Effects of temperature, chloride and perchlorate salt concentration on the metabolic activity of Deinococcus radiodurans.

The extremophile bacterium Deinococcus radiodurans is characterized by its ability to survive and sustain its activity at high levels of radiation and is considered an organism that might survive in extraterrestrial environments. In the present work, we studied the combined effects of temperature and chlorine-containing salts, with focus on perchlorate salts which have been detected at high concentrations in Martian regolith, on D. radiodurans activity (CO2 production rates) and viability after incubation in liquid cultures for up to 30 days. Reduced CO2 production capacity and viability was observed at high perchlorate concentrations (up to 10% w/v) during incubation at 0 or 25 °C. Both the metabolic activity and viability were reduced as the perchlorate and chloride salt concentration increased and temperature decreased, and an interactive effect of temperature and salt concentration on the metabolic activity was found. These results indicate the ability of D. radiodurans to remain metabolically active and survive in low temperature environments rich in perchlorate.

Epidemiology of Renal Replacement Therapy for Critically Ill Patients across Seven Health Jurisdictions.

INTRODUCTION: Acute kidney injury (AKI) requiring treatment with renal replacement therapy (RRT) is a common complication after admission to an intensive care unit (ICU) and is associated with significant morbidity and mortality. However, the prevalence of RRT use and the associated outcomes in critically patients across the globe are not well described. Therefore, we describe the epidemiology and outcomes of patients receiving RRT for AKI in ICUs across several large health system jurisdictions. METHODS: Retrospective cohort analysis using nationally representative and comparable databases from seven health jurisdictions in Australia, Brazil, Canada, Denmark, New Zealand, Scotland, and the USA between 2006 and 2023, depending on data availability of each dataset. Patients with a history of end-stage kidney disease receiving chronic RRT and patients with a history of renal transplant were excluded. RESULTS: A total of 4,104,480 patients in the ICU cohort and 3,520,516 patients in the mechanical ventilation cohort were included. Overall, 156,403 (3.8%) patients in the ICU cohort and 240,824 (6.8%) patients in the mechanical ventilation cohort were treated with RRT for AKI. In the ICU cohort, the proportion of patients treated with RRT was lowest in Australia and Brazil (3.3%) and highest in Scotland (9.2%). The in-hospital mortality for critically ill patients treated with RRT was almost fourfold higher (57.1%) than those not receiving RRT (16.8%). The mortality of patients treated with RRT varied across the health jurisdictions from 37 to 65%. CONCLUSION: The outcomes of patients who receive RRT in ICUs throughout the world vary widely. Our research suggests that differences in access to and provision of this therapy are contributing factors.

Acute Kidney Injury Duration and 20-Year Risks of CKD and Cardiovascular Disease.

Introduction: Acute kidney injury (AKI) is associated with chronic kidney disease (CKD) and cardiovascular disease (CVD); however, it is unclear whether AKI duration affects the long-term risks of CKD and CVD. Therefore, we performed a population-based cohort study examining the associations between AKI duration and CKD and CVD. Methods: We identified patients with laboratory-recorded AKI in Denmark from 1990 through 2018. AKIs were categorized as rapid reversal AKI (≤48 hours), persistent AKI (2-7 days), and acute kidney disease (AKD) (>7 days). We estimated 20-year risks and adjusted hazard ratios (aHRs) of incident CKD and CVD. Results: The study comprised 169,582 patients with AKI, with 100,478 and 76,838 included in the analysis of CKD and CVD, respectively. The 20-year risks of CKD were 26.3%, 29.5%, and 28.7% for rapid reversal AKI, persistent AKI, and AKD, respectively. Compared with rapid reversal AKI, aHRs were 1.13 (95% confidence interval [CI], 1.08-1.19) for persistent AKI and 1.36 (95% CI, 1.30-1.41) for AKD. Risks and rates of overall CVD were similar for rapid reversal AKI, persistent AKI, and AKD. However, persistent AKI was associated with a slightly increased aHR of heart failure (1.09; 95% CI, 1.02-1.16), and aHRs of heart failure, ischemic heart disease, and peripheral artery disease were slightly increased for AKD (1.09 [95% CI, 1.03-1.15], 1.11 [95% CI, 1.03-1.19], and 1.10 [95% CI, 1.02-1.17], respectively). Conclusion: AKI duration was associated with development of CKD, but not overall CVD; however, rates of heart failure, ischemic heart disease, and peripheral artery disease increased slightly with AKI duration.

Predicting the risks of kidney failure and death in adults with moderate to severe chronic kidney disease: multinational, longitudinal, population based, cohort study.

OBJECTIVE: To train and test a super learner strategy for risk prediction of kidney failure and mortality in people with incident moderate to severe chronic kidney disease (stage G3b to G4). DESIGN: Multinational, longitudinal, population based, cohort study. SETTINGS: Linked population health data from Canada (training and temporal testing), and Denmark and Scotland (geographical testing). PARTICIPANTS: People with newly recorded chronic kidney disease at stage G3b-G4, estimated glomerular filtration rate (eGFR) 15-44 mL/min/1.73 m2. MODELLING: The super learner algorithm selected the best performing regression models or machine learning algorithms (learners) based on their ability to predict kidney failure and mortality with minimised cross-validated prediction error (Brier score, the lower the better). Prespecified learners included age, sex, eGFR, albuminuria, with or without diabetes, and cardiovascular disease. The index of prediction accuracy, a measure of calibration and discrimination calculated from the Brier score (the higher the better) was used to compare KDpredict with the benchmark, kidney failure risk equation, which does not account for the competing risk of death, and to evaluate the performance of KDpredict mortality models. RESULTS: 67 942 Canadians, 17 528 Danish, and 7740 Scottish residents with chronic kidney disease at stage G3b to G4 were included (median age 77-80 years; median eGFR 39 mL/min/1.73 m2). Median follow-up times were five to six years in all cohorts. Rates were 0.8-1.1 per 100 person years for kidney failure and 10-12 per 100 person years for death. KDpredict was more accurate than kidney failure risk equation in prediction of kidney failure risk: five year index of prediction accuracy 27.8% (95% confidence interval 25.2% to 30.6%) versus 18.1% (15.7% to 20.4%) in Denmark and 30.5% (27.8% to 33.5%) versus 14.2% (12.0% to 16.5%) in Scotland. Predictions from kidney failure risk equation and KDpredict differed substantially, potentially leading to diverging treatment decisions. An 80-year-old man with an eGFR of 30 mL/min/1.73 m2 and an albumin-to-creatinine ratio of 100 mg/g (11 mg/mmol) would receive a five year kidney failure risk prediction of 10% from kidney failure risk equation (above the current nephrology referral threshold of 5%). The same man would receive five year risk predictions of 2% for kidney failure and 57% for mortality from KDpredict. Individual risk predictions from KDpredict with four or six variables were accurate for both outcomes. The KDpredict models retrained using older data provided accurate predictions when tested in temporally distinct, more recent data. CONCLUSIONS: KDpredict could be incorporated into electronic medical records or accessed online to accurately predict the risks of kidney failure and death in people with moderate to severe CKD. The KDpredict learning strategy is designed to be adapted to local needs and regularly revised over time to account for changes in the underlying health system and care processes.

Effect of surgery versus chemotherapy in pancreatic cancer patients: a target trial emulation.

BACKGROUND: To estimate the causal effect of surgery vs chemotherapy on survival in patients with T1-3NxM0 pancreatic cancer in a rigorous framework addressing selection bias and immortal time bias. METHODS: We used population-based Danish health-care registries to conduct a cohort study emulating a hypothetical randomized trial to estimate the absolute difference in survival, comparing surgery with chemotherapy. We included pancreatic cancer patients diagnosed during 2008-2021. Exposure was surgery or chemotherapy initiated within a 16-week grace period after diagnosis. At the time of diagnosis, data of each patient were duplicated; one copy was assigned to the surgery protocol, and one copy to the chemotherapy protocol of the hypothetical trial. Copies were censored when the assigned treatment deviated from the observed treatment. To account for informative censoring, uncensored patients were weighted according to confounders. For comparison, we also applied a more conventional analysis using propensity score-based inverse probability weighting. RESULTS: We included 1744 patients with a median age of 68 years: 73.6% underwent surgery, and 18.6% had chemotherapy without surgery; 7.8% received no treatment. The 3-year survival was 39.7% (95% confidence interval [CI] = 36.7% to 42.6%) after surgery and 22.7% (95% CI = 17.7% to 28.4%) after chemotherapy, corresponding to an absolute difference of 17.0% (95% CI = 10.8% to 23.1%). In the conventional survival analysis, this difference was 23.0% (95% CI = 17.0% to 29.0%). CONCLUSION: Surgery was superior to chemotherapy in achieving long-term survival for pancreatic cancer. The difference comparing surgery and chemotherapy was substantially smaller when using the clone-censor-weight approach than conventional survival analysis.

Oral anticoagulant treatment and risk of kidney disease-a nationwide, population-based cohort study.

Background: Direct oral anticoagulants (DOACs) are recommended as first-line treatment of atrial fibrillation. Whether DOAC use is associated with lower risks of kidney complications compared with vitamin K antagonists (VKAs) remains unclear. We examined this association in a nationwide, population-based cohort study. Methods: We conducted a cohort study including patients initiating oral anticoagulant treatment within 3 months after an atrial fibrillation diagnosis in Denmark during 2012-18. Using routinely collected creatinine measurements from laboratory databases, we followed patients in an intention-to-treat approach for acute kidney injury (AKI) and chronic kidney disease (CKD) progression. We used propensity-score weighting to balance baseline confounders, computed weighted risks and weighted hazard ratios (HRs) with 95% confidence intervals (CIs) comparing DOACs with VKAs. We performed several subgroup analyses and a per-protocol analysis. Results: We included 32 781 persons with atrial fibrillation initiating oral anticoagulation (77% initiating DOACs). The median age was 75 years, 25% had a baseline estimated glomerular filtration rate <60 mL/min/1.73 m2, and median follow-up was 2.3 (interquartile range 1.1-3.9) years. The weighted 1-year risks of AKI were 13.6% in DOAC users and 15.0% in VKA users (HR 0.86, 95% CI 0.82; 0.91). The weighted 5-year risks of CKD progression were 13.9% in DOAC users and 15.4% in VKA users (HR 0.85, 95% CI 0.79; 0.92). Results were similar across subgroups and in the per-protocol analysis. Conclusions: Initiation of DOACs was associated with a decreased risk of AKI and CKD progression compared with VKAs. Despite the potential limitations of observational studies, our findings support the need for increased clinical awareness to prevent kidney complications among patients who initiate oral anticoagulants.

Risk factor analysis for a rapid progression of chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a growing global health concern. Identifying individuals in routine clinical care with new-onset CKD at high risk of rapid progression of the disease is imperative to guide allocation of prophylactic interventions, but community-based data are limited. We aimed to examine the risk of rapid progression, kidney failure, hospitalization and death among adults with incident CKD stage G3 and to clarify the association between predefined risk markers and rapid CKD progression. METHODS: Using plasma creatinine measurements for the entire Danish population from both hospitals and primary care, we conducted a nationwide, population-based cohort study, including adults in Denmark with incident CKD stage G3 in 2017-2020. We estimated 3-year risks of rapid progression (defined by a confirmed decline in estimated glomerular filtration rate of ≥5 mL/min/1.73 m2/year), kidney failure, all-cause hospitalization and death. To examine risk markers, we constructed a heat map showing the risk of rapid progression based on predefined markers: albuminuria, sex, diabetes and hypertension/cardiovascular disease. RESULTS: Among 133 443 individuals with incident CKD stage G3, the 3-year risk of rapid progression was 14.6% [95% confidence interval (CI) 14.4-14.8]. The 3-year risks of kidney failure, hospitalization and death were 0.3% (95% CI 0.3-0.4), 53.3% (95% CI 53.0-53.6) and 18.1% (95% CI 17.9-18.4), respectively. In the heat map, the 3-year risk of rapid progression ranged from 7% in females without albuminuria, hypertension/cardiovascular disease or diabetes, to 46%-47% in males and females with severe albuminuria, diabetes and hypertension/cardiovascular disease. CONCLUSION: This population-based study shows that CKD stage G3 is associated with considerable morbidity in a community-based setting and underscores the need for optimized prophylactic interventions among such patients. Moreover, our data highlight the potential of using easily accessible markers in routine clinical care to identify individuals who are at high risk of rapid progression.

Fifteen-year temporal changes in rates of acute kidney injury among children in Denmark.

BACKGROUND: We aimed to examine temporal changes in the annual rate of acute kidney injury (AKI) in Danish children and associated changes in patient characteristics including potential underlying risk factors. METHODS: In this population-based cohort study, we used plasma creatinine measurements from Danish laboratory databases to identify AKI episodes in children aged 0-17 years from 2007 to 2021. For each child, the first AKI episode per calendar year was included. We estimated the annual crude and sex- and age-standardized AKI rate as the number of children with an AKI episode divided by the total number of children as reported by census numbers. Using Danish medical databases, we assessed patient characteristics including potential risk factors for AKI, such as use of nephrotoxic medication, surgery, sepsis, and perinatal factors. RESULTS: In total, 14,200 children contributed with 16,345 AKI episodes over 15 years. The mean annual AKI rate was 148 (95% CI: 141-155) per 100,000 children. From 2007 to 2021, the annual AKI rate demonstrated minor year-to-year variability without any discernible overall trend. The highest AKI rate was recorded in 2007 at 174 (95% CI: 161-187) per 100,000 children, while the lowest rate occurred in 2012 at 129 (95% CI: 118-140) per 100,000 children. In 2021, the AKI rate was 148 (95% CI: 141-155) per 100,000 children. Characteristics of children with AKI were similar throughout the study period. CONCLUSION: The rate of AKI among Danish children was stable from 2007 to 2021 with little variation in patient characteristics over time.

Regional variation in incidence and prognosis of acute kidney injury.

BACKGROUND: Examining regional variation in acute kidney injury (AKI) and associated outcomes may reveal inequalities and possibilities for optimization of the quality of care. Using the Danish medical databases, we examined regional variation in the incidence, follow-up and prognosis of AKI in Denmark. METHODS: Patients with one or more AKI episodes in 2017 were identified using population-based creatinine measurements covering all Danish residents. Crude and sex-and-age-standardized incidence rates of AKI were estimated using census statistics for each municipality. Adjusted hazard ratios (aHR) of chronic kidney disease (CKD), all-cause death, biochemical follow-up and outpatient contact with a nephrology department after AKI were estimated across geographical regions and categories of municipalities, accounting for differences in demographics, comorbidities, medication use, lifestyle and social factors, and baseline kidney function. RESULTS: We identified 63 382 AKI episodes in 58 356 adults in 2017. The regional standardized AKI incidence rates ranged from 12.9 to 14.9 per 1000 person-years. Compared with the Capital Region of Denmark, the aHRs across regions ranged from 1.04 to 1.25 for CKD, from 0.97 to 1.04 for all-cause death, from 1.09 to 1.15 for biochemical follow-up and from 1.08 to 1.49 for outpatient contact with a nephrology department after AKI. Similar variations were found across municipality categories. CONCLUSIONS: Within the uniform Danish healthcare system, we found modest regional variation in AKI incidence. The mortality after AKI was similar; however, CKD, biochemical follow-up and nephrology follow-up after AKI varied across regions and municipality categories.