High versus low mean arterial pressure target in liver transplant patients. An open, controlled, single-center, randomized clinical trial - Protocol and methods (LIVER-PAM).

OBJECTIVE: To explain the rationale and protocol of the methods and analyses to be used in the LIVER-PAM randomized clinical trial, which seeks to understand whether a higher mean arterial pressure is capable of reducing the incidence of renal dysfunction postoperatively after liver transplantation. METHODS: LIVER-PAM is an open-label, randomized, controlled, singlecenter clinical trial. Patients randomized to the intervention group will have a mean arterial pressure of 85 - 90mmHg in the initial 24 hours of postoperative management, while patients in the control group will have a mean arterial pressure of 65 - 70mmHg in the same period. A sample of 174 patients will be required to demonstrate a 20% reduction in the absolute incidence of renal dysfunction, with a power of 80% and an alpha of 0.05. CONCLUSION: If a 20% reduction in the absolute incidence of renal dysfunction in the postoperative period of liver transplantation is achieved with higher target mean arterial pressure in the first 24 hours, this would represent an inexpensive and simple therapy for improving current outcomes in the management of liver transplant patients.ClinicalTrials.gov Registry: NCT05068713.

High versus low mean arterial pressure target in liver transplant patients. An open, controlled, single-center, randomized clinical trial - Protocol and methods (LIVER-PAM) / Alto versus baixo alvo de pressão arterial média em pacientes submetidos a transplante hepático. Um estudo clínico aberto, controlado, unicêntrico e randomizado -Protocolo e métodos (LIVER-PAM)

ABSTRACT Objective: To explain the rationale and protocol of the methods and analyses to be used in the LIVER-PAM randomized clinical trial, which seeks to understand whether a higher mean arterial pressure is capable of reducing the incidence of renal dysfunction postoperatively after liver transplantation. Methods: LIVER-PAM is an open-label, randomized, controlled, singlecenter clinical trial. Patients randomized to the intervention group will have a mean arterial pressure of 85 - 90mmHg in the initial 24 hours of postoperative management, while patients in the control group will have a mean arterial pressure of 65 - 70mmHg in the same period. A sample of 174 patients will be required to demonstrate a 20% reduction in the absolute incidence of renal dysfunction, with a power of 80% and an alpha of 0.05. Conclusion: If a 20% reduction in the absolute incidence of renal dysfunction in the postoperative period of liver transplantation is achieved with higher target mean arterial pressure in the first 24 hours, this would represent an inexpensive and simple therapy for improving current outcomes in the management of liver transplant patients. ClinicalTrials.gov Registry:NCT05068713

RESUMO Objetivo: Explicitar o racional e o protocolo de métodos e análises a serem utilizadas no ensaio clínico randomizado LIVER-PAM, que busca entender se um nível mais alto de pressão arterial média é capaz de reduzir a incidência de disfunção renal no pós-operatório de transplante hepático. Métodos: O LIVER-PAM é um estudo clínico randomizado, controlado, unicêntrico e aberto. Pacientes randomizados para o grupo intervenção terão como alvo de pressão arterial média 85 - 90mmHg nas 24 horas iniciais do manejo pós-operatório, enquanto pacientes do grupo controle terão como alvo de pressão arterial média 65 - 70mmHg no mesmo período. Uma amostra de 174 pacientes será necessária para demonstrar redução de 20% na incidência absoluta de disfunção renal, com poder de 80% e alfa de 0,05. Conclusão: Se a redução de 20% da incidência absoluta de disfunção renal no pós-operatório de transplante hepático for obtida com alvos maiores de pressão arterial média nas primeiras 24 horas, o manejo do paciente nesse cenário encontraria uma terapia barata e simples para a melhoria dos desfechos atuais. Registro Cliniclatrials.gov:NCT05068713

Acute kidney injury and renal replacement therapy: terminology standardization / Injúria renal aguda e métodos de suporte: padronização da nomenclatura

Abstract The Department of Acute Kidney Injury (IRA) of the Brazilian Society of Nephrology prepared this document for the purpose of standardizing AKI terminology and dialysis modalities in the Portuguese language for Brazil. Several terms with similar meanings have been used in AKI and its dialysis modalities, causing confusion and disparities among patients, nephrologists, health institutions, private care companies, insurance companies and government entities. These disparities can impact medical care, hospital organization and care, as well as the funding and reimbursement of AKI-related procedures. Thus, consensual nomenclature and definitions were developed, including the definitions of AKI, acute kidney disease (AKD) and chronic kidney disease (CKD). Additionally, we addressed all dialysis modalities and extracorporeal procedures related to AKI, currently approved and available in the country. The Brazilian Society of Nephrology hopes that this Consensus can standardize the terminology and provide technical support to all involved in AKI care in Brazil.

Resumo O Departamento de Injúria Renal Aguda (IRA) da Sociedade Brasileira de Nefrologia elaborou o presente documento para fins de padronização da terminologia em IRA e modalidades dialíticas na língua portuguesa para o Brasil. Diversos termos com significados semelhantes têm sido empregados em IRA e suas modalidades dialíticas, causando confusão e disparidades entre pacientes, nefrologistas, instituições de saúde, empresas privadas de assistência, seguradoras e entidades governamentais. Essas disparidades podem impactar a assistência médica, a organização e o atendimento hospitalares, assim como o financiamento e reembolso dos procedimentos relacionados com a IRA. Assim, nomenclatura e definições consensuais foram elaboradas, incluindo-se as definições de IRA, doença renal aguda (DRA) e doença renal crônica (DRC). Adicionalmente, todas as modalidades dialíticas e os procedimentos extracorpóreos relacionados a IRA, atualmente aprovados e disponíveis no país, foram abordados. A Sociedade Brasileira de Nefrologia espera que este Consenso possa padronizar a nomenclatura e prover suporte técnico para todos os atores envolvidos na assistência à IRA no Brasil.

Acute kidney injury and renal replacement therapy: terminology standardization.

The Department of Acute Kidney Injury (IRA) of the Brazilian Society of Nephrology prepared this document for the purpose of standardizing AKI terminology and dialysis modalities in the Portuguese language for Brazil. Several terms with similar meanings have been used in AKI and its dialysis modalities, causing confusion and disparities among patients, nephrologists, health institutions, private care companies, insurance companies and government entities. These disparities can impact medical care, hospital organization and care, as well as the funding and reimbursement of AKI-related procedures. Thus, consensual nomenclature and definitions were developed, including the definitions of AKI, acute kidney disease (AKD) and chronic kidney disease (CKD). Additionally, we addressed all dialysis modalities and extracorporeal procedures related to AKI, currently approved and available in the country. The Brazilian Society of Nephrology hopes that this Consensus can standardize the terminology and provide technical support to all involved in AKI care in Brazil.

Reduced hippocampal manganese-enhanced MRI (MEMRI) signal during pilocarpine-induced status epilepticus: edema or apoptosis?

Manganese-enhanced MRI (MEMRI) has been considered a surrogate marker of Ca(+2) influx into activated cells and tracer of neuronal active circuits. However, the induction of status epilepticus (SE) by kainic acid does not result in hippocampal MEMRI hypersignal, in spite of its high cell activity. Similarly, short durations of status (5 or 15min) induced by pilocarpine did not alter the hippocampal MEMRI, while 30 min of SE even reduced MEMRI signal Thus, this study was designed to investigate possible explanations for the absence or decrease of MEMRI signal after short periods of SE. We analyzed hippocampal caspase-3 activation (to evaluate apoptosis), T2 relaxometry (tissue water content) and aquaporin 4 expression (water-channel protein) of rats subjected to short periods of pilocarpine-induced SE. For the time periods studied here, apoptotic cell death did not contribute to the decrease of the hippocampal MEMRI signal. However, T2 relaxation was higher in the group of animals subjected to 30min of SE than in the other SE or control groups. This result is consistent with higher AQP-4 expression during the same time period. Based on apoptosis and tissue water content analysis, the low hippocampal MEMRI signal 30min after SE can potentially be attributed to local edema rather than to cell death.

Avaliação da terapia com fluido no período perioperatório da ovariossalpingohisterectomia, em cadelas com piometra e insuficiência renal aguda / Avaliation of perioperative conservative treatment in pyometra ovariohysterectomy bitches of in acute renal failure

A insuficiência renal aguda foi avaliada em 351 cadelas com piometra, selecionando-se 132 pelos critérios: creatinina > 2,4 mg/dL e/ou ureia > 80 mg/dL e/ou aumentos relativos de 100% de creatinina e/ou ureia séricas, no diagnóstico, 24 horas após a ovariossalpingohisterectomia e na retirada dos pontos. Foi administrado Ringer lactato de sódio até 90 mL/kg/h, durante quatro horas, ou três dias. Os parâmetros avaliados antes e após cada terapia foram: peso, pressão arterial sistólica (PAS), frequência cardíaca, função renal, hemogasimetria arterial, bioquímica sérica e urinária, unidade de remoção de ureia, fração de excreção de eletrólitos e clearance de creatinina. A análise univariada detectou diferença significante (p < 0,05) para: PAS, pH urinário, peso corpóreo, ureia e creatinina séricas, fração de excreção de eletrólitos e clearance da creatinina. Comparadas as sobreviventes (79,6%) com as não sobreviventes (20,4%), respectivamente, detectou-se creatinina sérica de 2,38 ± 1,33 mg/dL (média ± desvio padrão) e mediana 2,2 mg/dL e de 5,54 ± 3,0 mg/dL (média ± desvio padrão) e mediana 4,4 mg/dl, com diferença significante (p < 0,0001). Quanto ao clearance da creatinina endógena nas sobreviventes, 1,82 ± 1,74 mL/kg/min (média ± desvio padrão) e mediana 1,34 mg/dL e as não sobreviventes 0,36 ± 0,38 mg/dL (média ± desvio padrão) e mediana 0,23 mg/dL, com diferença significativa (p < 0,0001). Conclui-se que o critério de inclusão pode auxiliar na seleção dos animais em estado grave e o clearance da creatinina, considerado relevante quando observados valores > 1 mL/kg/min; negativo com valores < 1 mL/kg/min e indicador de falência renal grave e ou morte para valores < 0,5 ml/kg/min.

Acute renal failure (ARF) was evaluated prospectively in 351 female dogs with piometra, 132 animals were selected for this study, fulfilling the following criteria, measured in three moments (immediately after the diagnosis, 24 hours after the hysterectomy and when the suture was removed): creatinine > 2.4 mg/dL and/or urea > 80 mg/dL and/or relative increases of 100% in comparison with values previously obtained. The animals selected for the prospective study received conservative treatment consisting in lactated Ringer solution, with the maximum dose of 90 mL/kg/hr, during four hours. The factors evaluated before and after the therapy were: weight, systolic arterial pressure, heart rate, renal function, arterial hemogasometry, serum and urinary biochemistry and the endogenous renal creatinine clearance. The evaluated parameters showed significant statistical differences (p < 0.05) when companing: PAS (systolic arterial pressure), urinary pH, wheigt, serum urea and creatinine, excretion electrolyte rate and creatinine clearance. Howerer, the survining animals (79.6%) that received the treatment described above showed decresead levels of serum creatinine- 2,38 ± 1,33mg/dL and median 2.2 mg/dL – when compared to the non-survining animals (20.4%) that received the same treatment – 5.54 ± 3.0mg/dL and median 4.4mg/dL – (p < 0.0001). When comparing the endogenous creatinine clearance, the survining animals had higher values – 1.82 ± 1.74mL/kg/min and median 1.34 mL/kg/min – than the non-survining animals – 0.36 ± 0.38 mL/kg/min and median 0.23 mL/kg/min – (p < 0.0001). Concluding: the criteria used to include the animals in this study can help to select the severely affected animals. Values higher than 1mL/kg/min are considered as a good prognosis while values lower than 1mL/kg/min are considered as a restricted prognosis. Values lower than 0.5 mL/kg/min are considered as strong predictors of severe renal failure or death.