Faculty Bibliography

INTRODUCTION:Relationships between glycemic-lowering effects of sodium glucose co-transporter 2 inhibitors and impact on kidney and cardiovascular outcomes are uncertain. RESEARCH DESIGN AND METHODS:We analyzed 4395 individuals with prebaseline and postbaseline hemoglobin A1c (HbA1c) randomized to canagliflozin (n=2193) or placebo (n=2202) in The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation trial. Effects on HbA1c were assessed using mixed models. Mediation of treatment effects by achieved glycemic control was analyzed using proportional hazards regression with and without adjustment for achieved HbA1c. End points included combined kidney or cardiovascular death, end-stage kidney disease or doubling of serum creatinine (primary trial outcome), and individual end point components. RESULTS:, overall HbA1c (canagliflozin vs placebo) decreased by -0.24%, -0.14%, and -0.08% respectively and likelihood of >0.5% decrease in HbA1c decreased with ORs of 1.47 (95% CI 1.27 to 1.67), 1.12 (0.94 to 1.33) and 0.99 (0.83 to 1.18), respectively. Adjustment for postbaseline HbA1c marginally attenuated canagliflozin effects on primary and kidney composite outcomes: unadjusted HR 0.67 (95% CI 0.57 to 0.80) and 0.66 (95% CI 0.53 to 0.81); adjusted for week 13 HbA1c, HR 0.71 (95% CI 0.060 to 0.84) and 0.68 (95% CI 0.55 to 0.83). Results adjusted for time-varying HbA1c or HbA1c as a cubic spline were similar and consistent with preserved clinical benefits across a range of excellent and poor glycemic control. CONCLUSIONS:The glycemic effects of canagliflozin are attenuated at lower eGFR but effects on kidney and cardiac end points are preserved. Non-glycemic effects may be primarily responsible for the kidney and cardioprotective benefits of canagliflozin.22.

BACKGROUND:In contrast to guidelines related to lipid therapy in other areas, 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend conducting a lipid profile upon diagnosis of chronic kidney disease (CKD) and treating all patients older than 50 years without defining a target for lipid levels. We evaluated multinational practice patterns for lipid management in patients with advanced CKD under nephrology care. METHODS:We analyzed lipid-lowering therapy (LLT), LDL- cholesterol (LDL-C) levels, and nephrologist-specified LDL-C goal upper limits in adult patients with eGFR < 60 ml/min from nephrology clinics in Brazil, France, Germany, and the United States (2014-2019). Models were adjusted for CKD stage, country, cardiovascular risk indicators, sex, and age. RESULTS:LLT treatment differed significantly by country, from 51% in Germany to 61% in the US and France (p = 0.002) for statin monotherapy. For ezetimibe with or without statins, the prevalence was 0.3% in Brazil to 9% in France (< 0.001). Compared with patients not taking lipid-lowering therapy, LDL-C was lower among treated patients (p < 0.0001) and differed significantly by country (p < 0.0001). At the patient level, the LDL-C levels and statin prescription did not vary significantly by CKD stage (p = 0.09 LDL-C and p = 0.24 statin use). Between 7-23% of untreated patients in each country had LDL-C ≥ 160 mg/dL. Only 7-17% of nephrologists believed that LDL-C should be < 70 mg/dL. CONCLUSION/CONCLUSIONS:There is substantial variation in practice patterns regarding LLT across countries but not across CKD stages. Treated patients appear to benefit from LDL-C lowering, yet a significant proportion of hyperlipidemia patients under nephrologist care are not receiving treatment.

Peritoneal dialysis (PD) as an AKI treatment in adults was widely accepted in critical care settings well into the 1980s. The advent of extracorporeal continuous KRT led to widespread decline in the use of PD for AKI across high-income countries. The lack of familiarity and comfort with the use of PD in critical care settings has also led to lack of use even among those receiving maintenance PD. Many critical care units reflexively convert patients receiving maintenance PD to alternative dialysis therapies at admission. Renewed interest in the use of PD for AKI therapy has emerged due to its increasing use in low- and middle-income countries. In high-income countries, the coronavirus disease 2019 (COVID-19) pandemic, saw PD for AKI used early on, where many critical care units were in crisis and relied on PD use when resources for other AKI therapy modalities were limited. In this review, we highlight advantages and disadvantages of PD in critical care settings and indications and contraindications for its use. We provide an overview of literature to support both PD treatment during AKI and its continuation as a maintenance therapy during critical illness. For AKI therapy, we further discuss establishment of PD access, PD prescription management, and complication monitoring and treatment. Finally, we discuss expansion in the use of PD for AKI therapy extending beyond its role during times of resource constraints.

Cardiovascular morbidity and mortality occur with an extraordinarily high incidence in the hemodialysis-dependent end-stage kidney disease population. There is a clear need to improve identification of those individuals at the highest risk of cardiovascular complications in order to better target them for preventative therapies. Twelve-lead electrocardiograms are ubiquitous and use inexpensive technology that can be administered with minimal inconvenience to patients and at a minimal burden to care providers. The embedded waveforms encode significant information on the cardiovascular structure and function that might be unlocked and used to identify at-risk individuals with the use of artificial intelligence techniques like deep learning. In this review, we discuss the experience with deep learning-based analysis of electrocardiograms to identify cardiovascular abnormalities or risk and the potential to extend this to the setting of dialysis-dependent end-stage kidney disease.

BACKGROUND:Heart failure is the most common cardiovascular complication of chronic kidney disease (CKD) and foreshadows a high morbidity and mortality rate. Baroreflex impairment likely contributes to cardiovascular mortality. We aimed to study the associations between CKD, heart failure, and baroreflex sensitivity (BRS) and their association with cardiovascular outcomes. METHODS:) with BRS using iterative models. Cox proportional hazards models were used to assess associations of binary BRS and subgroups according to categorizations of CKD and BRS with cardiovascular mortality. RESULTS:=0.05). In regression models, CKD and BRS were independently associated. Cardiovascular mortality was significantly increased in individuals with or without CKD and depressed BRS compared with those with preserved BRS and CKD. CONCLUSIONS:Cardiac BRS is depressed in patients with mild to moderate CKD and HF and associated with cardiovascular mortality. Additional study to confirm its contribution to cardiovascular mortality, particularly in advanced CKD, is warranted.

BACKGROUND/UNASSIGNED:Bradycardia and asystole events are common among patients treated with maintenance hemodialysis. However, triggers of these events in patients on maintenance hemodialysis (HD), particularly during the long interdialytic period when these events cluster, are uncertain. METHODS/UNASSIGNED:The Monitoring in Dialysis Study (MiD) enrolled 66 patients on maintenance HD who were implanted with loop recorders and followed for 6 months. We analyzed associations of predialysis laboratory values with clinically significant bradyarrhythmia or asystole (CSBA) during the 12 hours before an HD session. Associations with CSBA were analyzed with mixed-effect models. Adjusted negative binomial mixed-effect regression was used to estimate incidence rate ratios (IRR) for CSBA. We additionally evaluated associations of CSBA at any time during follow-up with time-averaged dialytic and laboratory parameters and associations of peridialytic parameters with occurrence of CSBA from the start of one HD session to the beginning of the next. RESULTS/UNASSIGNED:=0.04). Use of dialysate sodium concentrations ≤135 (versus 140) mEq/L was associated with a reduced risk of CSBA from the start of one session to the beginning of next. CONCLUSIONS/UNASSIGNED:Although a few factors had modest associations with CSBA in some analyses, we did not identify any robust associations of modifiable parameters with CSBA in the MiD Study. Further investigation is needed to understand the high rates of arrhythmia in the hemodialysis population.

In patients with atrial fibrillation on dialysis, the incidence of stroke was similar with apixaban or no anticoagulation, regardless of P2Y12 prescription.In patients with atrial fibrillation on dialysis who were on a P2Y12 inhibitor, apixaban increased the risk of bleeding, compared with no anticoagulation.The incidence of myocardial infarction or ischemic stroke was similar with apixaban or no anticoagulation, regardless of P2Y12 prescription status.

BACKGROUND/UNASSIGNED:There has been a call by both patients and health professionals for the integration of palliative care with nephrology care, yet there is little evidence describing the effect of this approach. The objective of this paper is to report the feasibility and acceptability of a pilot randomized controlled trial testing the efficacy of integrated palliative and nephrology care. METHODS/UNASSIGNED:English speaking patients with CKD stage 5 were randomized to monthly palliative care visits for 3 months in addition to their usual care, as compared with usual nephrology care. Feasibility of recruitment, retention, completion of intervention processes, and feedback on participation was measured. Other outcomes included differences in symptom burden change, measured by the Integrated Palliative Outcome Scale-Renal, and change in quality of life, measured by the Kidney Disease Quality of Life questionnaire and completion of advance care planning documents. RESULTS/UNASSIGNED:Of the 67 patients approached, 45 (67%) provided informed consent. Of these, 27 patients completed the study (60%), and 14 (74%) of those in the intervention group completed all visits. We found small improvements in overall symptom burden (-2.92 versus 1.57) and physical symptom burden scores (-1.92 versus 1.79) in the intervention group. We did not see improvements in the quality-of-life scores, with the exception of the physical component score. The intervention group completed more advance care planning documents than controls (five health care proxy forms completed versus one, nine Medical Orders for Life Sustaining Treatment forms versus none). CONCLUSIONS/UNASSIGNED:We found that pilot testing through a randomized controlled trial of an ambulatory integrated palliative and nephrology care clinical program was feasible and acceptable to participants. This intervention has the potential to improve the disease experience for those with nondialysis CKD and should be tested in other CKD populations with longer follow-up. CLINICAL TRIALS REGISTRY NAME AND REGISTRATION NUMBER/UNASSIGNED:Pilot Randomized-controlled Trial of Integrated Palliative and Nephrology Care Versus Usual Nephrology Care, NCT04520984.