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.

Urine microscopy as a biomarker of Acute Kidney Injury following cardiac surgery with cardiopulmonary bypass / Microscopia urinária como biomarcador de lesão renal aguda após cirurgia cardíaca com circulação extracorpórea

Abstract Introduction: Acute kidney injury (AKI) occurs in about 22% of the patients undergoing cardiac surgery and 2.3% requires renal replacement therapy (RRT). The current diagnostic criteria for AKI by increased serum creatinine levels have limitations and new biomarkers are being tested. Urine sediment may be considered a biomarker and it can help to differentiate pre-renal (functional) from renal (intrinsic) AKI. Aims: To investigate the microscopic urinalysis in the AKI diagnosis in patients undergoing cardiac surgery with cardiopulmonary bypass. Methods: One hundred and fourteen patients, mean age 62.3 years, 67.5 % male, with creatinine 0.91 mg/dL (SD 0.22) had a urine sample examined in the first 24 h after the surgery. We looked for renal tubular epithelial cells (RTEC) and granular casts (GC) and associated the results with AKI development as defined by KDIGO criteria. Results: Twenty three patients (20.17 %) developed AKI according to the serum creatinine criterion and 76 (66.67 %) by the urine output criterion. Four patients required RRT. Mortality was 3.51 %. The use of urine creatinine criterion to predict AKI showed a sensitivity of 34.78 % and specificity of 86.81 %, positive likelihood ratio of 2.64 and negative likelihood ratio of 0.75, AUC-ROC of 0.584 (95%CI: 0.445-0.723). For the urine output criterion sensitivity was 23.68 % and specificity 92.11 %, AUC-ROC was 0.573 (95%CI: 0.465-0.680). Conclusion: RTEC and GC in urine sample detected by microscopy is a highly specific biomarker for early AKI diagnosis after cardiac surgery.

Resumo Introdução: Lesão renal aguda (LRA) ocorre em cerca de 22% dos pacientes submetidos a cirurgia cardíaca e 2,3% necessitam de terapia renal substitutiva (TRS). Os atuais critérios diagnósticos para LRA fundamentados no aumento dos níveis de creatinina sérica apresentam limitações e novos biomarcadores estão sendo testados. O sedimento urinário é um biomarcador que pode ajudar a diferenciar a LRA pré-renal (funcional) da LRA renal (intrínseca). Objetivos: Investigar a urinálise microscópica no diagnóstico de LRA em pacientes submetidos a cirurgia cardíaca com circulação extracorpórea. Métodos: Um total de 114 pacientes com idade média de 62,3 anos, 67,5% do sexo masculino e níveis médios de creatinina de 0,91 mg/dL (DP 0,22) tiveram amostras de urina examinadas nas primeiras 24 horas após a cirurgia. A identificação de células epiteliais tubulares renais (CETR) e cilindros granulares (CG) foi associada a desfechos de desenvolvimento de LRA conforme os critérios do KDIGO. Resultados: Vinte e três pacientes (20,17%) desenvolveram LRA pelo critério de creatinina sérica e 76 (66,67%) pelo critério de diurese. Quatro pacientes necessitaram de TRS. A mortalidade foi de 3,51%. O uso da creatinina urinária como critério preditivo para LRA mostrou sensibilidade de 34,78% e especificidade de 86,81%; razão de verossimilhança positiva de 2,64 e razão de verossimilhança negativa de 0,75; e ASC-COR de 0,584 (IC 95%: 0,445-0,723). Para o critério de diurese, a sensibilidade foi de 23,68% e a especificidade 92,11%; a ASC-COR foi 0,573 (IC 95%: 0,465-0,680). Conclusão: A identificação de CETR e CG em amostras de urina por microscopia representa um biomarcador altamente específico para o diagnóstico precoce de LRA após cirurgia cardíaca.

Effect of conversion from calcineurin inhibitors to everolimus on hepatitis C viremia in adult kidney transplant recipients / Efeitos da conversão de inibidores da calcineurina para Everolimo na viremia por hepatite C em receptores adultos de transplantes renais

ABSTRACT Introduction: Currently, there is no specific immunosuppressive protocol for hepatitis C (HCV)-positive renal transplants recipients. Thus, the aim of this study was to evaluate the conversion effect to everolimus (EVR) on HCV in adult kidney recipients. Method: This is an exploratory single-center, prospective, randomized, open label controlled trial with renal allograft recipients with HCV-positive serology. Participants were randomized for conversion to EVR or maintenance of calcineurin inhibitors. Results: Thirty patients were randomized and 28 were followed-up for 12 months (conversion group, Group 1 =15 and control group, Group 2 =13). RT-PCR HCV levels reported in log values were comparable in both groups and among patients in the same group. The statistical analysis showed no interaction effect between time and group (p value G*M= 0.852), overtime intra-groups (p-value M=0.889) and between group (p-value G=0.286). Group 1 showed a higher incidence of dyslipidemia (p=0.03) and proteinuria events (p=0.01), while no difference was observed in the incidence of anemia (p=0.17), new onset of post-transplant diabetes mellitus (p=1.00) or urinary tract infection (p=0.60). The mean eGFR was similar in both groups. Conclusion: Our study did not show viral load decrease after conversion to EVR with maintenance of antiproliferative therapy.

RESUMO Introdução: Atualmente não há um protocolo imunossupressor específico para os receptores de transplantes renais portadores de hepatite C (HCV). Assim, o objetivo deste estudo foi avaliar o efeito da conversão a Everolimo (EVR) na HCV em receptores adultos de transplantes renais. Método: Trata-se de um estudo unicêntrico, prospectivo, randomizado, exploratório, controlado, aberto em receptores de aloenxertos renais com sorologia positiva para HCV. Os participantes foram randomizados para conversão a EVR ou manutenção dos inibidores da calcineurina. Resultados: Trinta pacientes foram randomizados e 28 foram acompanhados por um período de 12 meses (grupo de conversão, Grupo 1 = 15 e grupo controle, Grupo 2 =13). Níveis de RT-PCR HCV descritos em valores logarítmicos foram comparáveis entre os grupos e entre pacientes em um mesmo grupo. A análise estatística não mostrou efeitos de interação entre tempo e grupo (valor p G*M= 0,852), ao longo do tempo em cada grupo (valor p M=0,889) e entre grupos (valor p G=0,286). O Grupo 1 apresentou uma maior incidência de eventos de dislipidemia (p=0,03) e proteinúria (p=0,01); não houve diferença na incidência de anemia (p=0,17), diabetes mellitus de início pós-transplante (p=1,00) ou infecção do trato urinário (p=0,60). A TFGe média foi semelhante nos dois grupos. Conclusão: Nosso estudo não mostrou redução da carga viral após conversão a EVR com manutenção do tratamento antiproliferativo.