PCRRT Expert Committee ICONIC Position Paper on Prescribing Kidney Replacement Therapy in Critically Sick Children With Acute Liver Failure

Management of acute liver failure (ALF) and acute on chronic liver failure (ACLF) in the pediatric population can be challenging. Kidney manifestations of liver failure, such as hepatorenal syndrome (HRS) and acute kidney injury (AKI), are increasingly prevalent and may portend a poor prognosis. The overall incidence of AKI in children with ALF has not been well-established, partially due to the difficulty of precisely estimating kidney function in these patients. The true incidence of AKI in pediatric patients may still be underestimated due to decreased creatinine production in patients with advanced liver dysfunction and those with critical conditions including shock and cardiovascular compromise with poor kidney perfusion. Current treatment for kidney dysfunction secondary to liver failure include conservative management, intravenous fluids, and kidney replacement therapy (KRT). Despite the paucity of evidence-based recommendations concerning the application of KRT in children with kidney dysfunction in the setting of ALF, expert clinical opinions have been evaluated regarding the optimal modalities and timing of KRT, dialysis/replacement solutions, blood and dialysate flow rates and dialysis dose, and anticoagulation methods

Cardiorenal syndrome in the pediatric population: A systematic review

The concept of cardiorenal syndrome (CRS) is derived from the crosstalk between the heart and kidneys in pathological conditions. Despite the rising importance of CRS, there is a paucity of information on the understanding of its pathophysiology and management, increasing both morbidity and mortality for patients. This review summarizes the existing conceptual pathophysiology of different types of CRS and delves into the associated therapeutic modalities with a focus on pediatric cases. Prospective or retrospective observational studies, comparative studies, case reports, case–control, and cross-sectional studies that include pediatric patients with CRS were included in this review. Literature was searched using PubMed, EMBASE, and Google Scholar with keywords including “cardio-renal syndrome, type,” “reno-cardio syndrome,” “children,” “acute kidney injury,” and “acute decompensated heart failure” from January 2000 to January 2021. A total of 14 pediatric studies were ultimately included and analyzed, comprising a combined population of 3608 children of which 32% had CRS. Of the 14 studies, 57% were based on type 1 CRS, 14% on types 2 and 3 CRS, and 7% were on types 4 and 5 CRS. The majority of included studies were prospective cohort, although a wide spectrum was observed in terms of patient age, comorbidities, etiologies, and treatment strategies. Commonly observed comorbidities in CRS type 1 were hematologic, oncologic, cardiology-related side effects, muscular dystrophy, and pneumonia/bronchiolitis. CRS, particularly type 1, is prevalent in children and has a significant risk of mortality. The current treatment regimen primarily involves diuretics, extracorporeal fluid removal, and treatment of underlying etiologies and comorbidities

Oral famotidine versus placebo in non-hospitalised patients with COVID-19: a randomised, double-blind, data-intense, phase 2 clinical trial.

OBJECTIVE: We assessed whether famotidine improved inflammation and symptomatic recovery in outpatients with mild to moderate COVID-19. DESIGN: Randomised, double-blind, placebo-controlled, fully remote, phase 2 clinical trial (NCT04724720) enrolling symptomatic unvaccinated adult outpatients with confirmed COVID-19 between January 2021 and April 2021 from two US centres. Patients self-administered 80 mg famotidine (n=28) or placebo (n=27) orally three times a day for 14 consecutive days. Endpoints were time to (primary) or rate of (secondary) symptom resolution, and resolution of inflammation (exploratory). RESULTS: Of 55 patients in the intention-to-treat group (median age 35 years (IQR: 20); 35 women (64%); 18 African American (33%); 14 Hispanic (26%)), 52 (95%) completed the trial, submitting 1358 electronic symptom surveys. Time to symptom resolution was not statistically improved (p=0.4). Rate of symptom resolution was improved for patients taking famotidine (p<0.0001). Estimated 50% reduction of overall baseline symptom scores were achieved at 8.2 days (95% CI: 7 to 9.8 days) for famotidine and 11.4 days (95% CI: 10.3 to 12.6 days) for placebo treated patients. Differences were independent of patient sex, race or ethnicity. Five self-limiting adverse events occurred (famotidine, n=2 (40%); placebo, n=3 (60%)). On day 7, fewer patients on famotidine had detectable interferon alpha plasma levels (p=0.04). Plasma immunoglobulin type G levels to SARS-CoV-2 nucleocapsid core protein were similar between both arms. CONCLUSIONS: Famotidine was safe and well tolerated in outpatients with mild to moderate COVID-19. Famotidine led to earlier resolution of symptoms and inflammation without reducing anti-SARS-CoV-2 immunity. Additional randomised trials are required