A CKD Clinical Decision Support System: A Cluster Randomized Clinical Trial in Primary Care Clinics.

Rationale & Objective: The study aimed to develop, implement, and evaluate a clinical decision support (CDS) system for chronic kidney disease (CKD) in a primary care setting, with the goal of improving CKD care in adults. Study Design: This was a cluster randomized trial. Setting & Participants: A total of 32 Midwestern primary care clinics were randomly assigned to either receive usual care or CKD-CDS intervention. Between April 2019 and March 2020, we enrolled 6,420 patients aged 18-75 years with laboratory-defined glomerular filtration rate categories of CKD Stage G3 and G4, and 1 or more of 6 CKD care gaps: absence of a CKD diagnosis, suboptimal blood pressure or glycated hemoglobin levels, indication for angiotensin-converting enzyme inhibitor or angiotensin receptor blocker but not prescribed, a nonsteroidal anti-inflammatory agent on the active medication list, or indication for a nephrology referral. Intervention: The CKD-CDS provided personalized suggestions for CKD care improvement opportunities directed to both patients and clinicians at primary care encounters. Outcomes: We assessed the proportion of patients meeting each of 6 CKD-CDS quality metrics representing care gap resolution after 18 months. Results: The adjusted proportions of patients meeting quality metrics in CKD-CDS versus usual care were as follows: CKD diagnosis documented (26.6% vs 21.8%; risk ratio [RR], 1.17; 95% CI, 0.91-1.51); angiotensin-converting enzyme inhibitor or angiotensin receptor blocker prescribed (15.9% vs 16.1%; RR, 0.95; 95% CI, 0.76-1.18); blood pressure control (20.4% vs 20.2%; RR, 0.98; 95% CI, 0.84-1.15); glycated hemoglobin level control (21.4% vs 22.1%; RR, 1.00; 95% CI, 0.80-1.24); nonsteroidal anti-inflammatory agent not on the active medication list (51.5% vs 50.4%; RR, 1.03; 95% CI, 0.90-1.17); and referral or visit to a nephrologist (38.7% vs 36.1%; RR, 1.02; 95% CI, 0.79-1.32). Limitations: We encountered an overall reduction in expected primary care encounters and obstacles to point-of-care CKD-CDS utilization because of the coronavirus disease 2019 pandemic. Conclusions: The CKD-CDS intervention did not lead to a significant improvement in CKD quality metrics. The challenges to CDS use during the coronavirus disease 2019 pandemic likely influenced these results. Funding: National Institute of Diabetes and Digestive and Kidney Diseases (R18DK118463). Trial Registration: clinicaltrials.gov Identifier: NCT03890588.

This study aimed to improve the management of chronic kidney disease (CKD) through a clinical decision support (CDS) system. It involved 32 primary care clinics and 6,420 patients with CKD who had 1 or more of 6 CKD care improvement opportunities. The CDS provided personalized suggestions to both patients and clinicians about CKD care opportunities during primary care visits. After 18 months, the study found no significant differences between patients in clinics with CKD-CDS compared with usual care in diagnosing CKD, prescribing recommended medications, controlling blood pressure or glycated hemoglobin, nonsteroidal anti-inflammatory agent usage, or nephrology referrals. The coronavirus disease 2019 pandemic may have influenced results by introducing unforeseen implementation challenges, reduced visits, and less than expected CDS exposure.

Symptom Trajectories in the Electronic Health Record during the Transition to Maintenance Dialysis.

How symptoms recorded in the electronic health record change during the transition to dialysis has not been fully explored. We used the Optum deidentified Integrated Claims-Clinical dataset to identify individuals with CKD stages 4 or 5 who transitioned to dialysis. We searched structured data elements from clinical notes, identified by natural language processing, for symptoms recorded across weekly intervals in the 6 months before and after dialysis initiation and estimated changes in the odds of a symptom being recorded with an interrupted time series analysis using segmented logistic regression. The cohort comprised 728 individuals (aged 68±13 years, 44% women, 56% White, 30% Black). Before dialysis initiation, 83% were recorded as having pain, 68% fatigue/weakness, 66% shortness of breath, 61% nausea/vomiting, and 37% difficulty concentrating. Before dialysis initiation, odds of pain being recorded increased (slope: odds ratio [OR] 1.02 per week, 95% confidence interval [CI], 1.01 to 1.03); initiation was associated with a decrease (intercept change: OR 0.70, 95% CI, 0.59 to 0.82). After initiation, odds of pain were unchanged (postdialysis slope: OR 1.00 per week, 95% CI, 0.99 to 1.01), although this represented an improved trajectory relative to the predialysis period (change in slope: OR 0.98 per week, 95% CI, 0.96 to 0.99). For fatigue/weakness, odds increased before initiation (OR 1.03 per week, 95% CI, 1.02 to 1.04) but decreased on initiation (OR 0.62, 95% CI, 0.51 to 0.75) and thereafter (OR 0.98 per week, 95% CI, 0.97 to 0.99), representing a reduction in slope (OR 0.95 per week, 95% CI, 0.94 to 0.97). Patterns for shortness of breath, nausea/vomiting, and difficulty concentrating were similar to those of pain. Thus, the odds of five key symptoms being recorded in the electronic health record increased over time in the 6 months before dialysis initiation, decreased immediately on initiation, and, generally, remained unchanged in the 6 months thereafter.

Increased Access, Persistent Disparities: Trends in Disparities in Peritoneal Dialysis (PD) Use, 2009-2019.

Peritoneal dialysis (PD) use has increased in the United States since 2009, but how this has affected disparities in PD use is unclear. We used data from the United States Renal Data System to identify a cohort of incident dialysis patients from 2009 to 2019. We used logistic regression models to examine how odds of PD use changed by demographic characteristics. The incident PD population increased by 203% from 2009 to 2019, and the odds of PD use increased in every subgroup. PD use increased more among older people because the odds for those aged 75 years or older increased 15% more per 5-year period compared with individuals aged 18-44 years (odds ratio [OR] 1.68, 95% confidence interval [CI], 1.64 to 1.73 versus OR 1.46, 95% CI, 1.42 to 1.50). The odds of PD use increased 5% more per 5-year period among Hispanic people compared with White people (OR 1.58, 95% CI, 1.53 to 1.63 versus OR 1.51, 95% CI, 1.48 to 1.53). There was no difference in odds of PD initiation among people who were Black, Asian, or of another race. The odds of PD use increased 5% more for people living in urban areas compared with people living in nonurban areas (5-year OR 1.54, 95% CI, 1.52 to 1.56 versus 5-year OR 1.46, 95% CI, 1.42 to 1.50). The odds of PD use increased 7% more for people living in socioeconomically advantaged areas compared with people living in more deprived areas (5-year OR 1.60, 95% CI, 1.56 to 1.63 for neighborhoods with lowest Social Deprivation Index versus 5-year OR 1.50, 95% CI, 1.48 to 1.53 in the most deprived areas). Expansion of PD use led to a reduction in disparities for older people and for Hispanic people. Although PD use increased across all strata of socioeconomic deprivation, the gap in PD use between people living in the least deprived areas and those living in the most deprived areas widened.

Association of Nondihydropyridine Calcium Channel Blockers Versus ß-Adrenergic Receptor Blockers With Risk of Heart Failure Hospitalization.

Heart failure (HF) with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are interrelated and often coexisting conditions in older adults. Although equally recommended, nondihydropyridine calcium channel blockers (non-DHP CCBs), such as diltiazem and verapamil, are less often used than ß blockers. Because recent studies suggested that ß-blocker use in both HFpEF and AF may increase the risk for HF, we tested whether non-DHP CCBs were associated with lower HF hospitalization risk than ß blockers. We examined fee-for-service Medicare beneficiaries who were aged ≥66 years, had HFpEF or AF, and newly initiated a ß blocker (n = 83,458) or non-DHP CCB (n = 18,924) from 2014 to 2018. The outcomes of HF hospitalization and all-cause mortality were analyzed using multivariable-adjusted Cox regression in the full cohort and, separately, in the subset without a recent hospital or skilled nursing discharge. Follow-up was analyzed using 2 frameworks: intention-to-treat and censored-at-drug-switch-or-discontinuation. There was a modestly protective association of non-DHP CCBs for the risk of HF hospitalization. Before drug switch or discontinuation, the use of diltiazem or verapamil was associated with decreased risk of HF hospitalization in the full cohort (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.81 to 1.00, p = 0.05) and in the subgroup (HR 0.70, 95% CI 0.56 to 0.89, p = 0.003). However, the association with all-cause mortality tended to favor ß blockers, including in the intention-to-treat analysis (HR 1.21, 95% CI 1.17 to 1.25, p <0.001). In conclusion, compared with ß blockers, the initiation of diltiazem or verapamil in patients with HFpEF or AF may be associated with fewer HF hospitalization events but also with more all-cause deaths.

Association Between CKD and Major Hemorrhage in Older Persons: Data From the Aspirin in Reducing Events in the Elderly Randomized Trial.

Introduction: Data on the association between chronic kidney disease (CKD) and major hemorrhage in older adults are lacking. Methods: We used data from a double-blind randomized controlled trial of aspirin in persons aged ≥ 70 years with prospective capture of bleeding events, including hemorrhagic stroke and clinically significant bleeding. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m2 and/or urinary albumin-to-creatinine ratio (UACR) ≥ 3 mg/mmol (26.6 mg/g). We compared bleeding rates in those with and without CKD, undertook multivariable analyses, and explored effect modification with aspirin. Results: Of 19,114 participants, 17,976 (94.0%) had CKD status recorded, of whom 4952 (27.5%) had CKD. Participants with CKD had an increased rate of major bleeding events compared with those without CKD (10.4/1000 vs. 6.3/1000 person-years [py], respectively) and increased bleeding risk (risk ratio [RR] 1.60; 95% confidence interval [CI]: 1.40, 1.90 for eGFR < 60 ml/min per 1.73 m2) and RR (2.10; 95% CI: 1.70, 2.50) for albuminuria. In adjusted analyses, CKD was associated with a 35% increased risk of bleeding (hazard ratio [HR] 1.37; 95% CI: 1.15, 1.62; P < 0.001). Other risk factors were older age, hypertension, smoking, and aspirin use. There was no differential effect of aspirin on bleeding by CKD status (test of interaction P = 0.65). Conclusion: CKD is independently associated with an increased risk of major hemorrhage in older adults. Increased awareness of modifiable risk factors such as discontinuation of unnecessary aspirin, blood pressure control, and smoking cessation in this group is warranted.

Association of polygenic scores with chronic kidney disease phenotypes in a longitudinal study of older adults.

Risk of chronic kidney disease (CKD) is influenced by environmental and genetic factors and increases sharply in individuals 70 years and older. Polygenic scores (PGS) for kidney disease-related traits have shown promise but require validation in well-characterized cohorts. Here, we assessed the performance of recently developed PGSs for CKD-related traits in a longitudinal cohort of healthy older individuals enrolled in the Australian ASPREE randomized controlled trial of daily low-dose aspirin with CKD risk at baseline and longitudinally. Among 11,813 genotyped participants aged 70 years or more with baseline eGFR measures, we tested associations between PGSs and measured eGFR at baseline, clinical phenotype of CKD, and longitudinal rate of eGFR decline spanning up to six years of follow-up per participant. A PGS for eGFR was associated with baseline eGFR, with a significant decrease of 3.9 mL/min/1.73m2 (95% confidence interval -4.17 to -3.68) per standard deviation (SD) increase of the PGS. This PGS, as well as a PGS for CKD stage 3 were both associated with higher risk of baseline CKD stage 3 in cross-sectional analysis (Odds Ratio 1.75 per SD, 95% confidence interval 1.66-1.85, and Odds Ratio 1.51 per SD, 95% confidence interval 1.43-1.59, respectively). Longitudinally, two separate PGSs for eGFR slope were associated with significant kidney function decline during follow-up. Thus, our study demonstrates that kidney function has a considerable genetic component in older adults, and that new PGSs for kidney disease-related phenotypes may have potential utility for CKD risk prediction in advanced age.

Association of the End-Stage Renal Disease Treatment Choices Payment Model With Home Dialysis Use at Kidney Failure Onset From 2016 to 2022.

Importance: The Centers for Medicare & Medicaid Services designed a mandatory payment model to incentivize home dialysis use: the End-Stage Renal Disease Treatment Choices (ETC). Outpatient dialysis facilities and health care professionals providing nephrology services were randomly assigned to ETC participation at the hospital referral region level. Objective: To assess the association between ETC and home dialysis use in the incident dialysis population in its first 18 months of implementation. Design, Setting, and Participants: A cohort study with controlled, interrupted time series analysis of the US End-Stage Renal Disease Quality Reporting System database was conducted, using generalized estimating equations. All adults initiating home-based dialysis in the US between January 1, 2016, and June 30, 2022, without a prior kidney transplant were included in the analysis. Exposures: Prior to vs after ETC onset in January 1, 2021, and random assignment to ETC participation of facilities and health care professionals involved in patient care. Main Outcomes and Measures: Percentage of patients started on incident home dialysis and yearly change in percentage initiating home dialysis. Results: A total of 817 177 adults initiated home dialysis during the study period, of whom 750 314 were included in the study cohort. The cohort included 41.4% women; 26.2% of the patients were Black, 17.4% were Hispanic, and 49.1% were White. Approximately half (49.6%) of the patients were aged at least 65 years. A total of 31.2% received care from health care professionals assigned to ETC participation, and 33.6% had Medicare fee-for-service coverage. Overall, home dialysis use increased from 10.0% in January 2016 to 17.4% in June 2022. Home dialysis use increased more in ETC markets than in non-ETC markets after January 2021 (by 1.07%; 95% CI, 0.16%-1.97%). The rate of increase in home dialysis use in the entire cohort nearly doubled after January 2021 to 1.66% per year (95% CI, 1.14%-2.19%) compared with before 2021, when the rate was 0.86% per year (95% CI, 0.75%-0.97%), but the difference in rate of increase in home dialysis use was not significant between ETC and non-ETC markets. Conclusions and Relevance: This study noted that, although the overall rate of dialysis use at home was greater after ETC implementation, the increase occurred more among patients in ETC markets than among those in non-ETC markets. These findings suggest that federal policy and financial incentives affected care for the entire incident dialysis population in the US.

GFR Variability, Survival, and Cardiovascular Events in Older Adults.

Rationale & Objective: Variability in estimated glomerular filtration rate (eGFR) over time is often observed, but it is unknown whether this variation is clinically important. We investigated the association between eGFR variability and survival free of dementia or persistent physical disability (disability-free survival) and cardiovascular disease (CVD) events (myocardial infarction, stroke, hospitalization for heart failure, or CVD death). Study Design: Post hoc analysis. Setting & Participants: 12,549 participants of the ASPirin in Reducing Events in the Elderly trial. Participants were without documented dementia, major physical disability, previous CVD, and major life-limiting illness at enrollment. Predictors: eGFR variability. Outcomes: Disability-free survival and CVD events. Analytical Approach: eGFR variability was estimated using the standard deviation of eGFR measurements obtained from participants' baseline, first, and second annual visits. Associations between tertiles of eGFR variability with disability-free survival and CVD events occurring after the eGFR variability estimation period were examined. Results: During median follow-up of 2.7 years after the second annual visit, 838 participants died, developed dementia, or acquired a persistent physical disability; 379 had a CVD event. The highest tertile of eGFR variability had an increased risk of death/dementia/disability (HR, 1.35; 95% CI, 1.14-1.59) and CVD events (HR, 1.37; 95% CI, 1.06-1.77) compared with the lowest tertile after covariate adjustment. These associations were present in patients with and without chronic kidney disease at baseline. Limitations: Limited representation of diverse demographics. Conclusions: In older, generally healthy adults, higher variability in eGFR over time predicts increased risk of future death/dementia/disability and CVD events.

Hemodialysis Access Type and Access Patency Loss: An Observational Cohort Study.

Rationale & Objective: Access patency outcomes for arteriovenous fistulas (AVFs) as compared with arteriovenous grafts (AVGs) in patients receiving hemodialysis (HD) who have achieved a functioning permanent access are not fully explored. Study Design: Observational cohort study. Setting & Population: Fee-for-service Medicare beneficiaries aged ≥18 years with kidney failure who were newly using a permanent access for maintenance HD from the United States Renal Data System (2010-2015). Patients using an oral anticoagulant were excluded. Exposure: AVG or AVF. Outcomes: Loss of primary unassisted, primary assisted, and secondary patency. Analytical Approach: Outcomes were characterized using cumulative incidence curves, and HRs adjusted for sociodemographic and clinical factors were estimated for the comparison of AVF versus AVG. Results: The cohort included 60,329 and 17,763 patients newly using an AVF and AVG, respectively, for HD. Over 3 years of follow-up, AVG users, compared to AVF users, had a higher cumulative incidence of loss of primary unassisted patency (87% vs 69%; HR, 1.56; 95% CI, 1.52-1.60), loss of primary assisted patency (69% vs 25%; HR, 3.79; 95% CI, 3.67-3.92), and loss of secondary patency (22% vs 10%; HR, 2.03; 95% CI, 1.92-2.16). Stratified analyses revealed differences by subgroups; in particular, incidence of patency loss was higher among patients who underwent prior interventions to maintain prefunctional access patency and Black patients. Limitations: This analysis focused on outcomes occurring after first successful use of a permanent access and thus does not inform about risk of patency loss during access maturation. Conclusions: Among patients with kidney failure who successfully used a permanent access for HD, patency loss was consistently substantially higher in those using AVGs compared with AVFs. New interventions, such as prophylactic drugs, are needed to improve access longevity and reduce the need for invasive interventions, particularly among patients unable to receive a fistula.

Impact of donor kidney biopsy on kidney yield and posttransplant outcomes.

Procurement biopsy is performed to determine kidney quality, but evidence supporting such association is poor. We investigated the impact of glomerulosclerosis percentage (GS%) on kidney yield and patient outcomes. Information on deceased kidney donors from July 1, 2017, to June 30, 2019, was collected. Association between GS% and kidney yield (number of kidneys procured per donor) and posttransplant graft and patient outcomes were studied. Maximal GS% and minimal GS% were calculated to determine the relationship between GS% and kidney yield; minimal GS% only for correlation with posttransplant outcomes. Multinomial logistic regression and Cox models with least absolute shrinkage and selection operator were used to analyze the association of GS% with kidney yield and posttransplant outcomes, respectively. The kidney yield was 1.63 when maximal GS% and minimal GS% were <5%, but was 0.88 when both GS% were >20%. The hazard ratio for graft failure 1 year after transplant was 1.05 when minimal GS% was 16% to 20%, but was 1.3 for GS% of >20%. The hazard ratio for mortality increased from 1 to 1.2 when minimal GS% reached >20%. In summary, higher GS% was associated with lower kidney yield and inferior posttransplant outcomes. Incorporation of GS% into Scientific Registry of Transplant Recipients models may reassure organ procurement organizations and transplant centers pursuing kidneys with relatively high GS% levels, thereby reducing kidney discard rates.

Impact of Donor Liver Macrovesicular Steatosis on Deceased Donor Yield and Posttransplant Outcome.

BACKGROUND: The Scientific Registry of Transplant Recipients (SRTR) had not traditionally considered biopsy results in risk-adjustment models, yet biopsy results may influence outcomes and thus decisions regarding organ acceptance. METHODS: Using SRTR data, which includes data on all donors, waitlisted candidates, and transplant recipients in the United States, we assessed (1) the impact of macrovesicular steatosis on deceased donor yield (defined as number of livers transplanted per donor) and 1-y posttransplant graft failure and (2) the effect of incorporating this variable into existing SRTR risk-adjustment models. RESULTS: There were 21 559 donors with any recovered organ and 17 801 liver transplant recipients included for analysis. Increasing levels of macrovesicular steatosis on donor liver biopsy predicted lower organ yield: ≥31% macrovesicular steatosis on liver biopsy was associated with 87% to 95% lower odds of utilization, with 55% of these livers being discarded. The hazard ratio for graft failure with these livers was 1.53, compared with those with no pretransplant liver biopsy and 0% to 10% steatosis. There was minimal change on organ procurement organization-specific deceased donor yield or program-specific posttransplant outcome assessments when macrovesicular steatosis was added to the risk-adjustment models. CONCLUSIONS: Donor livers with macrovesicular steatosis are disproportionately not transplanted relative to their risk for graft failure. To avoid undue risk aversion, SRTR now accounts for macrovesicular steatosis in the SRTR risk-adjustment models to help facilitate use of these higher-risk organs. Increased recognition of this variable may also encourage further efforts to standardize the reporting of liver biopsy results.

Prescribing Patterns of Direct-Acting Oral Anticoagulants in Patients With Atrial Fibrillation and Chronic Kidney Disease: A Retrospective Cohort Analysis.

BACKGROUND: The association of patient and prescriber characteristics with use of warfarin versus direct-acting oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and chronic kidney disease (CKD) is not well studied. METHODS: The 20% Centers for Medicare & Medicaid Services Parts A, B, and D claims data from 2010 to 2017 were used to identify patients with stage 3, 4, or 5 CKD and AF who received a DOAC (apixaban, dabigatran, rivaroxaban) or warfarin. Prescribers were categorized as cardiologists, primary care providers (PCPs), and others. Using logistic regression, we estimated odds ratios (ORs) for the association of baseline characteristics and prescriber specialty with first use of a DOAC, relative to warfarin. RESULTS: We identified 22,739 individuals with CKD who were newly initiated on oral anticoagulation for AF. New DOAC prescriptions increased from 490 in 2011 to 3261 in 2017, and displaced warfarin over time (1849, 2011; 945, 2017). By Q4 of 2014, cardiologists prescribed DOACs as initial treatment more frequently than warfarin, but non-cardiologists did not do so until 2015. As of 2017, apixaban was the most widely prescribed anticoagulant, comprising 56% and 50% of prescriptions by cardiologists and non-cardiologists, respectively. PCPs (OR 0.54, 0.51-0.58) and other providers (OR 0.55, 0.51-0.59) were less likely than cardiologists to prescribe DOACs. CONCLUSIONS: DOAC prescriptions, particularly apixaban, increased over time and gradually displaced warfarin. The total number of patients with AF and CKD receiving anticoagulation increased over time. Cardiologists increased DOAC prescriptions more rapidly than non-cardiologists.

Associations of COVID-19 Outcomes with Dialysis Modalities and Settings.

How maintenance dialysis modality, dialysis setting, and residence in a nursing facility have jointly associated with coronavirus disease 2019 (COVID-19)-related outcomes in the United States is relevant to future viral outbreaks. Using Medicare claims, we determined the incidence of COVID-19-related infection, hospitalization, and death between March 15, 2020 and June 5, 2021. The exposure was one of five combinations of dialysis modality and care setting: in-facility hemodialysis without a recent history of skilled nursing facility care, in-facility hemodialysis with a recent history of skilled nursing facility care, hemodialysis in a skilled nursing facility, home hemodialysis, and (home) peritoneal dialysis. Patient-weeks were pooled to estimate the adjusted associations of event incidence with each dialysis modality/setting during four intervals in 2020-2021. Relative to in-facility hemodialysis without a recent history of skilled nursing facility care, home dialysis was associated with 36%-60% lower odds of all events during weeks 12-23 of 2020; 24%-37% lower odds of all events during weeks 24-37 of 2020; 20%-33% lower odds of infection and hospitalization during the winter of 2020-2021; and similar odds of all events thereafter. In contrast, exposure to skilled nursing facilities was associated with 570%-1140% higher odds of all events during spring of 2020, although excess risk attenuated as the pandemic transpired, especially among patients who received hemodialysis in skilled nursing facilities. In conclusion, home dialysis was associated with lower risks of COVID-19 diagnosis, hospitalization, and death until vaccines were available, whereas care in skilled nursing facilities was associated with higher risks.

Hemodialysis Vascular Access and Risk of Major Bleeding, Thrombosis, and Cardiovascular Events: A Cohort Study.

Rationale & Objective: The risks of major bleeding, thrombosis, and cardiovascular events are elevated in patients receiving maintenance hemodialysis (HD). Our objective was to compare the risk of these outcomes in HD according to the permanent vascular access type. Study Design: Observational cohort study. Setting & Participants: Using data from the United States Renal Data System (2010-2015), we included patients with kidney failure who were greater than 18 years, had Medicare as the primary payer, were not using an oral anticoagulant, and were newly using an arteriovenous (AV) access for HD. Exposure: AV graft (AVG) or AV fistula (AVF). Outcomes: Major bleeding, venous thromboembolism, ischemic stroke, myocardial infarction, cardiovascular death, and critical limb ischemia. Analytical Approach: Comparing 17,763 AVG and 60,329 AVF users, we estimated the 3-year incidence rates and incidence rate ratios (IRRs) of each outcome using Poisson regression. IRRs were adjusted for sociodemographic and clinical covariates. Results: The use of an AVG, compared with that of an AVF, was associated with an increased risk of venous thromboembolism (10.8 vs 5.3 events per 100 person-years; adjusted IRR, 1.74; 95% CI, 1.63-1.85) but not with the risk of major bleeding (IRR, 1.04; 95% CI, 0.93-1.17). The use of an AVG was also potentially associated with a slightly increased risk of cardiovascular death (IRR, 1.09; 95% CI, 1.01-1.16). Limitations: This analysis focused on patients with a functioning AV access; adverse events that may occur during access maturation should also be considered when selecting a vascular access. Conclusions: The use of an AVG, relative to an AVF, in HD is associated with an increased risk of venous thromboembolism. Given recent guidelines emphasizing selection of the "right access" for the "right patient," the results of this study should potentially be considered as one additional factor when selecting the optimal access for HD.

CKD Biomarkers, Cognitive Impairment, and Incident Dementia in an Older Healthy Cohort.

Background: CKD is a risk factor for cognitive impairment (CI), but reports of individual associations of eGFR and albuminuria with CI and incident dementia in healthier, older, longitudinal populations are lacking. Our goal was to estimate these associations in a large cohort of older healthy persons. Methods: In a longitudinal cohort study of older persons without prior cardiovascular disease, we estimated the associations between baseline eGFR (in ml/min per 1.73 m2) and albuminuria, measured as urine albumin-creatinine ratio (UACR; in mg/mmol) and cognitive test scores, declines in cognitive test scores, and incident dementia using adjusted linear and linear mixed models. Cox proportional hazards regression models assessed the association between baseline kidney function and incident CI no dementia (CIND) or dementia at a median of 4.7 years. Results: At baseline, among 18,131 participants, median age was 74 years, eGFR was 74 (IQR, 63-84) ml/min per 1.73 m2, UACR was 0.8 (IQR, 0.5-1.5) mg/mmol (7.1 [4.4-13.3] mg/g), and 56% were female. Baseline eGFR was not associated with performance on any cognitive tests in cross-sectional analysis, nor was incident CIND or dementia over a median follow-up of 4.7 years. However, baseline UACR ≥3 mg/mmol (≥26.6 mg/g) was significantly associated with lower baseline scores and larger declines on the Modified Mini-Mental State Exam, verbal memory and processing speed tests, and with incident CIND (hazard ratio [HR], 1.19; 95% CI, 1.07 to 1.33) and dementia (HR, 1.32; 95% CI, 1.06 to 1.66). Conclusion: Mild albuminuria was associated with worse baseline cognitive function, cognitive decline, and increased risk for incident CIND and dementia. Screening global cognitive tests for older persons with UACR ≥3 mg/mmol could identify those at elevated risk of cognitive decline and dementia.

Apixaban Dosing Patterns Versus Warfarin in Patients With Nonvalvular Atrial Fibrillation Receiving Dialysis: A Retrospective Cohort Study.

BACKGROUND & OBJECTIVES: Comparison of clinical outcomes across anticoagulation regimens using different apixaban dosing or warfarin is not well-defined in patients with nonvalvular atrial fibrillation (AF) who are receiving dialysis. This study compared these outcomes in a US national cohort of patients with kidney failure receiving maintenance dialysis. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Patients receiving dialysis represented in the US Renal Data System database 2013-2018 who had AF and were treated with apixaban or warfarin. EXPOSURE: First prescribed treatment with apixaban dosed according to the label, apixaban dosed below the label, or warfarin. OUTCOME: Ischemic stroke/systemic embolism, major bleeding, and all-cause mortality. ANALYTICAL APPROACH: Cox proportional hazards models with inverse probability of treatment weighting. Analyses simulating an intention-to-treat (ITT) approach as well as those incorporating censoring at drug switch or discontinuation (CAS) were also implemented. Inverse probability of censoring weighting was used to account for possible informative censoring. RESULTS: Among 17,156 individuals, there was no difference in risk of stroke/systemic embolism among the label-concordant apixaban, below-label apixaban, and warfarin treatment groups. Both label-concordant (HR, 0.67 [95% CI, 0.55-0.81]) and below-label (HR, 0.68 [95% CI, 0.55-0.84]) apixaban dosing were associated with a lower risk of major bleeding compared with warfarin in ITT analyses. Compared with label-concordant apixaban, below-label apixaban was not associated with a lower bleeding risk (HR, 1.02 [95% CI, 0.78-1.34]). In the ITT analysis of mortality, label-concordant apixaban dosing was associated with a lower risk versus warfarin (HR, 0.85 [95% CI, 0.78-0.92]) while there was no significant difference in mortality between below-label dosing of apixaban and warfarin (HR, 0.97 [95% CI, 0.89-1.05]). Overall, results were similar for the CAS analyses. LIMITATIONS: Study limited to US Medicare beneficiaries; reliance on administrative claims to ascertain outcomes of AF, stroke, and bleeding; likely residual confounding. CONCLUSIONS: Among patients with nonvalvular AF undergoing dialysis, warfarin is associated with an increased risk of bleeding compared with apixaban. The risk of bleeding with below-label apixaban was not detectably less than with label-concordant dosing. Label-concordant apixaban dosing is associated with a mortality benefit compared to warfarin. Label-concordant dosing, rather than reduced-label dosing, may offer the most favorable benefit-risk trade-off for dialysis patients with nonvalvular AF.