Corrigendum: PCRRT Expert Committee ICONIC position paper on prescribing kidney replacement therapy in critically sick children with acute liver failure.

[This corrects the article DOI: 10.3389/fped.2021.833205.].

Impact of Antiretroviral Therapy on Kidney Disease in HIV Infected Individuals - A Qualitative Systematic Review.

Kidney disease is the fourth most common cause of non-AIDS-related mortality in people living with HIV. Combination antiretroviral therapy (cART) remains the cornerstone of treatment. However, little is known about the impact of cART on disease outcomes in patients with HIV-associated nephropathy (HIVAN) and HIV-immune complex kidney disease (HIVICK). This systematic review evaluates the impact of cART on progression to end-stage kidney disease (ESKD) and other outcomes in HIV-infected individuals. We conducted a literature search utilizing PubMed, and Cochrane database and 11 articles met inclusion criteria for analysis of which nine HIVAN studies showed decreased progression to ESKD or death for subjects when treated with cART versus those untreated. However, two studies showed no survival advantage with cART. Three HIVICK studies showed improvement in delaying ESKD in subjects on cART compared to untreated subjects. cART appeared to reduce the risk to ESKD or death in patients with both HIVAN and HIVICK.

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.

The Fanconi anemia pathway and Breast Cancer: A comprehensive review of clinical data.

The development of breast cancer depends on several risk factors, including environmental, lifestyle and genetic factors. Despite the evolution of DNA sequencing techniques and biomarker detection, the epidemiology and mechanisms of various breast cancer susceptibility genes have not been elucidated yet. Dysregulation of the DNA damage response causes genomic instability and increases the rate of mutagenesis and the risk of carcinogenesis. The Fanconi Anemia (FA) pathway is an important component of the DNA damage response and plays a critical role in the repair of DNA interstrand crosslinks and genomic stability. The FA pathway involves 22 recognized genes and specific mutations have been identified as the underlying defect in the majority of FA patients. A thorough understanding of the function and epidemiology of these genes in breast cancer is critical for the development and implementation of individualized therapies that target unique tumor profiles. Targeted therapies (PARP inhibitors) exploiting the FA pathway gene defects have been developed and have shown promising results. This narrative review summarizes the current literature on the involvement of FA genes in sporadic and familial breast cancer with a focus on clinical data derived from large cohorts.

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.

COVID-19 in an Asymptomatic Renal Transplant Recipient Employed in the Health Care Setting: A Case Report.

During the ongoing pandemic, there have been varying presentations of coronavirus disease 2019 (COVID-19) infection, with the concern that patients who are immunosuppressed (due to underlying medical conditions and/or therapies) are at higher risk of severe disease. We report the case of an elderly renal transplant recipient working in a long-term health care facility who was being monitored by weekly surveillance testing and tested positive for COVID-19 by polymerase chain reaction (PCR) testing, despite having no clinical symptoms. He recovered with supportive care, despite being on multiple long-term immunosuppressant drugs and having multiple comorbidities. Additionally, it was found that he did not mount an antibody response, when he tested negative by serologic testing. Through this case, we wish to highlight the unique clinical scenario of asymptomatic patients who may have an underwhelming immune response to COVID-19, but may nevertheless be an important source of dissemination. We further discuss the probable mechanism of such asymptomatic presentations in immunosuppressed patients, while reinforcing the importance of self-isolation of COVID-19 patients (particularly in asymptomatic health care workers).

Kidney involvement in multisystem inflammatory syndrome in children: a pediatric nephrologist's perspective.

The initial report of the multisystem inflammatory syndrome in children (MIS-C) was from the UK in April 2020; since then, cases have been reported worldwide. Renal involvement has been seen commonly, ranging from 10% to 46%. Kidney involvement following severe acute respiratory syndrome coronavirus 2 infection in children with MIS-C is more common than initially thought and is associated with higher morbidity and mortality. There are several reports of a direct viral tropism of coronavirus disease 2019 and MIS-C-associated renal damage. This study's objective was to systematically review the current understanding of kidney involvement in children suffering from MIS-C. Based on our systemic literature search, 19 studies have either partially or fully discussed kidney involvement in MIS-C patients. Furthermore, we discuss the multifactorial pathogenesis contributing to acute kidney injury (AKI) development in MIS-C. The current review gives a pediatric nephrologist's perspective of the renal involvement in MIS-C, the incidence of AKI, the pathophysiology of AKI in MIS-C and the proposed therapeutic regimens available, including the need for kidney replacement therapy for a child with AKI associated with MIS-C. As the disease is rapidly evolving, more detailed clinical prospective studies are required to understand MIS-C and its role in AKI better.

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.

Onco-hypertension: An Emerging Specialty.

Cancer is one of the leading causes of death worldwide. With the introduction of newer chemotherapeutic agents, targeted therapies, and immunotherapy, the prognosis and survival of patients with cancer has remarkably improved. As a result, patients are living longer and experiencing long-term cardiovascular complications. Hypertension is an important risk factor for cardiovascular diseases. Patients with malignancy have multiple etiologies of hypertension development, worsening, or association. This is because of the complex interplay between cancer type, chemotherapeutic agent, patient age, antihypertensive agent, and preexisting comorbidities in the etiology and pathogenesis of hypertension. Management of hypertension in patients with cancer requires accurate blood pressure measurement and considering factors such as adjuvant therapy and cancer-related pain. There are no set guidelines for management of hypertension in this unique cohort, and the therapy should be individualized based on the treatment guidelines for the general population. Onco-hypertension is an emerging subspeciality and entails a multidisciplinary approach between oncology, primary care physicians, nephrology, and cardiology.