Risultati per: Nuovi farmaci per il danno renale acuto (Acute kidney injury – AKI)

There is a fundamental question in emergency medicine: Is high-flow nasal oxygen an appropriate alternative to noninvasive ventilation across varied presentations of acute respiratory failure? In this issue of JAMA, a multicenter, adaptive, randomized clinical trial, conducted by the RENOVATE Investigators and the BRICNet Authors, explored the noninferiority of high-flow nasal oxygen vs noninvasive ventilation in reducing endotracheal intubation or death within 7 days across 5 distinct acute respiratory failure patient groups, including a dedicated COVID-19 cohort.

Cancer patients treated with radiotherapy in the abdominal and pelvic cavity develop radiation-induced enteritis, a condition that impairs their quality of life. Radiation injury depletes proliferative intestinal stem cells (ISCs); in response to this, the epithelium activates a regenerative program that facilitates the healing of the intestine. However, the mechanisms that induce the activation of the intestinal regenerative program are poorly characterized.

This randomized clinical trial compares the use of high-flow nasal oxygen vs noninvasive ventilation on the rates of endotracheal intubation or death at 7 days across 5 patient groups with acute respiratory failure.

Annals of Internal Medicine, Ahead of Print.

Circulation, Volume 151, Issue 10, Page 716-732, March 11, 2025. Albuminuria—increased urine albumin excretion—is associated with cardiovascular mortality among patients with diabetes, hypertension, chronic kidney disease, or heart failure, as well as among adults with few cardiovascular risk factors. Many authors have hypothesized that albuminuria reflects widespread endothelial dysfunction, but additional work is needed to uncover whether albuminuria is directly pathologic or causative of cardiovascular disease. Urinary albumin-to-creatinine ratio is an attractive, unifying biomarker of cardiovascular, kidney, and metabolic conditions that may be useful for identifying and monitoring disease trajectory. However, albuminuria may develop through unique mechanisms across these distinct clinical phenotypes. This state-of-the-art review discusses the role of albuminuria in cardiovascular, kidney, and metabolic conditions; identifies potential pathways linking albuminuria to adverse outcomes; and provides practical approaches to screening and managing albuminuria for clinical cardiologists. Future research is needed to determine how broadly and how frequently to screen patients for albuminuria, whether it is cost-effective to treat low-grade albuminuria (10–30 mg/g), and how to equitably offer newer antiproteinuric therapies across the spectrum of cardiovascular-kidney-metabolic diseases.

Objectives
Older people with kidney failure often have a limited range of treatment options, with few being well enough to receive a transplant. Instead, they either start dialysis or have ‘conservative kidney management’ (CKM). CKM involves care that focuses on managing the symptoms of kidney failure and maintaining quality of life in the absence of dialysis. The relative ability of dialysis and CKM to make older people live longer and feel better is uncertain. This study aimed to describe how older patients understand and decide between dialysis and CKM, as evidence suggests they may not be fully supported to make informed decisions between these treatments.

Design
Qualitative study using semistructured interviews, analysed using inductive thematic analysis and constant comparative techniques.

Setting
Three UK specialist kidney units.

Participants
Adults with estimated glomerular filtration rate (eGFR)

Background
Up to 50% of kidney transplant patients are diagnosed with delayed graft function (DGF) following transplantation—the majority being linked to ischaemia reperfusion injury (IRI). DGF is traditionally defined as the requirement for dialysis during the first week after transplantation and is associated with inferior graft and patient outcomes. Local synthesis of complement components, largely by the renal tubule, plays a critical role in IRI. We have developed Mirococept, a membrane-targeted complement inhibitor, that can be administered to the donor kidney ex vivo prior to transplantation. After administration, Mirococept is retained in the donor organ, thereby minimising the risk of systemic side effects. We previously launched the EMPIRIKAL study aiming to evaluate the efficacy of Mirococept in reducing DGF in deceased-donor kidney transplantation (KT). The funding body recommended termination of the study to allow a dose-saturating study before the next stage of clinical evaluation. This was carried out in a porcine kidney model and led to a revised dosing regimen for EMPIRIKAL-2 (60–180 mg compared with 5–25 mg in the initial trial). The EMPIRIKAL-2 trial (REC 24/NE/0071) aims to identify the most safe and efficacious dose of Mirococept to reduce DGF rate in deceased-donor KT.

Methods and analysis
EMPIRIKAL-2 is a Phase IIa multicentre double-blind randomised controlled trial (RCT) with an initial safety run. Participants will be recruited from renal departments at National Health Service tertiary hospital sites in the UK. The purpose of the safety run is to assess the tolerance of each of the three proposed Mirococept doses (60, 120 or 180 mg), before the RCT begins. Three patients will be assigned to each treatment dose, starting from the lower dose. The safety run will be considered successful if at least one dose can be taken forward to the RCT for comparison to placebo.
If safety is met, 144 participants (36 per arm excluding drop-outs) will be randomised to all doses meeting the safety criteria or placebo on a 1:1:1:1 basis. The primary endpoint is DGF, defined as the requirement for dialysis during the first week after transplantation. Safety evaluation will include the monitoring of laboratory data and the recording of all adverse events. Immunosuppression therapy, antibiotic and antiviral prophylaxis will be administered as per local centre protocols. Enrolment in the RCT is anticipated to take approximately 12 months, and patients will be followed-up for 12 months.

Ethics and dissemination
The study has been approved by the Northeast – Newcastle and North Tyneside 2 Research Ethics Service Committee, REC reference 24/NE/0071. The results of the study will be reported and disseminated at international conferences and in peer-reviewed scientific journals. Once published, a lay summary of the results will be made available to participants who request this information.

Trial registration number
ISRCTN14279222. Registered on 4 July 2024.

Protocol version
2.0 dated 9 May 2024.

Objective
Air pollution is an emerging risk factor for chronic kidney disease (CKD) that is typically ignored in preventive interventions. This study investigated whether long-term exposure to ambient air pollution in communities near petrochemical industries in the Niger Delta was associated with CKD.

Design
A cross-sectional study with an embedded citizen science inquiry.

Settings
Four communities situated at varying distances from a petrochemical refinery in Niger Delta, Nigeria.

Participants
We obtained sociodemographic, behavioural, exposure history and clinical data from 1460 participants who have resided for at least 5 years in the four communities. A citizen science approach was used to monitor air pollutant concentrations with eight community volunteers.

Results
The mean PM2.5, PM10 and volatile organic compounds (VOC) concentrations exceeded the WHO-acceptable limits in all four communities. CO2 was acceptable in the farthest communities from the refinery, while O3 was within acceptable limits in all communities. The total hazard quotient was relatively higher in the two communities near the refinery (11.27, 11.63) than those farther (9.63, 10.68), F=0.038, p=0.989. The overall prevalence of CKD was 12.3%; it was 17.9% in the community closest to the refinery and 8.0% in the farthest (2=18.292, p=0.004). Increasing age was the only independent risk factor for CKD after adjusting for confounding factors and intrahousehold design effect (adjusted OR 1.26; 95% CI 1.09 to 1.45, p=0.002).

Conclusion
Long-term exposure to ambient air pollution may increase CKD risk in susceptible populations. Social factors and environmental exposures associated with CKD are prevalent in the communities, necessitating multifaceted and inclusive approaches to mitigate air pollution and the associated kidney disease risks. More studies are required to explore the mechanism of air pollution-associated kidney disease and interventions to reverse or limit it.

Introduction
SARS-CoV-2 disease (COVID-19) has had an enormous health and economic impact globally. Although primarily a respiratory illness, multi-organ involvement is common in COVID-19, with evidence of vascular-mediated damage in the heart, liver, kidneys and brain in a substantial proportion of patients following moderate-to-severe infection. The pathophysiology and long-term clinical implications of multi-organ injury remain to be fully elucidated. Age, gender, ethnicity, frailty and deprivation are key determinants of infection severity, and both morbidity and mortality appear higher in patients with underlying comorbidities such as ischaemic heart disease, hypertension and diabetes. Our aim is to gain mechanistic insights into the pathophysiology of multiorgan dysfunction in people with COVID-19 and maximise the impact of national COVID-19 studies with a comparison group of COVID-negative controls.

Methods and analysis
COmorbidities and Sociodemographic factors on Multiorgan Injury following COVID-19 (COSMIC) is a prospective, multicentre UK study which will recruit 200 subjects without clinical evidence of prior COVID-19 and perform extensive phenotyping with multiorgan imaging, biobank serum storage, functional assessment and patient reported outcome measures, providing a robust control population to facilitate current work and serve as an invaluable bioresource for future observational studies.

Ethics and dissemination
Approved by the National Research Ethics Service Committee East Midlands (REC reference 19/EM/0295). Results will be disseminated via peer-reviewed journals and scientific meetings.

Trial registration number
COSMIC is registered as an extension of C-MORE (Capturing Multi-ORgan Effects of COVID-19) on ClinicalTrials.gov (NCT04510025).

Importance
Paediatric traumatic injury (PTI) is a leading cause of hospitalisation among children. Little is known about subsequent mental and physical health disorders while accounting for pre-injury health.

Objective
To compare pre-injury and post-injury mental and physical disorders in survivors of PTI with an uninjured matched cohort from the general population. This study hypothesised injured youth will have increased rates of mental and physical disorders relative to matched uninjured youth in the post-injury period.

Design
Retrospective longitudinal cohort study using linked administrative health data to examine paediatric patients hospitalised for injury between 1 January 2004 and 31 December 2016, measured 2 years pre-injury and 2 years post-injury.

Setting
Population-based study in Manitoba, Canada.

Participants
Youth

Introduction
Chronic kidney disease (CKD) causes significant morbidity and mortality. Medical therapies can reduce the progression of disease by up to 50%. CKD is undiagnosed in the majority of people who have it, resulting in undertreatment. CKD Stewardship (CKD-S) aims to identify hospital inpatients with undiagnosed mid-stage to late-stage CKD with the goal of facilitating diagnosis and initiating guideline-based therapies.

Methods and analysis
This prospective, multicentre, cohort study compares two models of care, CKD-S and standard care, for identification and management of CKD, across six public hospitals in metropolitan Sydney, Australia. CKD-S entails active case finding using the electronic medical record, with nephrologist outreach to admitting teams and kidney nurse provided patient education. Adult inpatients with an admission estimated glomerular filtration rate (eGFR)80 years). Participants will be enrolled between 1 March 2024 and 1 March 2025. Baseline and demographic data will be collected after discharge from the hospital. Participants will be followed up 12 months after discharge using Pharmaceutical Benefits Schedule and Medical Benefits Schedule data, linked via the Australian Institute of Health and Welfare Hub. We will report the proportion of all adults admitted to the hospital who are not already known to a nephrologist, in which a diagnosis of stage 3b–5 CKD is recognised by the CKD-S intervention team, compared with standard care. We will then compare the proportion in each cohort who have an eGFR or urine albumin:creatinine ratio measured, are referred to a nephrologist, and are prescribed guideline-directed therapies over the 12 months following discharge from the hospital.

Ethics and dissemination
The study has ethics approval from the Sydney Local Health District’s Ethics Committee (Concord Hospital Zone). The results of the CKD-S study will be published in peer-reviewed journals and presented at academic conferences.

Trial registration number
ACTRN12624000452594.

Introduction
Several studies have addressed the use of pressure injury preventive measures and bundles for hospitalised patients. However, there is a gap in research regarding the use of pressure injury preventive measures and bundles in the home environment. This scoping review aims to identify, explore and map the international literature on pressure injury preventive measures and bundles in the home and community environments.

Methods and analysis
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews will be used to guide the reporting of this scoping review. The Joanna Briggs Institute guide will inform the methods. A modified version of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols will be used to guide the reporting of this scoping review protocol. An initial search was carried out in July 2024. The search will be conducted in electronic databases such as LILACS, SciELO, Scopus, PubMed, Embase, CINAHL, Cochrane Library and Web of Science. The search will be restricted to studies in English, Portuguese and Spanish, with no time restriction. Additional literature will be retrieved by reviewing the reference lists of the selected studies based on their titles. Two independent reviewers will carry out the data extraction process. Essential details, including the author, references and findings pertinent to the review questions, will be collected. The findings will be displayed through graphs, tables and figures, supplemented by a narrative summary.

Ethics and dissemination
As this review will be conducted using secondary data, ethical approval is not required. Results will be shared with the international scientific community through conference presentations and publication in a high-impact journal.

Study registration
This scoping review was registered with the Open Science Framework registry (osf.io/m5gvn) on 8 August 2024.

Molecola lonafarnib indicata contro rischio morte per progeria

Annals of Internal Medicine, Ahead of Print.