A Framework for Antiracist Curriculum Changes in Nephrology Education.

Addressing persistent racial health disparities in cases of kidney disease will first require significant investment in examining how structural racism has influenced our clinical practice and medical education. Improving how we understand and articulate race is critical for achieving this goal. This work begins with ensuring that race's mention within nephrology literature and curricular materials for medical trainees is thoroughly rooted in evidence-based rationale-not to serve as a proxy for polygenic contributions, social determinants of health, or systemic health care barriers. While many institutions are increasingly recognizing the importance of instituting such changes on behalf of the systematically marginalized patient populations who are most affected by these disparities, there is a paucity of guidance on how to critically appraise and revise decades of pathophysiological and epidemiological findings through an antiracist lens. In this article, we propose an inquiry-based framework with case-study examples to help readers recognize improper use of race within nephrology, assess personal and institutional readiness to introduce changes to said content, and generate materials that center evidence-based findings and reject harmful misinterpretations of race.

An Innovative Approach for Integrating Mandatory, Longitudinal Spirituality Training Into the Medical School Curriculum.

PROBLEM: Most Americans indicate they are religious and/or spiritual and wish to have their beliefs taken into account when engaging with health care providers, yet gaps in medical education and health care practice remain. To underscore the importance of spirituality as a significant social determinant of health, a team at the Icahn School of Medicine at Mount Sinai in New York developed mandatory spirituality and health training for students integrated into all 4 years of the undergraduate medical education curriculum. APPROACH: From 2014 to 2020, a small group of faculty took an innovative approach, launching the initiative and expanding the team by engaging interprofessional faculty and staff from across the institution. The team used an iterative process to integrate 4 distinct modules into 4 existing courses, spanning the 4 years of medical school. OUTCOMES: The majority of students found that the spirituality and health curriculum was valuable to training and professional development. They appreciated the importance of patients' spiritual needs, valued learning about the role chaplains play in patient care and how to initiate a consult, and indicated they intended to integrate spiritual history taking in their patient care. With respect to process, 3 key factors-establishing an interprofessional team, working through an iterative process, and integrating the curriculum into existing courses-were critical to designing and implementing the modules. NEXT STEPS: The team aims to expand and improve the curriculum by linking learning to specific standardized competencies as well as developing more specific performance assessments to demonstrate achievement of competencies. Professional development efforts will be enhanced so faculty can better model and reinforce the integration of spirituality into health care practices and expand the curriculum on spirituality and health into graduate medical education.

Acute Kidney Injury in Hospitalized Patients with COVID-19.

IMPORTANCE: Preliminary reports indicate that acute kidney injury (AKI) is common in coronavirus disease (COVID)-19 patients and is associated with worse outcomes. AKI in hospitalized COVID-19 patients in the United States is not well-described. OBJECTIVE: To provide information about frequency, outcomes and recovery associated with AKI and dialysis in hospitalized COVID-19 patients. DESIGN: Observational, retrospective study. SETTING: Admitted to hospital between February 27 and April 15, 2020. PARTICIPANTS: Patients aged ≥18 years with laboratory confirmed COVID-19 Exposures: AKI (peak serum creatinine increase of 0.3 mg/dL or 50% above baseline). Main Outcomes and Measures: Frequency of AKI and dialysis requirement, AKI recovery, and adjusted odds ratios (aOR) with mortality. We also trained and tested a machine learning model for predicting dialysis requirement with independent validation. RESULTS: A total of 3,235 hospitalized patients were diagnosed with COVID-19. AKI occurred in 1406 (46%) patients overall and 280 (20%) with AKI required renal replacement therapy. The incidence of AKI (admission plus new cases) in patients admitted to the intensive care unit was 68% (553 of 815). In the entire cohort, the proportion with stages 1, 2, and 3 AKI were 35%, 20%, 45%, respectively. In those needing intensive care, the respective proportions were 20%, 17%, 63%, and 34% received acute renal replacement therapy. Independent predictors of severe AKI were chronic kidney disease, systolic blood pressure, and potassium at baseline. In-hospital mortality in patients with AKI was 41% overall and 52% in intensive care. The aOR for mortality associated with AKI was 9.6 (95% CI 7.4-12.3) overall and 20.9 (95% CI 11.7-37.3) in patients receiving intensive care. 56% of patients with AKI who were discharged alive recovered kidney function back to baseline. The area under the curve (AUC) for the machine learned predictive model using baseline features for dialysis requirement was 0.79 in a validation test. CONCLUSIONS AND RELEVANCE: AKI is common in patients hospitalized with COVID-19, associated with worse mortality, and the majority of patients that survive do not recover kidney function. A machine-learned model using admission features had good performance for dialysis prediction and could be used for resource allocation.

Radiocontrast Toxicity.

Intravenous and intraarterial contrast media are invaluable tools in the diagnosis of anatomic lesions. However, they have been associated with deleterious renal events, ranging from acute kidney injury (iodinated contrast) to nephrogenic systemic fibrosis (gadolinium-containing agents). Contrast-associated acute kidney injury has a wide incidence, likely due to differences in populations studied, with incidence likely overstated due to comorbid conditions at the time of contrast exposure. Pathophysiology includes hemodynamic and direct toxic effects. Preventative strategies include intravenous saline administration, higher urine pH, and statin administration. Importantly, because of fears of contrast-associated acute kidney injury, practitioners may be selecting only the healthiest patients for contrast exposure. Gadolinium-based contrast agents may cause their toxicity through being unbound from their ligand, and certain preparations may be less harmful than others.

Use of an iPad App to simulate pressure-volume loops and cardiovascular physiology.

The purpose of this laboratory exercise is to model the changes in preload, afterload, and contractility on a simulated pressure-volume loop and to correlate those findings with common measurements of clinical cardiovascular physiology. Once students have modeled these changes on a healthy heart, the students are asked to look at a simulated case of cardiogenic shock. Effects on preload, contractility, and afterload are explored, as well as the hemodynamic effects of a number of student-suggested treatment strategies.

Effect of cholecalciferol supplementation on inflammation and cellular alloimmunity in hemodialysis patients: data from a randomized controlled pilot trial.

BACKGROUND: Memory T-cells are mediators of transplant injury, and no therapy is known to prevent the development of cross-reactive memory alloimmunity. Activated vitamin D is immunomodulatory, and vitamin D deficiency, common in hemodialysis patients awaiting transplantation, is associated with a heightened alloimmune response. Thus, we tested the hypothesis that vitamin D3 supplementation would prevent alloreactive T-cell memory formation in vitamin D-deficient hemodialysis patients. METHODS AND FINDINGS: We performed a 12-month single-center pilot randomized, controlled trial of 50,000 IU/week of cholecalciferol (D3) versus no supplementation in 96 hemodialysis patients with serum 25(OH)D<25 ng/mL, measuring effects on serum 25(OH)D and phenotypic and functional properties of T-cells. Participants were randomized 2:1 to active treatment versus control. D3 supplementation increased serum 25(OH)D at 6 weeks (13.5 [11.2] ng/mL to 42.5 [18.5] ng/mL, p<0.001) and for the duration of the study. No episodes of sustained hypercalcemia occurred in either group. Results of IFNγ ELISPOT-based panel of reactive T-cell assays (PRT), quantifying alloreactive memory, demonstrated greater increases in the controls over 1 year compared to the treatment group (delta PRT in treatment 104.8+/-330.8 vs 252.9+/-431.3 in control), but these changes in PRT between groups did not reach statistical significance (p = 0.25). CONCLUSIONS: D3 supplements are safe, effective at treating vitamin D deficiency, and may prevent time-dependent increases in T-cell alloimmunity in hemodialysis patients, but their effects on alloimmunity need to be confirmed in larger studies. These findings support the routine supplementation of vitamin D-deficient transplant candidates on hemodialysis and highlight the need for large-scale prospective studies of vitamin D supplementation in transplant candidates and recipients. TRIAL REGISTRATION: Clinicaltrials.gov NCT01175798.

Complement regulates CD4 T-cell help to CD8 T cells required for murine allograft rejection.

Although induction of CD8 T-cell responses to transplants requires CD4-cell help, how this help is transmitted remains incompletely characterized. In vitro, cognate interactions between CD4 T cells and dendritic cells (DCs) induce C3a and C5a production. CD8(+) T cells lacking C3a receptor (C3aR) and C5a receptor (C5aR) proliferate weakly to allogeneic DCs despite CD4 help, indicating that CD4-cell help is mediated, in part, through DC-derived C3a/C5a acting on CD8(+) T cell-expressed C3aR/C5aR. In support of this concept, augmenting DC C5a/C3a production bypasses the requirement for CD4- and CD40-dependent help to wild-type CD8(+) T cells. CD4-deficient recipients of allogeneic heart transplants prime weak CD8 responses and do not acutely reject their grafts. In contrast, CD4-deficient chimeric mice possessing decay accelerating factor deficient (Daf1(-/-)) bone marrow, in which DC C3a/C5a production is potentiated, acutely reject transplants through a CD8 cell-dependent mechanism. Furthermore, hearts transplanted into CD40(-/-) mice prime weak CD8-cell responses and survive indefinitely, but hearts transplanted into Daf1(-/-)CD40(-/-) recipients undergo CD8 cell-dependent rejection. Together, the data indicate that heightened production and activation of immune cell-derived complement bypasses the need for CD40/CD154 interactions and implicate antigen-presenting cell-produced C5a and C3a as molecular bridges linking CD4 help to CD8(+) T cells.

Donor deficiency of decay-accelerating factor accelerates murine T cell-mediated cardiac allograft rejection.

Decay-accelerating factor (DAF) is a cell surface regulator that accelerates the dissociation of C3/C5 convertases and thereby prevents the amplification of complement activation on self cells. In the context of transplantation, DAF has been thought to primarily regulate antibody-mediated allograft injury, which is in part serum complement-dependent. Based on our previously delineated link between DAF and CD4 T cell responses, we evaluated the effects of donor Daf1 (the murine homolog of human DAF) deficiency on CD8 T cell-mediated cardiac allograft rejection. MHC-disparate Daf1(-/-) allografts were rejected with accelerated kinetics compared with wild-type grafts. The accelerated rejection predominantly tracked with DAF's absence on bone marrow-derived cells in the graft and required allograft production of C3. Transplantation of Daf1(-/-) hearts into wild-type allogeneic hosts augmented the strength of the anti-donor (direct pathway) T cell response, in part through complement-dependent proliferative and pro-survival effects on alloreactive CD8 T cells. The accelerated allograft rejection of Daf1(-/-) hearts occurred in recipients lacking anti-donor Abs. The results reveal that donor DAF expression, by controlling local complement activation on interacting T cell APC partners, regulates the strength of the direct alloreactive CD8(+) T cell response. The findings provide new insights into links between innate and adaptive immunity that could be exploited to limit T cell-mediated injury to an allograft following transplantation.