Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:The kidney protective effects of renin-angiotensin system inhibitors are greater in people with higher levels of albuminuria at treatment initiation. Whether this applies to sodium-glucose cotransporter 2 (SGLT2) inhibitors is uncertain, particularly in patients with a very high urine albumin-to-creatinine ratio (UACR; ≥3000 mg/g). We examined the association between baseline UACR and the effects of the SGLT2 inhibitor, canagliflozin, on efficacy and safety outcomes in the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) randomized controlled trial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:=506). In addition, we examined the effects of canagliflozin on UACR itself, eGFR slope, and the intermediate outcomes of glycated hemoglobin, body weight, and systolic BP. RESULTS:=0.02). Rates of kidney-related adverse events were lower with canagliflozin, with a greater relative reduction in higher UACR categories. CONCLUSIONS:Canagliflozin safely reduces kidney and cardiovascular events in people with type 2 diabetes and severely increased albuminuria. In this population, the relative kidney benefits were consistent over a range of albuminuria levels, with greatest absolute kidney benefit in those with an UACR ≥3000 mg/g. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER/UNASSIGNED:ClinicalTrials.gov: CREDENCE, NCT02065791. PODCAST/UNASSIGNED:This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_02_22_CJN15260920_final.mp3.

PURPOSE OF REVIEW/OBJECTIVE:Several nontraditional risk factors have been the focus of research in an attempt to understand the disproportionately high cardiovascular morbidity and mortality in chronic kidney disease (CKD) and end-stage kidney disease (ESKD) populations. One such category of risk factors is cardiovascular autonomic dysfunction. Its true prevalence in the CKD/ESKD population is unknown but existing evidence suggests it is common. Due to lack of standardized diagnostic and treatment options, this condition remains undiagnosed and untreated in many patients. In this review, we discuss current evidence pointing toward the role of autonomic nervous system (ANS) dysfunction in CKD, building off of crucial historical evidence and thereby highlighting the areas in need for future research interest. RECENT FINDINGS/RESULTS:There are several key mediators and pathways leading to cardiovascular autonomic dysfunction in CKD and ESKD. We review studies exploring the mechanisms involved and discuss the current measurement tools and indices to evaluate the ANS and their pitfalls. There is a strong line of evidence establishing the temporal sequence of worsening autonomic function and kidney function and vice versa. Evidence linking ANS dysfunction and arrhythmia, sudden cardiac death, intradialytic hypotension, heart failure and hypertension are discussed. SUMMARY/CONCLUSIONS:There is a need for early recognition and referral of CKD and ESKD patients suspected of cardiovascular ANS dysfunction to prevent the downstream effects described in this review.There are many unknowns in this area and a clear need for further research.

PURPOSE:Limited data are available on venovenous extracorporeal membrane oxygenation (ECMO) in patients with severe hypoxemic respiratory failure from coronavirus disease 2019 (COVID-19). METHODS: < 100). Patients were followed until hospital discharge, death, or a minimum of 60 days. We adjusted for confounding using a multivariable Cox model. RESULTS: < 80 (HR 0.55; 95% CI 0.40-0.77). CONCLUSION:In select patients with severe respiratory failure from COVID-19, ECMO may reduce mortality.

OBJECTIVES/UNASSIGNED:The ideal clinical model to deliver palliative care to patients with advanced kidney disease is currently unknown. Internationally, ambulatory kidney palliative care clinics have emerged with positive outcomes, yet there is limited data from the United States (US). In this exploratory study we report perceptions of a US-based ambulatory kidney palliative care clinic from the perspective of patient and caregiver attendees. The objective of this study was to inform further improvement of our clinical program. METHODS/UNASSIGNED:Semi-structured interviews were conducted to elicit the patient and caregiver experience. Eleven interviews (8 patients with chronic kidney disease stage IV or V and 3 caregivers) were analyzed using qualitative description design. RESULTS/UNASSIGNED:We identified 2 themes: "Communication addressing the emotional and physical aspects of disease" and "Filling gaps in care"; Subthemes include perceived value in symptom management, assistance with coping with disease, engagement in advance care planning, program satisfaction and patient activation. SIGNIFICANCE OF RESULTS/UNASSIGNED:Qualitative analysis showed that attendees of an ambulatory kidney palliative care clinic found the clinic enhanced the management of their kidney disease and provided services that filled current gaps in their care. Shared experiences highlight the significant challenges of life with kidney disease and the possible benefits of palliative care for this population. Further study to determine the optimal model of care for kidney palliative care is needed. Inclusion of the patient and caregiver perspective will be essential in this development.

Importance:Therapies that improve survival in critically ill patients with coronavirus disease 2019 (COVID-19) are needed. Tocilizumab, a monoclonal antibody against the interleukin 6 receptor, may counteract the inflammatory cytokine release syndrome in patients with severe COVID-19 illness. Objective:To test whether tocilizumab decreases mortality in this population. Design, Setting, and Participants:The data for this study were derived from a multicenter cohort study of 4485 adults with COVID-19 admitted to participating intensive care units (ICUs) at 68 hospitals across the US from March 4 to May 10, 2020. Critically ill adults with COVID-19 were categorized according to whether they received or did not receive tocilizumab in the first 2 days of admission to the ICU. Data were collected retrospectively until June 12, 2020. A Cox regression model with inverse probability weighting was used to adjust for confounding. Exposures:Treatment with tocilizumab in the first 2 days of ICU admission. Main Outcomes and Measures:Time to death, compared via hazard ratios (HRs), and 30-day mortality, compared via risk differences. Results:Among the 3924 patients included in the analysis (2464 male [62.8%]; median age, 62 [interquartile range {IQR}, 52-71] years), 433 (11.0%) received tocilizumab in the first 2 days of ICU admission. Patients treated with tocilizumab were younger (median age, 58 [IQR, 48-65] vs 63 [IQR, 52-72] years) and had a higher prevalence of hypoxemia on ICU admission (205 of 433 [47.3%] vs 1322 of 3491 [37.9%] with mechanical ventilation and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of <200 mm Hg) than patients not treated with tocilizumab. After applying inverse probability weighting, baseline and severity-of-illness characteristics were well balanced between groups. A total of 1544 patients (39.3%) died, including 125 (28.9%) treated with tocilizumab and 1419 (40.6%) not treated with tocilizumab. In the primary analysis, during a median follow-up of 27 (IQR, 14-37) days, patients treated with tocilizumab had a lower risk of death compared with those not treated with tocilizumab (HR, 0.71; 95% CI, 0.56-0.92). The estimated 30-day mortality was 27.5% (95% CI, 21.2%-33.8%) in the tocilizumab-treated patients and 37.1% (95% CI, 35.5%-38.7%) in the non-tocilizumab-treated patients (risk difference, 9.6%; 95% CI, 3.1%-16.0%). Conclusions and Relevance:Among critically ill patients with COVID-19 in this cohort study, the risk of in-hospital mortality in this study was lower in patients treated with tocilizumab in the first 2 days of ICU admission compared with patients whose treatment did not include early use of tocilizumab. However, the findings may be susceptible to unmeasured confounding, and further research from randomized clinical trials is needed.

BACKGROUND:AKI is a common sequela of coronavirus disease 2019 (COVID-19). However, few studies have focused on AKI treated with RRT (AKI-RRT). METHODS:We conducted a multicenter cohort study of 3099 critically ill adults with COVID-19 admitted to intensive care units (ICUs) at 67 hospitals across the United States. We used multivariable logistic regression to identify patient-and hospital-level risk factors for AKI-RRT and to examine risk factors for 28-day mortality among such patients. RESULTS:A total of 637 of 3099 patients (20.6%) developed AKI-RRT within 14 days of ICU admission, 350 of whom (54.9%) died within 28 days of ICU admission. Patient-level risk factors for AKI-RRT included CKD, men, non-White race, hypertension, diabetes mellitus, higher body mass index, higher d-dimer, and greater severity of hypoxemia on ICU admission. Predictors of 28-day mortality in patients with AKI-RRT were older age, severe oliguria, and admission to a hospital with fewer ICU beds or one with greater regional density of COVID-19. At the end of a median follow-up of 17 days (range, 1-123 days), 403 of the 637 patients (63.3%) with AKI-RRT had died, 216 (33.9%) were discharged, and 18 (2.8%) remained hospitalized. Of the 216 patients discharged, 73 (33.8%) remained RRT dependent at discharge, and 39 (18.1%) remained RRT dependent 60 days after ICU admission. CONCLUSIONS:AKI-RRT is common among critically ill patients with COVID-19 and is associated with a hospital mortality rate of >60%. Among those who survive to discharge, one in three still depends on RRT at discharge, and one in six remains RRT dependent 60 days after ICU admission.

Introduction/UNASSIGNED:Establishing the frequency and nature of arrhythmias in hemodialysis (HD) is an important step in improving outcomes of these patients. We undertook this systematic review and meta-analysis to characterize arrhythmia frequency in maintenance HD patients. Methods/UNASSIGNED:statistic was used to quantify heterogeneity. Results/UNASSIGNED: < 0.001) than the rate of bradycardia/asystole reported in the same patients. Incidence of atrial fibrillation (AF) varied significantly across the studies (from 0.07 to 0.83 patients per year) reflecting variable definitions (new-onset vs. total number of episodes). Conclusion/UNASSIGNED:The incidence of arrhythmias among chronic HD patients is high, with bradycardia/asystole occurring more frequently than ventricular arrhythmias. Additional studies to refine estimates particularly of AF are needed.

Background: Left ventricular (LV) systolic dysfunction is common in patients on maintenance hemodialysis (HD). Early identification of patients with depressed left ventricular ejection fraction (LVEF) can facilitate disease modifying treatment. Electrocardiograms (ECGs) are routinely performed in patients on HD, however they have not been used for estimating LVEF in this population.
Method(s): We analyzed data from five Mount Sinai facilities. Patients on HD with a transthoracic echocardiogram within 7 days of an ECG were identified using diagnostic and procedure codes. ECG data were preprocessed to remove recording artifacts, plotted to an image, and along with patient demographics were analyzed using a model comprised of a Multi-Layer Perceptron and a Convolutional Neural Network. We developed three models; 1) trained from scratch in only HD patients, 2) pre-trained on natural images (Imagenet), and 3) pre-trained on all LVEF:ECG pairs (n=696,890) excluding those for ESRD patients. Models 2 and 3 leverage transfer learning, which reuses knowledge gained from a task to perform a similar task. All models were trained/tested on LVEF:ECG pairs for ESRD patients within a Group Stratified K Fold (K=5) Cross Validation design, and performance was compared per Area Under Receiver Operating Characteristic curve (AUROC) for each category of LVEF, <=40%, 41 to <=50%, and >50%.
Result(s): We extracted 18,626 LVEF:ECG pairs for 2,168 ESRD patients. For detection of LVEF <=40%, models trained from scratch and pre-trained on Imagenet had AUROCs of 0.74 (95% CI: 0.67-0.80) and 0.71 (95% CI: 0.65-0.77) respectively. These were outperformed by the model pre-trained on ECG data [AUROC of 0.91 (95% CI: 0.88-0.93)]. Similar results were seen at detection of LVEF 41 to <=50% with the AUROC being 0.55 (95% CI: 0.49-0.6) for both the model trained from scratch and the Imagenet model, while the model pre-trained on ECG data achieved an AUROC of 0.82 (95% CI: 0.78-0.87).
Conclusion(s): A model pre-trained on non-HD LVEF:ECG pairs using transfer learning consistently outperformed models trained from scratch or pre-trained on Imagenet. This model can facilitate identification of LV systolic dysfunction in patients on HD. ROC curves

Background: Conservative kidney management (CKM) of kidney failure is an important treatment option for many patients. However, its availability in the United States (US) is not well described. We describe CKM resources and provider practice patterns in US Chronic Kidney Disease (CKD) clinics.
Method(s): Cross sectional analysis of provider surveys (n=22) from unique clinics in the US from the CKD Outcomes and Practice Patterns Study (CKDopps) collected between 2014-2017.
Result(s): Only eight (36%) providers reported involving palliative care in planning for and educating patients about kidney failure. A majority (59%) were extremely comfortable discussing CKM and nearly 100% typically discussed CKM as a treatment option. Nearly all (95%) reported their clinics had the ability to routinely deliver CKM, but only one had a CKM protocol or guideline, and none offered a specific CKM clinic. Most providers said their clinics used the word conservative to describe CKM, with 24% choosing palliative or supportive terminology. Regardless of involvement of PC, most providers estimated that 5% of their patients with or approaching kidney failure were managed with CKM. Patient preference, functional status, frailty, and comorbidities were the most important factors influencing provider decisions in contemplating the suitability of CKM for patients. (Figure 1)
Conclusion(s): Most providers report feeling comfortable discussing CKM, yet almost no clinics report resources or dedicated infrastructure for CKM delivery. Despite reported high frequency of discussing CKM, few patients were described as choosing this treatment pathway. Factors that influence consideration of CKM are consistent with elements that generally influence well-informed geriatric and end-of-life care. Efforts to improve assessment of those elements may allow for more informed recommendations of CKM

Background: Obesity is more prevalent among minorities, increasing the risk for cardio-renal morbidity. We explored interactions between race, body mass index (BMI), and the risk of hyperfiltration associated with Obesity Related Glomerulopathy (ORG).
Method(s): We created a cohort of women and girls ages 12-21 from the New York area using their longitudinal electronic health records (EHR). Glomerular filtration rate (GFR) was estimated in two ways: I) using the standard age recommended formulae, and II) eGFRr -without a race-specific coefficient. Multivariate logistic regression was used to analyze the relative contribution of risk factors for ORG associated hyperfiltration, defined by a threshold of >=135ml/min/1.73m2.
Result(s): 7315 Black and 15,102 non-Black women and girls were evaluated for kidney function in parallel to body measures. Hyperfiltration was more frequent in Black compared to non-Black individuals when using standard eGFR but was lower after eliminating the race-specific coefficient. Black race was independently associated with hyperfiltration with standard eGFR calculation (OR=3.43, 95% CI 2.95-3.99) but the association was reversed when estimated by eGFRr (OR=0.56, 95% CI 0.45-0.70). Risk of hyperfiltration was higher for Black individuals across all BMI strata with standard eGFR estimates, but when estimated as eGFRr hyperfiltration filtration risk was reduced for overweight (OR =0.70 95% CI 0.54-0.89) and obese (OR=0.47, 95% CI 0.37-0.60) participants.
Conclusion(s): Estimated CKD prevalence among Black adolescents and young adults increases following removal of the race coefficient while fewer have evidence of obesity associated hyperfiltration. In the CKD range of GFR we should consider a gradual increase in the race coefficient to avoid underestimation of obesity related glomerulopathy in the high normal range of GFR