Faculty Bibliography

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.

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/UNASSIGNED:Moderate kidney dysfunction is independently associated with increased cardiovascular mortality. Sudden cardiac arrest (SCA) accounts for at least 25% of chronic kidney disease (CKD) mortality. METHODS/UNASSIGNED:(2021 CKD-EPI formula). A population-based SCA study in Southern California was used for validation. RESULTS/UNASSIGNED:eGFR drop below 90 increased SCA risk (OR: 1.24, 95% CI: 1.18-1.31). Similar findings were observed in the validation cohort (817 SCA and 3,249 controls), where moderate CKD was associated with SCA (OR: 1.51, 95% CI: 1.16-1.97). CONCLUSION/UNASSIGNED: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.

IMPORTANCE/UNASSIGNED:Chronic pain is common among individuals with dialysis-dependent kidney failure. OBJECTIVE/UNASSIGNED:To evaluate the effectiveness of pain coping skills training (PCST), a cognitive behavioral intervention, on pain interference. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This multicenter randomized clinical trial of PCST vs usual care was conducted across 16 academic centers and 103 outpatient dialysis facilities in the US. Adults undergoing maintenance hemodialysis and experiencing chronic pain were randomly assigned to PCST or usual care in a 1:1 ratio. Participants were followed in the trial for 36 weeks. Enrollment began on January 4, 2021, and follow-up ended on December 21, 2023. INTERVENTIONS/UNASSIGNED:PCST consisting of 12 weekly coach-led sessions via video or telephone conferencing, followed by 12 weeks of daily interactive voice response sessions. Usual care had no trial-driven pain intervention. MAIN OUTCOMES/UNASSIGNED:The primary outcome was pain interference measured with the Brief Pain Inventory (BPI) Interference subscale (score range of 0-10, with higher scores indicating more pain interference). Secondary outcomes included pain intensity, pain catastrophizing, quality of life, depression, and anxiety. RESULTS/UNASSIGNED:A total of 643 participants (mean [SD] age, 60.3 [12.6] years; 288 [44.8%] female) were randomized, with 319 assigned to PCST and 324 assigned to usual care. At week 12 (primary end point), the PCST group had a larger reduction in the BPI Interference score than the usual care group (between-group difference, -0.49; 95% CI, -0.85 to -0.12; P = .009). The effect persisted at week 24 (between-group difference in BPI Interference score, -0.48; 95% CI, -0.86 to -0.11) but was diminished at week 36 (between-group difference in BPI Interference score, -0.34; 95% CI, -0.72 to 0.04). A decrease in BPI Interference score greater than 1 point (minimal clinically important difference) occurred in 143 of 281 participants (50.9%) in the PCST group vs 108 of 295 participants (36.6%) in the usual care group at 12 weeks (odds ratio, 1.79; 95% CI, 1.28-2.49) and 142 of 258 participants (55.0%) in the PCST group vs 113 of 264 participants (42.8%) in the usual care group at 24 weeks (odds ratio, 1.59; 95% CI, 1.13-2.24). Favorable changes with PCST were also apparent for secondary outcomes of pain intensity, quality of life, depression, and anxiety at weeks 12 and/or 24, as well as for pain catastrophizing at weeks 24 and 36. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this randomized clinical trial of patients undergoing maintenance hemodialysis, PCST had benefits on pain interference and other pain-associated outcomes. While the effect on the overall cohort was of modest magnitude, the intervention resulted in a clinically meaningful improvement in pain interference for a substantial proportion of participants. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04571619.

The optimal approach towards managing serum potassium (sK⁺) and hemodialysate potassium concentrations is uncertain. To study this, adults receiving hemodialysis for three months or more with hyperkalemia (pre-dialysis sK⁺ 5.1-6.5 mmol/l) had cardiac monitors implanted and were randomized to either eight weeks of 2.0 mmol/l potassium/1.25 mmol/l calcium dialysate without sodium zirconium cyclosilicate (SZC) (2.0 potassium/noSZC) or 3.0 mmol/l potassium/1.25 mmol/l calcium dialysate combined with SZC (3.0 potassium/SZC) on non-dialysis days to maintain pre-dialysis sK⁺ 4.0-5.5 mmol/l, followed by treatment crossover for another eight weeks. The primary outcome was the rate of adjudicated atrial fibrillation (AF) episodes of at least 2 minutes duration. Secondary outcomes included clinically significant arrhythmias (bradycardia, ventricular tachycardia, and/or asystole) and the proportion of sK⁺ measurements within an optimal window of 4.0-5.5 mmol/l. Among 88 participants (mean age: 57.1 years; 51% male; mean pre-dialysis sK⁺: 5.5 mmol/l) with 25.5 person-years of follow-up, 296 AF episodes were detected in nine patients. The unadjusted AF rate was lower with 3.0 potassium/SZC versus 2.0 potassium/noSZC; 9.7 vs. 13.4/person-year (modeled rate ratio 0.52; 95% confidence interval 0.41-0.65). Clinically significant arrhythmias were reduced with 3.0 potassium/SZC vs. 2.0 potassium/noSZC (6.8 vs. 10.2/person-year modeled rate ratio 0.47; 0.38; 0.58). Fewer sK⁺ measurements outside the optimal window occurred with 3.0 potassium/SZC (modeled odds ratio: 0.27; 0.12-0.35). Hypokalemia was less frequent (33 vs. 58 patients) with 3.0 potassium/SZC compared with 2.0 potassium/noSZC. Thus, in patients with hyperkalemia on maintenance hemodialysis, a combination of hemodialysate potassium 3.0 mmol/l and SZC on non-hemodialysis days reduced the rates of AF, other clinically significant arrhythmias, and post-dialysis hypokalemia compared with hemodialysate potassium 2.0/noSZC.

BACKGROUND:Sudden death accounts for approximately 25% of deaths among maintenance hemodialysis patients, occurring more frequently on hemodialysis days. Higher dialysate bicarbonate (DBIC) may predispose to alkalemia and arrhythmogenesis. METHODS:We conducted a 12-month analysis of session-level data from 66 patients with implantable loop recorders. We fit logistic regression and negative binomial mixed-effects regression models to assess the association of DBIC with clinically significant arrhythmia (ventricular tachycardia ≥115 beats per minute [BPM] for at least 30 seconds, bradycardia ≤40 BPM for at least 6 seconds, or asystole for at least 3 seconds) and reviewer confirmed arrhythmia (RCA—implantable loop recorder-identified or patient-marked event for which a manual review of the stored electrocardiogram tracing confirmed the presence of atrial fibrillation, supraventricular tachycardia, sinus tachycardia with rate >130 BPM, ventricular tachycardia, asystole, or bradycardia). Models adjusted for age, sex, race, hemodialysis vintage, vascular access, and prehemodialysis serum bicarbonate and additionally for serum and dialysate potassium levels. RESULTS:The mean age was 56±12 years, 70% were male, 53% were Black, and 35% were Asian. Fewer RCA episodes were associated with DBIC >35 than 35 mEq/L (incidence rate ratio 0.45 [0.27 to 0.75] and adjusted incident rate ratio 0.54 [0.30 to 0.97]), but the association was not significant when adjusting for serum and dialysate potassium levels (adjusted incident rate ratio, 0.60 [0.32 to 1.11]). Otherwise, no associations between DBIC and arrhythmia were identified. CONCLUSIONS:We observed a lower frequency of RCA with higher DBIC, compared with DBIC of 35 mEql/L, contrary to our original hypothesis, but this association was attenuated in fully adjusted models. Validation of these findings in larger studies is required, with a further need for interventional studies to explore the optimal DBIC concentration.