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AIM: To assess the association of age and frailty with clinical outcomes in patients with severe AKI, according to accelerated and standard renal-replacement therapy (RRT) initiation strategies in the STARRT-AKI trial. METHODS: This was a secondary analysis of an international randomized trial. Older age was defined as ≥65 years. Frailty was assessed using the clinical frailty scale (CFS) score and defined as a score ≥5. The primary outcome was all-cause mortality at 90 days. Secondary outcomes included RRT dependence and RRT-free days at 90 days. We used logistic and linear regression and interaction testing to explore the impact of age and frailty on clinical outcomes. RESULTS: Of 2927 patients randomized in the STARRT-AKI trial, 1616 (55.2%) were aged ≥ 65 years (median [IQR] 73.9 [69.4 - 78.9]). Older patients had greater comorbid cardiovascular and chronic kidney disease, were more likely to be surgical admissions and to receive vasopressors at baseline. Older patients had higher 90-day mortality (50.4% vs. 35.6%, adjusted-OR, 1.81 [1.53 to 2.13], p<0.001). There was no significant difference in RRT dependence at 90 days between older and younger patients (8.7% vs. 7.8%, adjusted-OR, 1.21 [0.82 to 1.79], p=0.325). Patients with frailty had higher mortality; but no difference in RRT dependence at 90-days. There was no significant interaction between age and CFS score in relation to mortality, RRT dependence at 90 days, and other secondary outcomes. There was no significant difference in the proportion of patients who received RRT in the standard-strategy stratified by age groups (adjusted-OR, 0.85 [0.67 to 1.08], p=0.180). CONCLUSION: In this secondary analysis of the STARRT-AKI trial, older and frail patients had higher mortality at 90 days; however, there was no difference in RRT dependence. Mortality and RRT dependence were not modified by RRT initiation strategy in older or frail patients.
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Objective: To examine the prognostic values of systemic immune-inflammation indices of hemodialysis (HD) vascular access failure and develop a prediction model for vascular access failure based on the most pertinent systemic immune-inflammation index. Study design: A prospective cohort study. Setting & participants: Patients undergoing autogenous HD vascular access surgeries or arteriovenous graft as a permanent hemodialysis access in a tertiary center in southwest China from January 2020 to June 2022. Predictors: Systemic immune-inflammation indices, including NLR, dNLR, AAPR, SIRI, SII, PNI, PLR, and LIPI, and clinical variables. Outcomes: The outcome was defined as survival of the hemodialysis access, with both occluded and stenotic access being considered as instances of access failure. Analytical approach: Cox proportional hazard regression model. Results: 2690 patients were included in the study population, of whom 658 experienced access failure during the follow-up period. The median duration of survival for HD vascular access was 18 months. The increased systemic immune-inflammation indices, including dNLR, NLR, SII, PNI, SIRI, PLR, and LIPI, are predictive of HD access failure, with SII demonstrating the strongest prognostic value. A simple SII-based prediction model for HD access failure was developed, achieving C-indexes of 0.6314 (95% CI: 0.6249 - 0.6589) and 0.6441 (95% CI: 0.6212 - 0.6670) for predicting 6- and 12-month access survival, respectively. Conclusions: Systemic immune-inflammation indices are significantly and negatively associated with HD vascular access survival. A simple SII-based prediction model was developed and anticipates further improvement through larger study cohort and validation from diverse centers.
Subject(s)
Inflammation , Renal Dialysis , Humans , Male , Middle Aged , Female , Prospective Studies , Inflammation/immunology , Aged , Prognosis , Arteriovenous Shunt, Surgical/adverse effects , Predictive Value of Tests , China , Adult , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/mortality , Kidney Failure, Chronic/immunology , BiomarkersABSTRACT
Successful surgical treatment of drug-resistant epilepsy traditionally relies on the identification of seizure onset zones (SOZs). Connectome-based analyses of electrographic data from stereo electroencephalography (SEEG) may empower improved detection of SOZs. Specifically, connectome-based analyses based on the Interictal Suppression Hypothesis (ISH) posit that when the patient is not having a seizure, SOZs are inhibited by non-SOZs through high inward connectivity and low outward connectivity. However, it is not clear whether there are other motifs that can better identify potential SOZs. Thus, we sought to use unsupervised machine learning to identify network motifs that elucidate SOZs and investigate if there is another motif that outperforms the ISH. Resting-state SEEG data from 81 patients with drug-resistant epilepsy undergoing a pre-surgical evaluation at Vanderbilt University Medical Center were collected. Directed connectivity matrices were computed using the alpha band (8-12Hz). Principal component analysis (PCA) was performed on each patient's connectivity matrix. Each patient's components were analyzed qualitatively to identify common patterns across patients. A quantitative definition was then used to identify the component that most closely matched the observed pattern in each patient. A motif characteristic of the Interictal Suppression Hypothesis (high-inward and low-outward connectivity) was present in all individuals and found to be the most robust motif for identification of SOZs in 64/81 (79%) patients. This principal component demonstrated significant differences in SOZs compared to non-SOZs. While other motifs for identifying SOZs were present in other patients, they differed for each patient, suggesting that seizure networks are patient specific, but the ISH is present in nearly all networks. We discovered that a potentially suppressive motif based on the Interictal Suppression Hypothesis was present in all patients, and it was the most robust motif for SOZs in 79% of patients. Each patient had additional motifs that further characterized SOZs, but these motifs were not common across all patients. This work has the potential to augment clinical identification of SOZs to improve epilepsy treatment.
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Acute kidney injury (AKI) often complicates sepsis and is associated with high morbidity and mortality. In recent years, several important clinical trials have improved our understanding of sepsis-associated AKI (SA-AKI) and impacted clinical care. Advances in sub-phenotyping of sepsis and AKI and clinical trial design offer unprecedented opportunities to fill gaps in knowledge and generate better evidence for improving the outcome of critically ill patients with SA-AKI. In this manuscript, we review the recent literature of clinical trials in sepsis with focus on studies that explore SA-AKI as a primary or secondary outcome. We discuss lessons learned and potential opportunities to improve the design of clinical trials and generate actionable evidence in future research. We specifically discuss the role of enrichment strategies to target populations that are most likely to derive benefit and the importance of patient-centered clinical trial endpoints and appropriate trial designs with the aim to provide guidance in designing future trials.
Subject(s)
Acute Kidney Injury , Sepsis , Humans , Acute Kidney Injury/therapy , Acute Kidney Injury/complications , Critical Illness/therapy , Sepsis/complications , Sepsis/therapy , Clinical Trials as TopicABSTRACT
OBJECTIVES: Among patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant. DESIGN: Secondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722). SETTING: One hundred-fifty-three ICUs in 13 countries. PATIENTS: Altogether 2693 critically ill patients with AKI, of whom 994 were North American, 1143 European, and 556 from Australia and New Zealand (ANZ). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total mean FB to a maximum of 14 days was +7199 mL in North America, +5641 mL in Europe, and +2211 mL in ANZ (p < 0.001). The median time to RRT initiation among patients allocated to the standard strategy was longest in Europe compared with North America and ANZ (p < 0.001; p < 0.001). Continuous RRT was the initial RRT modality in 60.8% of patients in North America and 56.8% of patients in Europe, compared with 96.4% of patients in ANZ (p < 0.001). After adjustment for predefined baseline characteristics, compared with North American and European patients, those in ANZ were more likely to survive to ICU (p < 0.001) and hospital discharge (p < 0.001) and to 90 days (for ANZ vs. Europe: risk difference [RD], -11.3%; 95% CI, -17.7% to -4.8%; p < 0.001 and for ANZ vs. North America: RD, -10.3%; 95% CI, -17.5% to -3.1%; p = 0.007). CONCLUSIONS: Among STARRT-AKI trial centers, significant regional practice variation exists regarding FB, timing of initiation of RRT, and initial use of continuous RRT. After adjustment, such practice variation was associated with lower ICU and hospital stay and 90-day mortality among ANZ patients compared with other regions.
Subject(s)
Acute Kidney Injury , Intensive Care Units , Renal Replacement Therapy , Humans , Acute Kidney Injury/therapy , Male , Renal Replacement Therapy/methods , Renal Replacement Therapy/statistics & numerical data , Female , Middle Aged , New Zealand , North America , Aged , Australia , Europe , Critical Illness/therapy , Treatment OutcomeABSTRACT
Introduction: The prevalence of chronic kidney disease (CKD) in Australia varies substantially across reports. Using a large, nationally representative general practice data source, we determined the contemporary prevalence and staging of CKD in the Australian primary care. Methods: We performed a retrospective, community-based observational study of 2,720,529 adults with ≥1 visit to a general practice participating in the MedicineInsight program and ≥1 serum creatinine measurement (with or without a urine albumin-to-creatinine ratio [UACR] measurement) between 2011 and 2020. CKD prevalence was estimated using 3 definitions based on estimated glomerular filtration rate (eGFR) and UACR measurements with varying degrees of rigidity in terms of the number of measurements assessed to define CKD ("least", "moderate" and "most" rigid). Results: CKD prevalence in the cohort progressively increased over the 10-year study period, irrespective of the method used to define CKD. In 2020, CKD prevalence in the cohort was 8.4%, 4.7%, and 3.1% using the least, moderate, and most rigid definition, respectively. The number of patients with UACR measurements was low such that, among those with CKD in 2020, only 3.8%, 3.2%, and 1.5%, respectively, had both eGFR and UACR measurements available in the corresponding year. Patients in whom both eGFR and UACR measurements were available mostly had moderate or high risk of CKD progression (83.6%, 80.6%, and 76.2%, respectively). Conclusion: In this large, nationally representative study, we observed an increasing trend in CKD prevalence in primary care settings in Australia. Most patients with CKD were at moderate to high risk of CKD progression. These findings highlight the need for early detection and effective management to slow progression of CKD.
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Electroencephalography (EEG) is an indispensable tool in epilepsy, sleep, and behavioral research. In rodents, EEG recordings are typically performed with metal electrodes that traverse the skull into the epidural space. In addition to requiring major surgery, intracranial EEG is difficult to perform for more than a few electrodes, is time-intensive, and confounds experiments studying traumatic brain injury. Here, we describe an open-source cost-effective refinement of this technique for chronic mouse EEG recording. Our alternative two-channel (EEG2) and sixteen-channel high-density EEG (HdEEG) arrays use electrodes made of the novel, flexible 2D nanomaterial titanium carbide (Ti3C2T x ) MXene. The MXene electrodes are placed on the surface of the intact skull and establish an electrical connection without conductive gel or paste. Fabrication and implantation times of MXene EEG electrodes are significantly shorter than the standard approach, and recorded resting baseline and epileptiform EEG waveforms are similar to those obtained with traditional epidural electrodes. Applying HdEEG to a mild traumatic brain injury (mTBI) model in mice of both sexes revealed that mTBI significantly increased spike-wave discharge (SWD) preictal network connectivity with frequencies of interest in the ß-spectral band (12-30â Hz). These findings indicate that the fabrication of MXene electrode arrays is a cost-effective, efficient technology for multichannel EEG recording in mice that obviates the need for skull-penetrating surgery. Moreover, increased preictal ß-frequency network connectivity may contribute to the development of early post-mTBI SWDs.
Subject(s)
Brain Concussion , Brain , Nitrites , Transition Elements , Male , Female , Mice , Animals , Electroencephalography/methods , Electrodes , SkullABSTRACT
Background: Sodium glucose co-transporter 2 (SGLT2) inhibitors reduce the risk of kidney failure and death in patients with chronic kidney disease (CKD) but are underused. We evaluated the number of patients with CKD in Australia that would be eligible for treatment and estimated the number of cardiorenal and kidney failure events that could be averted with improved uptake of SGLT2 inhibitors. Methods: This cross-sectional observational study leveraged nationally representative primary care data from 392 Australian general practices (MedicineInsight) between 1 January 2020 and 31 December 2021. We identified patients that would have met inclusion criteria of key SGLT2 inhibitor trials and applied these data to age and sex-stratified estimates of CKD prevalence for the Australian population (using national census data), estimating the number of preventable events using trial event rates. Key outcomes included cardiorenal events (CKD progression, kidney failure, or death due to cardiovascular or kidney disease) and kidney failure. Findings: In MedicineInsight, 44.2% of adults with CKD would have met CKD eligibility criteria for an SGLT2 inhibitor; baseline use was 4.1%. Applying these data to the Australian population, 230,246 patients with CKD would have been eligible for treatment with an SGLT2 inhibitor. Optimal implementation of SGLT2 inhibitors (75% uptake) could reduce cardiorenal and kidney failure events annually in Australia by 3644 (95% CI 3526-3764) and 1312 (95% CI 1242-1385), respectively. Interpretation: Improved uptake of SGLT2 inhibitors for patients with CKD in Australia has the potential to prevent large numbers of patients experiencing CKD progression or dying due to cardiovascular or kidney disease. Identifying strategies to increase the uptake of SGLT2 inhibitors is critical to realising the population-level benefits of this drug class. Funding: University of New South Wales Scientia Program and Boehringer IngelheimEli Lilly Alliance.
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The global unmet need for kidney replacement therapy means that millions of people die every year as they cannot afford treatment. Peritoneal dialysis (PD) offers comparable survival to haemodialysis and is often more affordable, but one barrier to increasing access is that conventional manufacturing and distribution of PD fluid is costly. Here we report the results from a pilot proof-of-principal study demonstrating for the first time that the Ellen Medical Devices Point-of-Care system can be used by patients to produce sterile PD fluid at the point-of-care. With further development, this low-cost system could offer a solution to the many millions of people around the world who currently cannot afford treatment for kidney failure.
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RATIONALE & OBJECTIVE: Hemodialysis catheter dysfunction is an important problem for patients with kidney failure. The optimal design of the tunneled catheter tip is unknown. This study evaluated the association of catheter tip design with the duration of catheter function. STUDY DESIGN: Observational cohort study using data from the nationwide REDUCCTION trial. SETTING & PARTICIPANTS: 4,722 adults who each received hemodialysis via 1 or more tunneled central venous catheters in 37 Australian nephrology services from December 2016 to March 2020. EXPOSURE: Design of tunneled hemodialysis catheter tip, classified as symmetrical, step, or split. OUTCOME: Time to catheter dysfunction requiring removal due to inadequate dialysis blood flow assessed by the treating clinician. ANALYTICAL APPROACH: Mixed, 3-level accelerated failure time model, assuming a log-normal survival distribution. Secular trends, the intervention, and baseline differences in service, patient, and catheter factors were included in the adjusted model. In a sensitivity analysis, survival times and proportional hazards were compared among participants' first tunneled catheters. RESULTS: Among the study group, 355 of 3,871 (9.2%), 262 of 1,888 (13.9%), and 38 of 455 (8.4%) tunneled catheters with symmetrical, step, and split tip designs, respectively, required removal due to dysfunction. Step tip catheters required removal for dysfunction at a rate 53% faster than symmetrical tip catheters (adjusted time ratio, 0.47 [95% CI, 0.33-0.67) and 76% faster than split tip catheters (adjusted time ratio, 0.24 [95% CI, 0.11-0.51) in the adjusted accelerated failure time models. Only symmetrical tip catheters had performance superior to step tip catheters in unadjusted and sensitivity analyses. Split tip catheters were infrequently used and had risks of dysfunction similar to symmetrical tip catheters. The cumulative incidence of other complications requiring catheter removal, routine removal, and death before removal were similar across the 3 tip designs. LIMITATIONS: Tip design was not randomized. CONCLUSIONS: Symmetrical and split tip catheters had a lower risk of catheter dysfunction requiring removal than step tip catheters. FUNDING: Grants from government (Queensland Health, Safer Care Victoria, Medical Research Future Fund, National Health and Medical Research Council, Australia), academic (Monash University), and not-for-profit (ANZDATA Registry, Kidney Health Australia) sources. TRIAL REGISTRATION: Registered at ANZCTR with study number ACTRN12616000830493. PLAIN-LANGUAGE SUMMARY: Central venous catheters are widely used to facilitate vascular access for life-sustaining hemodialysis treatments but often fail due to blood clots or other mechanical problems that impede blood flow. A range of adaptations to the design of tunneled hemodialysis catheters have been developed, but it is unclear which designs have the greatest longevity. We analyzed data from an Australian nationwide cohort of patients who received hemodialysis via a tunneled catheter and found that catheters with a step tip design failed more quickly than those with a symmetrical tip. Split tip catheters performed well but were infrequently used and require further study. Use of symmetrical rather than step tip hemodialysis catheters may reduce mechanical failures and unnecessary procedures for patients.
Subject(s)
Catheterization, Central Venous , Central Venous Catheters , Adult , Humans , Catheterization, Central Venous/adverse effects , Cohort Studies , Catheters, Indwelling/adverse effects , Australia , Renal Dialysis , Central Venous Catheters/adverse effectsABSTRACT
Introduction: Effective strategies to prevent hemodialysis (HD) catheter dysfunction are lacking and there is wide variation in practice. Methods: In this post hoc analysis of the REDUcing the burden of dialysis Catheter ComplicaTIOns: a national (REDUCCTION) stepped-wedge cluster randomized trial, encompassing 37 Australian nephrology services, 6361 participants, and 9872 catheters, we investigated whether the trial intervention, which promoted a suite of evidence-based practices for HD catheter insertion and management, reduced the incidence of catheter dysfunction, which is defined by catheter removal due to inadequate dialysis blood flow. We also analyzed outcomes among tunneled cuffed catheters and sources of event variability. Results: A total of 873 HD catheters were removed because of dysfunction over 1.12 million catheter days. The raw incidence was 0.91 events per 1000 catheter days during the baseline phase and 0.68 events per 1000 catheter days during the intervention phase. The service-wide incidence of catheter dysfunction was 33% lower during the intervention after adjustment for calendar time (incidence rate ratio = 0.67; 95% confidence interval [CI], 0.50-0.89; P = 0.006). Results were consistent among tunneled cuffed catheters (adjusted incidence rate ratio = 0.68; 95% CI, 0.49-0.94), which accounted for 75% of catheters (n = 7403), 97.4% of catheter exposure time and 88.2% of events (n = 770). Among tunneled catheters that survived for 6 months (21.5% of tunneled catheters), between 2% and 5% of the unexplained variation in the number of catheter dysfunction events was attributable to service-level differences, and 18% to 36% was attributable to patient-level differences. Conclusion: Multifaceted interventions that promote evidence-based catheter care may prevent dysfunction, and patient factors are an important source of variation in events.
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INTRODUCTION: More intensive renal replacement therapy (RRT) has been associated with prolonged mechanical ventilation (MV). However, such finding may be dependent on RRT modality. We hypothesized that, when using continuous renal replacement therapy (CRRT), RRT intensity would not be associated with prolonged MV. METHODS: In a secondary analysis of the Randomized Evaluation of Normal versus Augmented Level (RENAL) Replacement trial comparing different CRRT intensities, we applied Fine-Gray competing risk analysis with time to successful extubation within 28 days as primary outcome. RESULTS: We studied 531 patients in the higher intensity and 551 in the lower intensity group. Higher intensity patients had more hypophosphatemia (66.7 vs. 58.1%; p = 0.004) and more days with hypophosphatemia (2.2 ± 2.8 vs. 1.6 ± 2.2; p < 0.001). There was no difference in the number of patients extubated within 28 days (60.1% vs. 62.4%; adjusted subdistribution hazard ratio [SHR], 0.95 [95% CI, 0.86 to 1.06]) or time to extubation (8 [5-16] vs. 8 [5-15] days; adjusted median difference, 0.65 [95% CI, -0.41 to 1.70]). Among patients from the upper tertile of days with hypophosphatemia, higher intensity CRRT was associated with a lower chance of successful extubation within 28 days (SHR, 0.67 [95% CI, 0.55 to 0.82]; p for heterogeneity = 0.013). CONCLUSIONS: In the RENAL trial, higher intensity CRRT was not associated with delayed extubation. However, it was associated with a greater rate of hypophosphatemia and more days with hypophosphatemia was associated with a lower chance of successful extubation.
Subject(s)
Acute Kidney Injury , Continuous Renal Replacement Therapy , Hypophosphatemia , Humans , Critical Illness/therapy , Renal Replacement Therapy/adverse effects , Hypophosphatemia/etiology , Proportional Hazards Models , Acute Kidney Injury/therapyABSTRACT
BACKGROUND: There is controversy regarding the optimal renal-replacement therapy (RRT) modality for critically ill patients with acute kidney injury (AKI). METHODS: We conducted a secondary analysis of the STandard versus Accelerated Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial to compare outcomes among patients who initiated RRT with either continuous renal replacement therapy (CRRT) or intermittent hemodialysis (IHD). We generated a propensity score for the likelihood of receiving CRRT and used inverse probability of treatment with overlap-weighting to address baseline inter-group differences. The primary outcome was a composite of death or RRT dependence at 90-days after randomization. RESULTS: We identified 1590 trial participants who initially received CRRT and 606 who initially received IHD. The composite outcome of death or RRT dependence at 90-days occurred in 823 (51.8%) patients who commenced CRRT and 329 (54.3%) patients who commenced IHD (unadjusted odds ratio (OR) 0.90; 95% confidence interval (CI) 0.75-1.09). After balancing baseline characteristics with overlap weighting, initial receipt of CRRT was associated with a lower risk of death or RRT dependence at 90-days compared with initial receipt of IHD (OR 0.81; 95% CI 0.66-0.99). This association was predominantly driven by a lower risk of RRT dependence at 90-days (OR 0.61; 95% CI 0.39-0.94). CONCLUSIONS: In critically ill patients with severe AKI, initiation of CRRT, as compared to IHD, was associated with a significant reduction in the composite outcome of death or RRT dependence at 90-days.
Subject(s)
Acute Kidney Injury , Continuous Renal Replacement Therapy , Humans , Acute Kidney Injury/therapy , Critical Illness/therapy , Renal Dialysis , Renal Replacement TherapyABSTRACT
BACKGROUND: Little is known about the relationship between patients' cultural and linguistic backgrounds and patient activation, especially in people with diabetes and chronic kidney disease (CKD). We examined the association between culturally and linguistically diverse (CALD) background and patient activation and evaluated the impact of a codesigned integrated kidney and diabetes model of care on patient activation by CALD status in people with diabetes and CKD. METHODS: This longitudinal study recruited adults with diabetes and CKD (Stage 3a or worse) who attended a new diabetes and kidney disease service at a tertiary hospital. All completed the patient activation measure at baseline and after 12 months and had demographic and clinical data collected. Patients from CALD backgrounds included individuals who spoke a language other than English at home, while those from non-CALD backgrounds spoke English only as their primary language. Paired t-tests compared baseline and 12-month patient activation scores by CALD status. RESULTS: Patients from CALD backgrounds had lower activation scores (52.1 ± 17.6) compared to those from non-CALD backgrounds (58.5 ± 14.6) at baseline. Within-group comparisons showed that patient activation scores for patients from CALD backgrounds significantly improved by 7 points from baseline to 12 months follow-up (52.1 ± 17.6-59.4 ± 14.7), and no significant change was observed for those from non-CALD backgrounds (58.5 ± 14.6-58.8 ± 13.6). CONCLUSIONS: Among patients with diabetes and CKD, those from CALD backgrounds report worse activation scores. Interventions that support people from CALD backgrounds with comorbid diabetes and CKD, such as the integrated kidney and diabetes model of care, may address racial and ethnic disparities that exist in patient activation and thus improve clinical outcomes. PATIENT OR PUBLIC CONTRIBUTION: Patients, caregivers and national consumer advocacy organisations (Diabetes Australia and Kidney Health Australia) codesigned a new model of care in partnership with healthcare professionals and researchers. The development of the model of care was informed by focus groups of patients and healthcare professionals and semi-structured interviews of caregivers and healthcare professionals. Patients and caregivers also provided a rigorous evaluation of the new model of care, highlighting its strengths and weaknesses.
Subject(s)
Diabetes Mellitus , Renal Insufficiency, Chronic , Adult , Humans , Patient Participation , Longitudinal Studies , Cultural Diversity , Diabetes Mellitus/therapy , Renal Insufficiency, Chronic/therapy , KidneyABSTRACT
Acute kidney injury (AKI) occurred in 12.8% of patients undergoing surgery and is associated with increased mortality. Chronic kidney disease (CKD) is a well-known risk for death and cardiovascular disease (CVD). Effects of AKI and CKD on patients undergoing coronary angiography (CAG) remain incompletely defined. The aim of our study was to investigate the relationship between acute and CKD and mortality in patients undergoing CAG. The cohort study included 49,194 patients in the multicenter cohort from January 2007 to December 2018. Cox regression analyses and Fine-Gray proportional subdistribution risk regression analysis are used to examine the association between kidney disease and all-cause and cardiovascular mortality. In the present study, 13,989 (28.4%) patients had kidney disease. During follow-up, 6144 patients died, of which 4508 (73.4%) were due to CVD. AKI without CKD (HR: 1.54, 95% CI: 1.36-1.74), CKD without AKI (HR: 2.02, 95% CI: 1.88-2.17), AKI with CKD (HR: 3.26, 95% CI: 2.90-3.66), and end-stage kidney disease (ESKD; HR: 5.63, 95% CI: 4.40-7.20) were significantly associated with all-cause mortality. Adjusted HR (95% CIs) for cardiovascular mortality was significantly elevated among patients with AKI without CKD (1.78 [1.54-2.06]), CKD without AKI (2.28 [2.09-2.49]), AKI with CKD (3.99 [3.47-4.59]), and ESKD (6.46 [4.93-8.46]). In conclusion, this study shows that acute or CKD is present in up to one-third of patients undergoing CAG and is associated with a substantially increased mortality. These findings highlight the importance of perioperative management of kidney function, especially in patients with CKD.Impact StatementWhat is already known on this subject? Acute kidney injury (AKI) occurred in 12.8% of patients undergoing surgery and is linked to a 22.2% increase in mortality. Chronic kidney disease (CKD) is a well-known risk for death and cardiovascular events. Effects of AKI and CKD on patients undergoing coronary angiography (CAG) remain incompletely defined.What do the results of this study add? This study shows that kidney disease is present in up to one-third of patients undergoing CAG and is associated with a substantially increased mortality. AKI and CKD are independent predicators for mortality in patients undergoing CAG.What are the implications of these findings for clinical practice and/or further research? These findings highlight the importance of perioperative management of kidney function, especially in patients with CKD.
Subject(s)
Acute Kidney Injury , Cardiovascular Diseases , Renal Insufficiency, Chronic , Humans , Coronary Angiography , Cohort Studies , Renal Insufficiency, Chronic/complications , Acute Kidney Injury/etiologyABSTRACT
Rationale & Objective: The benefit-risk profile of rivaroxaban versus warfarin for atrial fibrillation (AF) in patients with chronic kidney disease is uncertain. We compared rivaroxaban with warfarin across the range of kidney function in adults with AF. Study Design: Multicenter retrospective cohort. Setting & Participants: Adults with AF and a measure of estimated glomerular filtration rate (eGFR); using administrative data from 5 jurisdictions across Australia and Canada (2011-2018). Kidney function was categorized as eGFR ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2. Patients receiving dialysis and kidney transplant recipients were excluded. Exposures: New dispensation of either rivaroxaban or warfarin. Outcomes: Composite (1) effectiveness outcome (all-cause death, ischemic stroke, or transient ischemic attack) and (2) major bleeding events (intracranial, gastrointestinal, or other) at 1 year. Analytical Approach: Cox proportional hazards models accounting for propensity score matching were performed independently in each jurisdiction and then pooled using random-effects meta-analysis. Results: 55,568 patients (27,784 rivaroxaban-warfarin user matched pairs; mean age 74 years, 46% female, 33.5% with eGFR <60 mL/min/1.73 m2) experienced a total of 4,733 (8.5%) effectiveness and 1,144 (2.0%) bleeding events. Compared to warfarin, rivaroxaban was associated with greater or similar effectiveness across a broad range of kidney function (pooled HRs of 0.72 [95% CI, 0.66-0.78], 0.78 [95% CI, 0.58-1.06], 0.70 [95% CI, 0.57-0.87], and 0.78 [95% CI, 0.62-0.99]) for eGFR ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2, respectively). Rivaroxaban was also associated with similar risk of major bleeding across all eGFR categories (pooled HRs of 0.75 [95% CI, 0.56-1.00], 1.01 [95% CI, 0.79-1.30], 0.87 [95% CI, 0.66-1.15], and 0.63 [95% CI, 0.37-1.09], respectively). Limitations: Unmeasured treatment selection bias and residual confounding. Conclusions: In adults with AF, rivaroxaban compared with warfarin was associated with lower or similar risk of all-cause death, ischemic stroke and transient ischemic attack and similar risk of bleeding across a broad range of kidney function. Plain-Language Summary: This real-world study involved a large cohort of 55,568 adults with atrial fibrillation from 5 jurisdictions across Australia and Canada. It showed that the favorable safety (bleeding) and effectiveness (stroke or death) profile of rivaroxaban compared with warfarin was consistent across different levels of kidney function. This study adds important safety data on the use of rivaroxaban in patients with reduced kidney function, including those with estimated glomerular filtration rate <30 mL/min/1.73 m2 in whom the risks and benefits of rivaroxaban use is most uncertain. Overall, the study supports the use of rivaroxaban as a safe and effective alternative to warfarin for atrial fibrillation across differing levels of kidney function.
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Reduced nitrogen (N) is central to global biogeochemistry, yet there are large uncertainties surrounding its sources and rate of cycling. Here, we present observations of gas-phase urea (CO(NH2)2) in the atmosphere from airborne high-resolution mass spectrometer measurements over the North Atlantic Ocean. We show that urea is ubiquitous in the lower troposphere in the summer, autumn, and winter but was not detected in the spring. The observations suggest that the ocean is the primary emission source, but further studies are required to understand the responsible mechanisms. Urea is also observed aloft due to long-range transport of biomass-burning plumes. These observations alongside global model simulations point to urea being an important, and currently unaccounted for, component of reduced-N to the remote marine atmosphere. Airborne transfer of urea between nutrient-rich and -poor parts of the ocean can occur readily and could impact ecosystems and oceanic uptake of carbon dioxide, with potentially important climate implications.