Faculty Bibliography

BACKGROUND:Moderate kidney dysfunction is independently associated with increased cardiovascular death. Sudden cardiac arrest (SCA) accounts for at least 25% of chronic kidney disease (CKD) death. This study aimed to evaluate the impact of moderate CKD on SCA risk. METHODS:(2021 Chronic Kidney Disease Epidemiology Collaboration formula). A population-based SCA study in southern California was used for validation. RESULTS:estimated glomerular filtration rate drop to <90 increased SCA risk (odds ratio, 1.24 [95% CI, 1.18-1.31]). Similar findings were observed in the validation cohort (817 SCA and 3249 controls), where moderate CKD was associated with SCA (odds ratio, 1.54 [95% CI, 1.18-2.00]). CONCLUSIONS:Moderate CKD is associated with an increased risk of SCA in the general population. Further research into the potential integration of moderate renal dysfunction into SCA risk stratification are warranted.

BACKGROUND:Falls are thought to be common in patients undergoing maintenance hemodialysis, but little is known about their frequency or outcomes. In this prospective study, we sought to increase our knowledge regarding the incidence, timing, circumstances, and outcomes of falls in this population. METHODS:Between January 2021 and April 2023, adults undergoing maintenance hemodialysis from 103 U.S. dialysis facilities were enrolled in the HOPE Consortium trial, which randomized participants with moderate or severe chronic pain to a pain coping skills cognitive behavioral therapy intervention or usual care. Occurrence of falls was a pre-specified trial outcome. The research team inquired about falls at each four-week follow-up visit during the 36-week study. Multivariable regression was used to explore associations of demographic and clinical characteristics, including patient-reported symptoms, with fall risk. RESULTS:Of 643 trial participants, 178 (28%) experienced 293 falls over a cumulative follow-up period of 429 participant-years for an overall rate of 0.68 falls per participant-year (95% CI: 0.61, 0.76). Accidents were the most frequent cause of falls (38%). It was rare for falls to be related to the hemodialysis treatment or to occur in the hemodialysis unit. Of the 293 falls, 36 (12%) were evaluated in the emergency department without subsequent hospitalization, 41 (14%) resulted in a hospital admission, and 19 (7%) led to a fracture. In multivariable analyses, neither demographic characteristics severity of pain symptoms or medication use such as opioids at enrollment was associated with the fall risk. CONCLUSIONS:Falls were common in this cohort of maintenance hemodialysis patients with chronic pain, occurring in 28% of individuals during a planned follow-up of 36 weeks. Falls rarely occurred in the dialysis unit, with the vast majority occurring at participants' homes and due to accidental causes. There was no significant association between patient-reported symptoms or medication use and the risk of subsequent falls. TRIAL REGISTRATION/BACKGROUND:NCT04571619.

IMPORTANCE/UNASSIGNED:Hyperkalemia is a common complication of taking a renin-angiotensin-aldosterone system inhibitor (RAASi). Post hoc analyses of large randomized clinical trials suggested that the addition of sodium-glucose cotransporter 2 inhibitors (SGLT2i) may attenuate this risk. It is unknown if this observation extends to daily clinical practice. OBJECTIVE/UNASSIGNED:To evaluate the association between SGLT2i initiation and hyperkalemia in individuals receiving RAASi with a background of diabetes, heart failure, or chronic kidney disease. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This population-based retrospective cohort study was conducted in Ontario, Canada, from July 1, 2015, to June 30, 2021. The cohort comprised adults 66 years and older who were prescribed a RAASi and had a history of diabetes or heart failure, an estimated glomerular filtration rate of less than 45 mL/min/1.73 m2, and/or a urine albumin to creatinine ratio of greater than 30 mg/mmol. The data were analyzed between March 28, 2023, and March 22, 2024. EXPOSURE/UNASSIGNED:The study exposure was a new prescription of an SGLT2i compared to noninitiation of an SGLT2i. Inverse probability of treatment weighting by a propensity score for the receipt of SGLT2i was used to achieve balance of baseline covariates in both exposure groups. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary study outcome was hyperkalemia, defined as a serum potassium of greater than 5.5 mEq/L or an administrative code for an inpatient or outpatient encounter with hyperkalemia within 1 year of the index date. RESULTS/UNASSIGNED:A total of 20 063 individuals who initiated an SGLT2i (mean [SD] age, 76.9 [6.6] years; 12 020 [59.9%] male) were compared to a pseudopopulation of 19 781 nonusers (mean [SD] age, 76.8 [7.0] years; 11 731 [59.3%] male). In the overall cohort, 95% had diabetes, 17% had heart failure, and 32% had stage 3 to 5 chronic kidney disease. SGLT2i initiation was associated with a lower risk of hyperkalemia (hazard ratio, 0.89 [95% CI, 0.82-0.96]). SGLT2i users had a significantly lower rate of RAASi discontinuation compared to nonusers (36% vs 45%; P < .001). CONCLUSIONS AND RELEVANCE/UNASSIGNED:This cohort study demonstrated that, among individuals with diabetes, heart failure, or chronic kidney disease who were receiving a RAASi, SGLT2i initiation was associated with a lower risk of hyperkalemia and RAASi discontinuation.

RATIONALE & OBJECTIVE/OBJECTIVE:Despite national efforts, the uptake of home dialysis (peritoneal dialysis or home hemodialysis) remains low. Characteristics of the built environment may differentially impact home dialysis use. STUDY DESIGN/METHODS:Retrospective cohort study (2010-2019). SETTING & PARTICIPANTS/METHODS:1,103,695 adults (aged≥18 years) initiating dialysis in the US Renal Data System. EXPOSURE/METHODS:We examined 3 built environment domains based on residential ZIP code: (1) medically underserved areas (MUAs), defined as neighborhoods with limited primary care access; (2) distance to the nearest dialysis facility; and (3) distribution of housing characteristics (structure and overcrowding). OUTCOME/RESULTS:Uptake of home dialysis modalities at dialysis initiation. ANALYTICAL APPROACH/METHODS:We quantified associations between built environment characteristics and home dialysis initiation using multilevel logistic regression stratified by urbanicity type (urban, suburban, small-town, and rural). RESULTS:Among adults initiating dialysis, 40.8% lived in MUAs. Across ZIP codes, the mean percentage of overcrowded housing was 4.2% (SD, 4.7%), and the percentage of detached housing was 61.1% (SD, 21.1%); mean distance to the nearest dialysis facility was 5.5km (SD, 9.1km). Living in MUAs was associated with reduced home dialysis use only in urban (OR, 0.94; 95% CI, 0.91-0.96) and suburban (OR, 0.92; 95% CI, 0.89-0.94) areas. Similarly, housing overcrowding was associated with decreased home dialysis use only in urban (OR, 0.88; 95% CI, 0.86-0.89) and suburban (OR, 0.91; 95% CI, 0.90-0.93) areas. Longer distance to a dialysis facility was the most salient neighborhood factor associated with increased home dialysis use in small towns (OR, 1.14; 95% CI, 1.12-1.16) and rural areas (OR, 1.17; 95% CI, 1.15-1.19). LIMITATIONS/CONCLUSIONS:Housing characteristics were measured at the ZIP code level. CONCLUSIONS:Built environment characteristics associated with home dialysis uptake vary by urbanicity. Policies should address built environment barriers that are specific to urbanicity level. For example, increasing the frequency of dialysate delivery schedules could address housing space constraints in urban and suburban areas, and promoting home dialysis might be more effective for patients living far from dialysis centers in small-town and rural areas.

AIM/OBJECTIVE:SGLT2 inhibitors may be underused in older adults with type 2 diabetes due to concerns about safety and tolerability. This pooled analysis of the CANVAS Program and CREDENCE trial examined the efficacy and safety of canagliflozin according to age. METHODS:Pooled individual participant data from the CANVAS Program (n = 10 142) and CREDENCE trial (n = 4401) were analysed by baseline age (<65 years, 65 to <75 years, and ≥75 years). A range of adjudicated clinical outcomes were assessed, including major adverse cardiovascular events and CKD progression, as well as safety outcomes. Cox proportional hazards models and Fine and Gray competing risk analysis were used. RESULTS:Among the 14 543 participants, 7927 (54.5%) were <65 years, 5281 (36.3%) were 65 to <75 years and 1335 (9.2%) were ≥75 years. Older participants had higher rates of atherosclerotic cardiovascular disease and heart failure, longer diabetes duration and lower mean eGFR. Reductions in cardiovascular and kidney outcomes with canagliflozin were consistent across age categories (all p trend >0.10), although there was some evidence that effects on cardiovascular death and all-cause death were attenuated with older age (p trend = 0.02 and 0.03, respectively). Although the incidence of adverse events increased with age, effects of canagliflozin on safety outcomes including acute kidney injury, volume depletion, urinary tract infections and hypoglycaemia, were not modified by age (all p trend >0.10). CONCLUSIONS:In patients with varying degrees of kidney function, canagliflozin reduced cardiovascular and kidney outcomes, regardless of age, with no additional safety concerns identified in older patients.

BACKGROUND/UNASSIGNED:Chronic kidney disease (CKD) impacts more than 800 million people. It causes significant suffering and disproportionately impacts marginalized populations in the United States. Kidney palliative care has the potential to alleviate this distress, but has not been tested. This pilot study evaluates the feasibility of a randomized clinical trial (RCT) testing the efficacy of integrated kidney palliative and CKD care in an urban safety-net hospital. METHODS/UNASSIGNED:, and are receiving care at our safety net hospital. Participants will be randomized in permuted blocks of two or four to either the intervention group, who will receive monthly ambulatory care visits for six months with a palliative care provider trained in kidney palliative care, or to usual nephrology care. Primary outcomes are feasibility of recruitment, retention, fidelity to the study visit protocol, and the ability to collect outcome data. These outcomes include symptom burden, quality of life, and engagement in advance care planning. DISCUSSION/UNASSIGNED:This pilot RCT will provide essential data on the feasibility of testing integrated palliative care in CKD care in an underserved setting. These outcomes will inform a larger, fully powered trial that tests the efficacy of our kidney palliative care approach. CLINICAL TRIAL REGISTRATION/UNASSIGNED:NCT04998110.

CONTEXT/BACKGROUND:Chronic kidney disease (CKD) disproportionately impacts lower socioeconomic groups and is associated with many symptoms and complex decisions. Integration of Kidney Supportive Care (KSC) with CKD care can address these needs. To our knowledge, this approach has not been described in an underserved population. OBJECTIVES/OBJECTIVE:We describe our adaptation of an ambulatory integrated KSC and CKD clinic for implementation in a safety net hospital. We report our utilization metrics; characteristics of the population served; and visit activities. METHODS:We considered modifications from the perspectives of people with CKD, their providers, and the health system. Modifications were informed by meeting notes with key participants (hospital administrators [n = 5], funders [n = 1], and content experts [n = 2]), as well as literature on palliative care program building, safety net hospitals, and KSC. We extracted utilization data for the first 15 months of the clinic's operations, demographics, clinical characteristics, unmet health related social needs, and symptom burden, measured by the Integrated Palliative Outcome Scale-Renal (total Score, and sub-scores of physical, psychological, and practical impact of CKD) from the electronic health record. Results are reported using descriptive statistics. RESULTS:Adaptions were proactive and done by clinical and administrative leaders. Meetings identified challenges of the safety net setting including people presenting with advanced disease and having several social needs. Modifications to our base model were made in staffing, data collection, and work flow. Show rate was approximately 68%, with a majority of people identifying as Black or Hispanic, and uninsured or on Medicaid. Symptom burden was lower than previous reports, driven by a better psychological sub-score. CONCLUSIONS:We describe a feasible ambulatory care model of KSC in a safety net setting that can serve as a framework for the development of other noncancer palliative care ambulatory clinics. Future work will optimize our model.

BACKGROUND AND AIMS/OBJECTIVE:In the FLOW trial, semaglutide reduced the risks of kidney and cardiovascular (CV) outcomes and death in participants with type 2 diabetes mellitus (T2D) and chronic kidney disease (CKD). These prespecified analyses assessed the effects of semaglutide on CV outcomes and death by CKD severity. METHODS:Participants were randomised to subcutaneous semaglutide 1 mg or placebo weekly. The main outcome was a composite of CV death, non-fatal myocardial infarction (MI) ornon-fatal stroke (CV death/MI/stroke) as well as death due to any cause by baseline CKD severity. CKD was categorised by eGFR < or ≥60 mL/min/1.73 m2, UACR < or ≥300 mg/g or KDIGO risk classification. RESULTS:3533 participants were randomised with a median follow-up of 3.4 years. Low/moderate KDIGO risk was present in 242 (6.9%), while 878 (24.9%) had high and 2412 (68.3%) had very high KDIGO risk. Semaglutide reduced CV death/MI/stroke by 18% (HR 0.82 [95% CI 0.68-0.98]; P = .03), with consistency across eGFR categories, UACR levels and KDIGO risk classification (all P-interaction >.13). Death due to any cause was reduced by 20% (HR 0.80 [0.67-0.95]; P = .01), with consistency across eGFR categories and KDIGO risk class (P-interaction .21 and .23, respectively). The P-interaction treatment effect for death due to any cause by UACR was .01 (<300 mg/g HR 1.17 [0.83-1.65]; ≥300 mg/g HR 0.70 [0.57-0.85]). CONCLUSIONS:Semaglutide significantly reduced the risk of CV death/MI/stroke regardless of baseline CKD severity in participants with T2D.