angle (PhA) (4.9 vs. 6.4º, p < 0.0001). Fifteen patients (18.2%) died during follow-up, eight (53%) were elderly. Death was associated with age (62.6 vs. 50.2 years, p = 0.012), post-HD PhA (4.8 vs. 6.2º, p = 0.0001), and post-HD ECW/TBW (0.50 vs. 0.45, p = 0.015). The ROC curve analysis to predict mortality found ECW/TBW ≥ 0.47 and PhA ≤ 5.5º to have the best sensitivity and specificity. One-year patient survival was lower with post-HD ECW/TBW ≥ 0.47 (69.5% vs. 90.6%, p = 0.019), age ≥ 65 years (64.2%, vs. 86.2%, p = 0.029), and PhA ≤ 5.5º (68.2 vs. 91.0%, p = 0.002). Cox regression analysis demonstrated that PhA [HR 5.04 (95%CI 1.60-15.86), p = 0.006] remained associated with death after adjusting for age and ECW/TBW. CONCLUSION: BIA is useful in assessing volume distribution and nutrition in HD patients, and combined with clinical judgement, may help determine dry weight, especially in elderly patients. Narrower PhA and higher ECW/TBW after HD were associated with poorer one-year survival.

Real-world effectiveness and safety of direct-acting antivirals for the treatment of hepatitis C virus in kidney and liver transplant recipients: experience of a large transplant center in Brazil

ABSTRACT Direct-acting antivirals are the gold-standard treatment for chronic HCV infections, but few studies have investigated their use on kidney and liver transplant recipients. We conducted a real-world study to evaluate the rates of sustained virological response with direct-acting antivirals in kidney and liver transplant recipients. Moreover, it also aimed to evaluate direct-acting antivirals (DAAs) interference with immunosuppressant levels and to describe the frequency of adverse events. As part of this retrospective observational cohort, we included adult patients that had undergone a kidney transplant (KT) or liver transplant (LT) at our center, had a chronic HCV infection, and were treated with DAAs from June 2016 to December 2021. A total of 165 patients were included in the analysis, divided in 108 KT and 57 LT recipients. HCV genotype 1 was more frequent in KT (58.4%), and genotype 3 was more prevalent in LT (57.9%) patients. Sustained virological response was achieved in 89.6% of patients. Adverse effects were reported by 36% of patients. There were significant interactions with immunosuppressants requiring dose adjustments. A total of three episodes of rejection were reported in KT recipients. In conclusion, DAA treatment resulted in high rates of SVR and was well tolerated in both kidney and liver transplant patients. Adverse events were frequent but not severe in most patients, with low treatment drop-out rates. Interactions with immunosuppressants need monitoring since dose adjustments may be required. Reporting real-life experiences is important to help build evidence for patient management in non-controlled environments.

Latent tuberculosis screening before kidney transplantation in the South of Brazil / Rastreamento de tuberculose latente antes do transplante renal no Sul do Brasil

Abstract Background: Tuberculosis (TB) is a prevalent infection after kidney transplantation (KT) in high-burden countries. Latent tuberculosis infection (LTBI) screening includes previous TB history, chest radiograph findings, and tuberculin test (TST) and/or interferon-gamma release assays (IGRAs) results. We aimed to compare our routine LTBI screening of KT candidates and living donors (LD) with their IGRA results, and evaluate if this would improve isoniazid (INH) treatment referral. Methods: We evaluated adult KT candidates and LD with complete routine LTBI screening and QuantiFERON-TB® Gold In-Tube (QFT) testing. Blood samples were collected from April 4th, 2014 to October 31st, 2018, with follow-up until October 31st, 2019. Results: There were 116 KT recipients, with 30% QFT-positive results. Positive QFT was associated with past TB history (p=0.007), positive TST (p<0.0001), residual radiographic lesions (p=0.003), and diabetes (p=0.035). There were 25 LD, 40% had positive QFT. Positive QFT was associated with a positive TST (p=0.002). Positive QFT results increased INH referral in 80%. Post-transplant TB incidence was 2.6% in a median follow-up of 2 (1-33) months. No variables were associated with post-transplant TB. TB patients had inferior, although non-significant, 5-year graft survival (66.7% vs. 76.5%) (p = 0.402). Conclusion: In the present study, the association of QFT to our routine LTBI screening incremented INH treatment referral, but there was still a high incidence of post-transplant TB, possibly related to other forms of infection, such as new exposure and donor transmission.

Resumo Histórico: Tuberculose (TB) é uma infecção relativamente comum pós-transplante renal (TR) em países com alta prevalência da doença. O rastreamento de infecção latente por tuberculose (ILTB) inclui histórico prévio de TB, achados de radiografia do tórax, resultados do teste tuberculínico (TT) e/ou de ensaio de liberação de interferon-gama (IGRAs). Nosso objetivo foi comparar nossa avaliação de rotina de candidatos ao TR e doadores vivos (DV) com seus resultados de IGRA, avaliando se aumentaria o encaminhamento para tratamento com isoniazida (INH). Métodos: Avaliamos candidatos adultos ao TR e DV com rastreamento para ILTB de rotina completo e coleta de testes QuantiFERON-TB® Gold In-Tube (QFT). Coletamos amostras sanguíneas de 4 de Abril, 2014 - 31 de Outubro, 2018, com acompanhamento até 31 de Outubro, 2019. Resultados: Avaliamos 116 receptores de TR, 30% sendo QFT-positivo. QFT positivo foi associado ao histórico prévio de TB (p=0,007), TT positivo (p<0,0001), lesões radiográficas residuais (p=0,003), diabetes (p=0,035). Avaliamos 25 DV, 40% apresentaram QFT positivo. QFT positivo foi associado a TT positivo (p=0,002). Resultados positivos do QFT aumentaram o encaminhamento para INH em 80%. A incidência de TB pós-transplante foi 2,6% em uma mediana de acompanhamento de 2 (1-33) meses. Nenhuma variável foi associada à TB pós-transplante. Pacientes com TB tiveram sobrevida do enxerto em 5 anos inferior, embora não-significativa (66,7% vs. 76,5%) (p = 0,402). Conclusão: Neste estudo, a associação do QFT à nossa avaliação de ILTB de rotina aumentou o encaminhamento para tratamento com INH, mas ainda houve alta incidência de TB pós-transplante, possivelmente relacionada a outras formas de infecção, como nova exposição e transmissão pelos doadores.

Phasing out the pre-transplant cytotoxicity crossmatch: Are we missing something? / Exclusão da prova cruzada por citotoxicidade pré-transplante: estamos perdendo algo

Abstract Introduction: The anti-human globulin-enhanced complement-dependent cytotoxicity crossmatch (AHG-CDCXM) assay has been used to assess the presence of donor-specific antibodies (DSA) in recipient's serum before kidney transplantation. The flow cytometric crossmatch (FCXM) assay was first introduced as an additional test. The aim of this study was to clinically validate the single use of the FCXM assay. Methods: This study compared the outcomes of a cohort of kidney transplant patients that underwent FCXM only (FCXM group) versus a cohort of kidney transplant patients that underwent AHG-CDCXM (control group). Results: Ninety-seven patients in the FCXM group and 98 controls were included. All crossmatches in the control group were negative. One patient in the FCXM group had a positive B cell crossmatch. One year after transplantation, there were no significant differences in patient survival (p = 0.591) and graft survival (p = 0.692) between the groups. Also, no significant difference was found in the incidence of Banff ≥ 1A acute cellular rejection episodes (p = 0.289). However, acute antibody-mediated rejections occurred in 3 controls (p = 0.028). Conclusion: The results showed that discontinuing the AHG-CDCXM assay does not modify the clinical outcomes in a 1-year follow-up.

Resumo Introdução: O ensaio de prova cruzada por citotoxicidade dependente do complemento antiglobulina humana (AHG-CDCXM - do inglês anti-human globulin-enhanced complement-dependent cytotoxicity crossmatch) tem sido usado para avaliar a presença de anticorpos específicos contra o doador (DSA - do inglês donor-specific antibodies) no soro do receptor antes do transplante renal. O ensaio de prova cruzada por citometria de fluxo (CFXM) foi introduzido pela primeira vez como um teste adicional. O objetivo deste estudo foi validar clinicamente o uso único do ensaio CFXM. Métodos: Este estudo comparou os resultados de uma coorte de pacientes de transplante renal que foram submetidos apenas ao CFXM (grupo CFXM) contra uma coorte de pacientes de transplante renal submetidos ao AHG-CDCXM (grupo controle). Resultados: Foram incluídos noventa e sete pacientes no grupo CFXM e 98 controles. Todas as provas cruzadas no grupo controle foram negativas. Um paciente no grupo CFXM teve uma prova cruzada positiva para células B. Um ano após o transplante, não houve diferenças significativas na sobrevida do paciente (p = 0,591) e na sobrevida do enxerto (p = 0,692) entre os grupos. Também não foi encontrada diferença significativa na incidência de episódios de rejeição aguda celular (p = 0,289) segundo critério de Banff ≥ 1A. No entanto, rejeições agudas mediadas por anticorpos ocorreram em 3 controles (p = 0,028). Conclusão: Os resultados mostraram que a interrupção do ensaio AHG-CDCXM não modifica os desfechos clínicos em um acompanhamento de 1 ano.

Latent tuberculosis screening before kidney transplantation in the South of Brazil.

BACKGROUND: Tuberculosis (TB) is a prevalent infection after kidney transplantation (KT) in high-burden countries. Latent tuberculosis infection (LTBI) screening includes previous TB history, chest radiograph findings, and tuberculin test (TST) and/or interferon-gamma release assays (IGRAs) results. We aimed to compare our routine LTBI screening of KT candidates and living donors (LD) with their IGRA results, and evaluate if this would improve isoniazid (INH) treatment referral. METHODS: We evaluated adult KT candidates and LD with complete routine LTBI screening and QuantiFERON-TB® Gold In-Tube (QFT) testing. Blood samples were collected from April 4th, 2014 to October 31st, 2018, with follow-up until October 31st, 2019. RESULTS: There were 116 KT recipients, with 30% QFT-positive results. Positive QFT was associated with past TB history (p=0.007), positive TST (p<0.0001), residual radiographic lesions (p=0.003), and diabetes (p=0.035). There were 25 LD, 40% had positive QFT. Positive QFT was associated with a positive TST (p=0.002). Positive QFT results increased INH referral in 80%. Post-transplant TB incidence was 2.6% in a median follow-up of 2 (1-33) months. No variables were associated with post-transplant TB. TB patients had inferior, although non-significant, 5-year graft survival (66.7% vs. 76.5%) (p = 0.402). CONCLUSION: In the present study, the association of QFT to our routine LTBI screening incremented INH treatment referral, but there was still a high incidence of post-transplant TB, possibly related to other forms of infection, such as new exposure and donor transmission.

Phasing out the pre-transplant cytotoxicity crossmatch: Are we missing something?

INTRODUCTION: The anti-human globulin-enhanced complement-dependent cytotoxicity crossmatch (AHG-CDCXM) assay has been used to assess the presence of donor-specific antibodies (DSA) in recipient's serum before kidney transplantation. The flow cytometric crossmatch (FCXM) assay was first introduced as an additional test. The aim of this study was to clinically validate the single use of the FCXM assay. METHODS: This study compared the outcomes of a cohort of kidney transplant patients that underwent FCXM only (FCXM group) versus a cohort of kidney transplant patients that underwent AHG-CDCXM (control group). RESULTS: Ninety-seven patients in the FCXM group and 98 controls were included. All crossmatches in the control group were negative. One patient in the FCXM group had a positive B cell crossmatch. One year after transplantation, there were no significant differences in patient survival (p = 0.591) and graft survival (p = 0.692) between the groups. Also, no significant difference was found in the incidence of Banff ≥ 1A acute cellular rejection episodes (p = 0.289). However, acute antibody-mediated rejections occurred in 3 controls (p = 0.028). CONCLUSION: The results showed that discontinuing the AHG-CDCXM assay does not modify the clinical outcomes in a 1-year follow-up.

Exploring the causes of the high incidence of delayed graft function after kidney transplantation in Brazil: a multicenter study.

This retrospective multicenter (n = 18) cohort study evaluated the incidence, risk factors, and the impact of delayed graft function (DGF) on 1-year kidney transplant (KT) outcomes. Of 3992 deceased donor KT performed in 2014-2015, the incidence of DGF was 54%, ranging from 29.9% to 87.7% among centers. Risk factors (lower-bound-95%CI OR upper-bound-95%CI ) were male gender (1.066 1.2491.463 ), diabetic kidney disease (1.053 1.2961.595 ), time on dialysis (1.005 1.0071.009 ), retransplantation (1.035 1.3971.885 ), preformed anti-HLA antibodies (1.011 1.3831.892 ), HLA mismatches (1.006 1.0661.130 ), donor age (1.011 1.0171.023 ), donor final serum creatinine (sCr) (1.239 1.3171.399 ), cold ischemia time (CIT) (1.031 1.0431.056 ), machine perfusion (0.401 0.5420.733 ), and induction therapy with rabbit antithymocyte globulin (rATG) (0.658 0.8000.973 ). Duration of DGF > 4 days was associated with inferior renal function and DGF > 14 days with the higher incidences of acute rejection, graft loss, and death. In conclusion, the incidence and duration of DGF were high and associated with inferior graft outcomes. While late referral and poor donor maintenance account for the high overall incidence of DGF, variability in donor and recipient selection, organ preservation method, and type of induction agent may account for the wide variation observed among transplant centers.

Prevalence of the NPHS2 variants p.R229Q, p.A242V, and p.R138Q in patients with focal segmental glomerulosclerosis.

BACKGROUND: NPHS2 gene variants are associated with focal segmental glomerulosclerosis (FSGS) and steroid-resistant nephrotic syndrome (SRNS). In this study, the prevalence of NPHS2 variants p.R229Q, p.A242V, and p.R138Q was investigated in patients with familial or sporadic FSGS. MATERIALS AND METHODS: The sample consisted of 40 children and 70 adults diagnosed with FSGS confirmed by renal biopsy. Clinical and laboratory parameters were evaluated. Genotyping for the three single nucleotide polymorphisms (SNPs) was performed by real-time polymerase chain reaction: two variants in exon 5 (p.R229Q and p.A242V) and one in exon 3 (p.R138Q). Variants were correlated with ethnicity, clinical presentation, treatment response, and renal outcomes. RESULTS: Among the 40 children analyzed, 20% had familial and 80% sporadic FSGS and among adults, 4.3% had familial and 95.7% sporadic FSGS, respectively. Overall, SRNS was found in 70% of adults and 90% in children. Among children, variants were detected in 2 (5%) with sporadic FSGS, p.R229Q and p.A242V in 1 each. Among adults, variants were present in 9 (12.9%) patients, all with sporadic FSGS, p.R229Q in 4 and p.A242V in 5. No patient had the p.R138Q variant. Among adults, a trend of higher proteinuria at the end of follow-up (p = 0.06) was found in patients carrying a variant. There was no significant association between NPHS2 variants with the clinical presentation, dependence on immunosuppressive treatment, or renal outcomes. Regarding ethnicity, all patients carrying the p.R229Q variant were White, while 67% of carriers of the p.A242V variant were Black. CONCLUSION: In these patients with familial or sporadic FSGS, the prevalence of p.R229Q and p.A242V variants in children was 5% and in adults 12.9%. More studies of patients with FSGS could better define a strategy for genetic analysis and therapeutic management.

Usefulness of Kidney Donor Profile Index (KDPI) to predict graft survival in a South Brazilian Cohort / Utilidade do Índice de Perfil de Doadores de Rins (KDPI) para prever a sobrevida do enxerto em uma coorte do Sul do Brasil

Abstract Introduction: Kidney Donor Profile Index (KDPI) has been incorporated in the United States to improve the kidney transplant allocation system. Objectives: To evaluate deceased kidney donors' profile using KDPI and compare to the previous United Network for Organ Sharing (UNOS) definition of expanded criteria donors (ECD) and assess the KDPI applicability to predict five-year graft survival and renal function in our sample. Methods: Retrospective cohort of 589 kidney transplants from deceased donors performed from January 2009 to May 2013 with follow-up until May 2018. Results: In 589 kidney transplants, 36.6% of donors were classified as ECD and 28.8% had KDPI ≥ 85%. Mean KDPI was 63.1 (95%CI: 60.8-65.3). There was an overlap of standard and ECD in KDPI between 60 and 95 and a significantly lower death-censored graft survival in KDPI ≥ 85% (78.6%); KDPI 0-20: 89.8%, KDPI 21-59: 91.6%, and KDPI 60-84: 83.0%; p = 0.006. The AUC-ROC was 0.577 (95%CI: 0.514-0.641; p = 0.027). Renal function at 5 years was significantly lower according to the incremental KDPI (p < 0.002). KDPI (HR 1.011; 95%CI 1.001-1.020; p = 0.008), donor-specific antibodies (HR 2.77; 95%CI 1.69-4.54; p < 0.001), acute rejection episode (HR 1.73; 95%CI 1.04-2.86; p = 0.034) were independent and significant risk factors for death-censored graft loss at 5 years. Conclusion: In our study, 36.6% were classified as ECD and 28.8% had KDPI ≥ 85%. KDPI score showed a moderate power to predict graft survival at 5 years. Renal function was significantly lower in patients with higher KDPI.

Resumo Introdução: O Índice de Perfil de Doadores de Rins (KDPI) foi adotado nos Estados Unidos para melhorar o sistema de alocação de transplantes renais. Objetivos: avaliar o perfil dos doadores de rim falecidos usando o KDPI e comparar com a definição anterior do United Network for Organ Sharing (UNOS) de doadores de critérios expandidos (DCE) e avaliar a aplicabilidade do KDPI para prever a sobrevida do enxerto em cinco anos e a função renal em nossa amostra. Métodos: Coorte retrospectiva de 589 transplantes renais de doadores falecidos, realizada de janeiro de 2009 a maio de 2013, com acompanhamento até maio de 2018. Resultados: Em 589 transplantes renais, 36,6% dos doadores foram classificados como DCE e 28,8% apresentaram KDPI ≥ 85%. O KDPI médio foi de 63,1 (IC 95%: 60,8-65,3). Houve uma sobreposição de padrão e DCE no KDPI entre 60 e 95 e uma sobrevida do enxerto censurada por óbito significativamente menor no KDPI ≥ 85% (78,6%); KDPI 0-20: 89,8%, KDPI 21-59: 91,6% e KDPI 60-84: 83,0%; p = 0,006. A ASC-ROC foi de 0,577 (IC 95%: 0,514-0,641; p = 0,027). A função renal aos 5 anos foi significativamente menor de acordo com o aumento do KDPI (p <0,002). KDPI (HR 1.011; 95% CI 1.001-1.020; p = 0.008), anticorpos específicos contra doadores (HR 2,77; 95% CI 1,69-4,54; p <0,001), episódio de rejeição aguda (HR 1,73; 95% CI 1,04-2,86; p = 0,034) foram fatores de risco independentes e significativos para perda do enxerto censurada por óbito em 5 anos. Conclusão: Em nosso estudo, 36,6% foram classificados como DCE e 28,8% apresentaram KDPI ≥ 85%. O escore KDPI mostrou potencial moderado para prever a sobrevida do enxerto em 5 anos. A função renal foi significativamente menor nos pacientes com maior KDPI.

Usefulness of Kidney Donor Profile Index (KDPI) to predict graft survival in a South Brazilian Cohort.

INTRODUCTION: Kidney Donor Profile Index (KDPI) has been incorporated in the United States to improve the kidney transplant allocation system. OBJECTIVES: To evaluate deceased kidney donors' profile using KDPI and compare to the previous United Network for Organ Sharing (UNOS) definition of expanded criteria donors (ECD) and assess the KDPI applicability to predict five-year graft survival and renal function in our sample. METHODS: Retrospective cohort of 589 kidney transplants from deceased donors performed from January 2009 to May 2013 with follow-up until May 2018. RESULTS: In 589 kidney transplants, 36.6% of donors were classified as ECD and 28.8% had KDPI ≥ 85%. Mean KDPI was 63.1 (95%CI: 60.8-65.3). There was an overlap of standard and ECD in KDPI between 60 and 95 and a significantly lower death-censored graft survival in KDPI ≥ 85% (78.6%); KDPI 0-20: 89.8%, KDPI 21-59: 91.6%, and KDPI 60-84: 83.0%; p = 0.006. The AUC-ROC was 0.577 (95%CI: 0.514-0.641; p = 0.027). Renal function at 5 years was significantly lower according to the incremental KDPI (p < 0.002). KDPI (HR 1.011; 95%CI 1.001-1.020; p = 0.008), donor-specific antibodies (HR 2.77; 95%CI 1.69-4.54; p < 0.001), acute rejection episode (HR 1.73; 95%CI 1.04-2.86; p = 0.034) were independent and significant risk factors for death-censored graft loss at 5 years. CONCLUSION: In our study, 36.6% were classified as ECD and 28.8% had KDPI ≥ 85%. KDPI score showed a moderate power to predict graft survival at 5 years. Renal function was significantly lower in patients with higher KDPI.