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Until recently, structure determination by transmission electron microscopy of beam-sensitive three-dimensional nanocrystals required electron diffraction tomography data collection at liquid-nitrogen temperature, in order to reduce radiation damage. Here it is shown that the novel Timepix detector combines a high dynamic range with a very high signal-to-noise ratio and single-electron sensitivity, enabling ab initio phasing of beam-sensitive organic compounds. Low-dose electron diffraction data (∼0.013 e− Å−2 s−1) were collected at room temperature with the rotation method. It was ascertained that the data were of sufficient quality for structure solution using direct methods using software developed for X-ray crystallography ( XDS, SHELX) and for electron crystallography ( ADT3D/ PETS, SIR2014). [ABSTRACT FROM AUTHOR]

Context: Acute renal failure requiring dialytic support is associated with a high risk of mortality and substantial morbidity.Objectives: To summarize current evidence guiding provision of dialysis for patients with acute renal failure, to make recommendations for management, and to identify areas in which additional research is needed.Data Sources: Systematic searches of peer-reviewed publications in MEDLINE, EMBASE, and All EBM Reviews through October 2007.Study Selection: Randomized controlled trials (RCTs) and prospective cohort studies studying dialytic support in adults with acute renal failure that reported the incidence of clinical outcomes such as mortality, length of stay, need for chronic dialysis, or development of hypotension.Data Extraction: Quality was independently assessed by 2 reviewers using the Jadad score (RCTs) and the Downs and Black checklist (cohort studies). A single reviewer extracted data, which were independently verified by a second reviewer. Results of RCTs were pooled using a random-effects model.Data Synthesis: From 173 retrieved articles, 30 RCTs and 8 prospective cohort studies were eligible. No conclusions could be drawn about optimal indications for or timing of renal replacement. Available data comparing continuous renal replacement therapy (CRRT) with intermittent hemodialysis demonstrated no clinically relevant difference between modalities, including for all-cause mortality (relative risk [RR], 1.10; 95% confidence interval [CI], 0.99-1.23; I2 = 0%) or for the requirement for chronic dialysis treatment in survivors (RR, 0.91; 95% CI, 0.56-1.49; I2 = 0%). For patients treated with CRRT, limited data suggest that bicarbonate may be preferable to other forms of dialysate alkali and that citrate infusion may be an alternative to systemic anticoagulation in patients at high risk of bleeding. Among patients treated with continuous venovenous hemofiltration (CVVHF), the risk of death was lower at doses of 35 mL/kg per hour (RR of death compared with doses of 20 mL/kg per hour, 0.74; 95% CI, 0.63-0.88). The use of unsubstituted cellulosic membranes should be avoided in intermittent hemodialysis (RR of death compared with biocompatible membranes, 1.23; 95% CI, 1.01-1.50).Conclusions: Based on current data, intermittent hemodialysis and CRRT appear to lead to similar clinical outcomes for patients with ARF. If CVVHF is used, a dose of 35 mL/kg per hour should be provided. Given the paucity of good-quality evidence in this important area, additional large randomized trials are needed to evaluate clinically important outcomes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Prophylactic hemofiltration has been reported, in one study, to reduce renal complications and death but necessitates additional up-front health care resource deployment in a critical care setting. We sought to explore the potential scope and cost-effectiveness of this strategy. DESIGN: Economic evaluation using decision analysis. SETTING: Tertiary or quaternary care hospital. PATIENTS: Subjects undergoing angiography at risk for developing contrast nephropathy. INTERVENTION: Prophylactic hemofiltration was compared with intravenous saline. Secondary models incorporated sodium bicarbonate and N-acetylcysteine as comparators. MEASUREMENT AND MAIN RESULTS: The cost per quality-adjusted life year (QALY) gained with hemofiltration compared with intravenous saline in high-risk subjects (mean serum creatinine, 265 micromol/L) was 3,900 US dollars. This finding was sensitive to variations in several important variables. For instance, the cost-effectiveness ratio became less attractive (i.e., >50,000 US dollars/QALY) when hemofiltration was used in lower-risk subjects (serum creatinine, <265 micromol/L). The cost-effectiveness remained <50,000 US dollars/QALY provided that the relative risk of hemofiltration compared with saline alone was below 0.65 (reported relative risk, 0.10). Although based on indirect comparison of clinical efficacy, when N-acetylcysteine or sodium bicarbonate was used as the comparator, the cost per QALY gained for hemofiltration became markedly less attractive (50,100 US dollars and >1,000,000 US dollars), although the relative effectiveness of these three strategies strongly influenced the results. CONCLUSIONS: Use of prophylactic hemofiltration in patients at high risk for contrast nephropathy may be potentially cost-effective only if certain conditions are satisfied, and its attractiveness is materially diminished when compared to other strategies. As this invasive therapy would entail certain immediate resource outlay, before considering its implementation it is crucial to confirm the clinical effectiveness and health care resource consequences of hemofiltration relative to current standards of care in future studies. [ABSTRACT FROM AUTHOR]

Abstract Background The Alberta Kidney Disease Network is a collaborative nephrology research organization based on a central repository of laboratory and administrative data from the Canadian province of Alberta. Description The laboratory data within the Alberta Kidney Disease Network can be used to define patient populations, such as individuals with chronic kidney disease (using serum creatinine measurements to estimate kidney function) or anemia (using hemoglobin measurements). The administrative data within the Alberta Kidney Disease Network can also be used to define cohorts with common medical conditions such as hypertension and diabetes. Linkage of data sources permits assessment of socio-demographic information, clinical variables including comorbidity, as well as ascertainment of relevant outcomes such as health service encounters and events, the occurrence of new specified clinical outcomes and mortality. Conclusion The unique ability to combine laboratory and administrative data for a large geographically defined population provides a rich data source not only for research purposes but for policy development and to guide the delivery of health care. This research model based on computerized laboratory data could serve as a prototype for the study of other chronic conditions.

Background: Women treated with hemodialysis report lower health-related quality of life (HRQoL) compared with men. Whether this is related to sex-specific (biological) (e.g. under-dialysis due to body composition differences) or gender-specific (sociocultural) factors (e.g. greater domestic/caregiver responsibilities for women) is unknown. We examined the association between sex assigned at birth, gender score and HRQoL in individuals initiating conventional and incremental hemodialysis., Methods: In this prospective multi-center cohort study, incident adult hemodialysis patients were recruited between 1 June 2020 and 30 April 2022 in Alberta, Canada. Sex assigned at birth and gender identity were self-reported. Gender-related characteristics were assessed by self-administered questionnaire to derive a composite measure of gender. The primary outcome was change in Kidney Disease Quality of Life 36 physical (PCS) and mental (MCS) component scores after 3 months of hemodialysis., Results: Sixty participants were enrolled (conventional hemodialysis: 14 female, 19 male; incremental hemodialysis: 12 female, 15 male). PCS improved from baseline with conventional ( P  = .01) but not incremental ( P  = .52) hemodialysis in female participants. No difference in MCS was observed by hemodialysis type in female participants. Gender score was not associated with changes in PCS in female participants, irrespective of hemodialysis type. Higher gender score was associated with increased MCS with incremental ( P  = .04), but not conventional ( P  = .14), hemodialysis ( P  = .03 conventional vs incremental) in female participants. No change in PCS or MCS was seen in male participants, irrespective of hemodialysis type or gender score., Conclusion: In this exploratory study, conventional hemodialysis was associated with improved PCS in female participants, while incremental hemodialysis was associated with improved MCS in female participants with more roles and responsibilities traditionally ascribed to women. Large prospective studies are required to further investigate these relationships., Competing Interests: V.J.R.-T is supported by a Kidney Research Scientist Core Education and National Training (KRESCENT) Program Allied Health Doctoral Fellowship (co-sponsored by the Kidney Foundation of Canada, the Canadian Society of Nephrology, and the Canadian Institutes of Health Research). K.A.N. is supported by the Canadian Institutes of Health Research and Heart & Stroke's Women's Heart and Brain Health Mid-career Research Chair., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Source Citation: Perkovic V, Tuttle KR, Rossing P, et al; FLOW Trial Committees and Investigators. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N Engl J Med. 2024;391:109-121. 38785209., Competing Interests: Disclosures: Disclosure forms are available with the article online.

Purpose: Novel interventions for the prevention or treatment of acute kidney injury (AKI) are currently lacking. To facilitate the evaluation and adoption of new treatments, the use of the most appropriate design and endpoints for clinical trials in AKI is critical and yet there is little consensus regarding these issues. We aimed to develop recommendations on endpoints and trial design for studies of AKI prevention and treatment interventions based on existing data and expert consensus., Methods: At the 31st Acute Disease Quality Initiative (ADQI) meeting, international experts in critical care, nephrology, involving adults and pediatrics, biostatistics and people with lived experience (PWLE) were assembled. We focused on four main areas: (1) patient enrichment strategies, (2) prevention and attenuation studies, (3) treatment studies, and (4) innovative trial designs of studies other than traditional (parallel arm or cluster) randomized controlled trials. Using a modified Delphi process, recommendations and consensus statements were developed based on existing data, with > 90% agreement among panel members required for final adoption., Results: The panel developed 12 consensus statements for clinical trial endpoints, application of enrichment strategies where appropriate, and inclusion of PWLE to inform trial designs. Innovative trial designs were also considered., Conclusion: The current lack of specific therapy for prevention or treatment of AKI demands refinement of future clinical trial design. Here we report the consensus findings of the 31st ADQI group meeting which has attempted to address these issues including the use of predictive and prognostic enrichment strategies to enable appropriate patient selection., (© 2024. The Author(s).)