Teaching Conservative Kidney Management and Other Palliative Care Skills in Nephrology Fellowships.

Offering and providing effective conservative kidney management (CKM) for patients with end-stage kidney disease who do not want dialysis is a foundational skill that all nephrology fellows should learn during fellowship training. However, the current educational landscape in fellowship training programs is sparse and is not recognized currently as a skill within the Accreditation Council for Graduate Medical Education (ACGME) guidelines. Moreover, there is no standardized curriculum, methods of assessment of this learning objective, and no structure for implementation within general and subspecialty nephrology training programs. In this article, we discuss the current educational resources available for fellowship training programs, including interactive communication skills workshops such as NephroTalk, that address core concepts of CKM and assess communication skills and attitudes of trainees. Additional assessment tools should be prioritized when developing a CKM curriculum, including assessment of symptom management and medical knowledge acquisition. We propose that the ACGME nephrology milestones specifically highlight CKM as an important component within the ACGME nephrology milestones, thus ensuring that trainees understand how and when to offer CKM (knowledge), implement it effectively (skills), and conceptualize it as an appropriate course for patients in a number of varied situations (attitudes). We also outline a subspecialty pathway for palliative nephrology, to align with the recent American Society of Nephrology Task Force Recommendation to provide subspecialty training beyond core competencies, for those interested in pursuit of advanced training that ultimately can shape the CKM landscape in education and policy making.

Frequent vascular access thrombosis in a patient with end stage kidney disease on hemodialysis.

Vascular access thrombosis (VAT) is common among patients receiving hemodialysis and leads to missed dialysis treatments, hospitalizations, catheter placement, and graft/fistula abandonment. This article reviews the association between hypercoagulability and VAT and the high prevalence of hypercoagulable states in end-stage kidney disease (ESKD). This article reviews the role of antithrombotic and anticoagulant medications in preventing VAT. The article concludes by reviewing the unique challenges of using vitamin K antagonists in patients with ESKD.

Prone Positioning and Survival in Mechanically Ventilated Patients With Coronavirus Disease 2019-Related Respiratory Failure.

OBJECTIVES: Therapies for patients with respiratory failure from coronavirus disease 2019 are urgently needed. Early implementation of prone positioning ventilation improves survival in patients with acute respiratory distress syndrome, but studies examining the effect of proning on survival in patients with coronavirus disease 2019 are lacking. Our objective was to estimate the effect of early proning initiation on survival in patients with coronavirus disease 2019-associated respiratory failure. DESIGN: Data were derived from the Study of the Treatment and Outcomes in Critically Ill Patients with coronavirus disease 2019, a multicenter cohort study of critically ill adults with coronavirus disease 2019 admitted to 68 U.S. hospitals. Using these data, we emulated a target trial of prone positioning ventilation by categorizing mechanically ventilated hypoxemic (ratio of Pao2 over the corresponding Fio2 ≤ 200 mm Hg) patients as having been initiated on proning or not within 2 days of ICU admission. We fit an inverse probability-weighted Cox model to estimate the mortality hazard ratio for early proning versus no early proning. Patients were followed until death, hospital discharge, or end of follow-up. SETTING: ICUs at 68 U.S. sites. PATIENTS: Critically ill adults with laboratory-confirmed coronavirus disease 2019 receiving invasive mechanical ventilation with ratio of Pao2 over the corresponding Fio2 less than or equal to 200 mm Hg. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 2,338 eligible patients, 702 (30.0%) were proned within the first 2 days of ICU admission. After inverse probability weighting, baseline and severity of illness characteristics were well-balanced between groups. A total of 1,017 (43.5%) of the 2,338 patients were discharged alive, 1,101 (47.1%) died, and 220 (9.4%) were still hospitalized at last follow-up. Patients proned within the first 2 days of ICU admission had a lower adjusted risk of death compared with nonproned patients (hazard ratio, 0.84; 95% CI, 0.73-0.97). CONCLUSIONS: In-hospital mortality was lower in mechanically ventilated hypoxemic patients with coronavirus disease 2019 treated with early proning compared with patients whose treatment did not include early proning.

Extracorporeal membrane oxygenation in patients with severe respiratory failure from COVID-19.

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: We examined the clinical features and outcomes of 190 patients treated with ECMO within 14 days of ICU admission, using data from a multicenter cohort study of 5122 critically ill adults with COVID-19 admitted to 68 hospitals across the United States. To estimate the effect of ECMO on mortality, we emulated a target trial of ECMO receipt versus no ECMO receipt within 7 days of ICU admission among mechanically ventilated patients with severe hypoxemia (PaO2/FiO2 < 100). Patients were followed until hospital discharge, death, or a minimum of 60 days. We adjusted for confounding using a multivariable Cox model. RESULTS: Among the 190 patients treated with ECMO, the median age was 49 years (IQR 41-58), 137 (72.1%) were men, and the median PaO2/FiO2 prior to ECMO initiation was 72 (IQR 61-90). At 60 days, 63 patients (33.2%) had died, 94 (49.5%) were discharged, and 33 (17.4%) remained hospitalized. Among the 1297 patients eligible for the target trial emulation, 45 of the 130 (34.6%) who received ECMO died, and 553 of the 1167 (47.4%) who did not receive ECMO died. In the primary analysis, patients who received ECMO had lower mortality than those who did not (HR 0.55; 95% CI 0.41-0.74). Results were similar in a secondary analysis limited to patients with PaO2/FiO2 < 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.

Thrombosis, Bleeding, and the Observational Effect of Early Therapeutic Anticoagulation on Survival in Critically Ill Patients With COVID-19.

BACKGROUND: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival. DESIGN: In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used. SETTING: 67 hospitals in the United States. PARTICIPANTS: Adults with COVID-19 admitted to a participating ICU. MEASUREMENTS: Time to death, censored at hospital discharge, or date of last follow-up. RESULTS: Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35]). LIMITATION: Observational design. CONCLUSION: Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation. PRIMARY FUNDING SOURCE: None.

Risks and Options With Gadolinium-Based Contrast Agents in Patients With CKD: A Review.

Gadolinium-based contrast agents (GBCAs) improve the diagnostic capabilities of magnetic resonance imaging. Although initially believed to be without major adverse effects, GBCA use in patients with severe chronic kidney disease (CKD) was demonstrated to cause nephrogenic systemic fibrosis (NSF). Restrictive policies of GBCA use in CKD and selective use of GBCAs that bind free gadolinium more strongly have resulted in the virtual elimination of NSF cases. Contemporary studies of the use of GBCAs with high binding affinity for free gadolinium in severe CKD demonstrate an absence of NSF. Despite these observations and the limitations of contemporary studies, physicians remain concerned about GBCA use in severe CKD. Concerns of GBCA use in severe CKD are magnified by recent observations demonstrating gadolinium deposition in brain and a possible systemic syndrome attributed to GBCAs. Radiologic advances have resulted in several new imaging modalities that can be used in the severe CKD population and that do not require GBCA administration. In this article, we critically review GBCA use in patients with severe CKD and provide recommendations regarding GBCA use in this population.

AKI Treated with Renal Replacement Therapy in Critically Ill Patients with COVID-19.

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.

Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19.

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.

Factors Associated With Death in Critically Ill Patients With Coronavirus Disease 2019 in the US.

Importance: The US is currently an epicenter of the coronavirus disease 2019 (COVID-19) pandemic, yet few national data are available on patient characteristics, treatment, and outcomes of critical illness from COVID-19. Objectives: To assess factors associated with death and to examine interhospital variation in treatment and outcomes for patients with COVID-19. Design, Setting, and Participants: This multicenter cohort study assessed 2215 adults with laboratory-confirmed COVID-19 who were admitted to intensive care units (ICUs) at 65 hospitals across the US from March 4 to April 4, 2020. Exposures: Patient-level data, including demographics, comorbidities, and organ dysfunction, and hospital characteristics, including number of ICU beds. Main Outcomes and Measures: The primary outcome was 28-day in-hospital mortality. Multilevel logistic regression was used to evaluate factors associated with death and to examine interhospital variation in treatment and outcomes. Results: A total of 2215 patients (mean [SD] age, 60.5 [14.5] years; 1436 [64.8%] male; 1738 [78.5%] with at least 1 chronic comorbidity) were included in the study. At 28 days after ICU admission, 784 patients (35.4%) had died, 824 (37.2%) were discharged, and 607 (27.4%) remained hospitalized. At the end of study follow-up (median, 16 days; interquartile range, 8-28 days), 875 patients (39.5%) had died, 1203 (54.3%) were discharged, and 137 (6.2%) remained hospitalized. Factors independently associated with death included older age (≥80 vs <40 years of age: odds ratio [OR], 11.15; 95% CI, 6.19-20.06), male sex (OR, 1.50; 95% CI, 1.19-1.90), higher body mass index (≥40 vs <25: OR, 1.51; 95% CI, 1.01-2.25), coronary artery disease (OR, 1.47; 95% CI, 1.07-2.02), active cancer (OR, 2.15; 95% CI, 1.35-3.43), and the presence of hypoxemia (Pao2:Fio2<100 vs ≥300 mm Hg: OR, 2.94; 95% CI, 2.11-4.08), liver dysfunction (liver Sequential Organ Failure Assessment score of 2-4 vs 0: OR, 2.61; 95% CI, 1.30-5.25), and kidney dysfunction (renal Sequential Organ Failure Assessment score of 4 vs 0: OR, 2.43; 95% CI, 1.46-4.05) at ICU admission. Patients admitted to hospitals with fewer ICU beds had a higher risk of death (<50 vs ≥100 ICU beds: OR, 3.28; 95% CI, 2.16-4.99). Hospitals varied considerably in the risk-adjusted proportion of patients who died (range, 6.6%-80.8%) and in the percentage of patients who received hydroxychloroquine, tocilizumab, and other treatments and supportive therapies. Conclusions and Relevance: This study identified demographic, clinical, and hospital-level risk factors that may be associated with death in critically ill patients with COVID-19 and can facilitate the identification of medications and supportive therapies to improve outcomes.

Use of Dietary Supplements in Living Kidney Donors: A Critical Review.

Dietary supplement use is high among US adults, with the intention by users to promote overall health and wellness. Kidney donors, who are selected based on their overall good health and wellness, can have high utilization rates of dietary supplements. We provide a framework for the evaluation of living kidney donors and use of dietary supplements. In this review, dietary supplements will include any orally administered dietary or complementary nutritional products, but excluding micronutrients (vitamins and minerals), food, and cannabis. Use of dietary supplements can influence metabolic parameters that mask future risk for chronic illness such as diabetes and hypertension. Dietary supplements can also alter bleeding risk, anesthesia and analgesic efficacy, and safety in a perioperative period. Finally, postdonation monitoring of kidney function and risk for supplement-related nephrotoxicity should be part of a kidney donor educational process. For practitioners evaluating a potential kidney donor, we provide a list of the most commonly used herbal supplements and the effects on evaluation in a predonation, perioperative donation, and postoperative donation phase. Finally, we provide recommendations for best practices for integration into a comprehensive care plan for kidney donors during all stages of evaluation. We recommend avoidance of dietary supplements in a kidney donor population, although there is a paucity of data that identifies true harm. Rather, associations, known mechanisms of action, and common sense suggest that we avoid use in this population.

The Controversy of Contrast-Induced Nephropathy With Intravenous Contrast: What Is the Risk?

Contrast-induced nephropathy (CIN) has long been observed in both experimental and clinical studies. However, recent observational studies have questioned the prevalence and severity of CIN following intravenous contrast exposure. Initial studies of acute kidney injury following intravenous contrast were limited by the absence of control groups or contained control groups that did not adjust for additional acute kidney injury risk factors, including prevalent chronic kidney disease, as well as accepted prophylactic strategies. More contemporary use of propensity score-adjusted models have attempted to minimize the risk for selection bias, although bias cannot be completely eliminated without a prospective randomized trial. Based on existing data, we recommend the following CIN risk classification: patients with estimated glomerular filtration rates (eGFRs) ≥ 45mL/min/1.73m2 are at negligible risk for CIN, while patients with eGFRs<30mL/min/1.73m2 are at high risk for CIN. Patients with eGFRs between 30 and 44mL/min/1.73m2 are at an intermediate risk for CIN unless diabetes mellitus is present, which would further increase the risk. In all patients at any increased risk for CIN, the risk for CIN needs to be balanced by the risk of not performing an intravenous contrast-enhanced study.

Preoperative Risk Assessment and Management in Adults Receiving Maintenance Dialysis and Those With Earlier Stages of CKD.

With an increasingly aging population and improved mortality in individuals with end-stage kidney disease, more surgeries are being performed on patients with all stages of chronic kidney disease (CKD). This high-risk population carries unique risk factors that have been associated with increased adverse perioperative outcomes, including acute kidney injury, cardiovascular events, and mortality. In this article, we review the literature describing absolute risks associated with common surgeries performed in patients with CKD and patients receiving maintenance dialysis. We also review perioperative optimization with special risk assessment including evaluation of cardiovascular and bleeding risk evaluation, hypertension management, and timing of dialysis. Predictive model scores are reviewed as a method to stratify risk for acute kidney injury, major adverse cardiac events, or other serious complications with elective surgeries. A multidisciplinary approach with individualized counseling is necessary to counsel the patient with advanced CKD or patients treated with maintenance dialysis considering elective surgery.

Oral nutritional supplements and 30-day readmission rate in hypoalbuminemic maintenance hemodialysis patients.

INTRODUCTION: Hemodialysis (HD) patients are hospitalized nearly twice yearly, and 35% of these patients are rehospitalized within 30-days postdischarge. We hypothesized that monitored oral nutritional supplementation (ONS) during HD treatment may decrease readmissions. METHODS: A cohort of maintenance HD patients, treated at a large dialysis organization, who were hospitalized with a postdischarge albumin of ≤3.5 g/dL, without documented ONS use 90 days prior to the index hospitalization were identified. Individuals who received monitored intradialytic ONS postdischarge were compared to those without receipt of ONS. The outcome of interest was 30-day hospital readmissions. Logistic regression was used to assess the association between ONS receipt and 30-day readmission events, with adjustment for case-mix and laboratory variables. FINDINGS: Of 5479 eligible patients, ONS was prescribed to 1420 individuals. Mean age was 64.6 ± 14.1 (SD) years; median dialysis vintage was 3.9 years. There were 274 (19%) readmissions among ONS recipients vs. 1571 (38.7%) among controls during the 30-day follow-up period. Individuals who did not receive ONS had increased odds of readmission [OR 2.26 (95% CI 1.02, 2.53)] in 30 days, as compared to those who did receive ONS postdischarge. In sensitivity analyses using a propensity score matched cohort, the odds ratio of readmissions within 30 days postdischarge was 1.71 (95% CI: 1.42, 2.07) for individuals who did not receive ONS as compared to those who received ONS. DISCUSSION: Consumption of ONS during HD sessions is associated with reduced hospital readmission rates among in-center maintenance HD with severe hypoalbuminemia at 30 days post-hospital discharge.