TREX1 Mutation Causing Autosomal Dominant Thrombotic Microangiopathy and CKD-A Novel Presentation.

Renal thrombotic microangiopathy (TMA) involves diverse causes and clinical presentations. Genetic determinants causing alternate pathway complement dysregulation underlie a substantial proportion of cases. In a significant proportion of TMAs, no defect in complement regulation is identified. Mutations in the major mammalian 3' DNA repair exonuclease 1 (TREX1) have been associated with autoimmune and cerebroretinal vasculopathy syndromes. Carboxy-terminal TREX1 mutations that result in only altered localization of the exonuclease protein with preserved catalytic function cause microangiopathy of the brain and retina, termed retinal vasculopathy and cerebral leukodystrophy (RVCL). Kidney involvement reported with RVCL usually accompanies significant brain and retinal microangiopathy. We present a pedigree with autosomal dominant renal TMA and chronic kidney disease found to have a carboxy-terminal frameshift TREX1 variant. Although symptomatic brain and retinal microangiopathy is known to associate with carboxy-terminal TREX1 mutations, this report describes a carboxy-terminal TREX1 frameshift variant causing predominant renal TMA. These findings underscore the clinical importance of recognizing TREX1 mutations as a cause of renal TMA. This case demonstrates the value of whole-exome sequencing in unsolved TMA.

Implementing and Evaluating a Four-Year Integrated End-of-Life Care Curriculum for Medical Students.

PROBLEM: Meeting the needs of patients with life-limiting and terminal illness requires effectively trained physicians in all specialties to provide skillful and compassionate care. Despite mandates for end-of-life (EoL) care education, graduating medical students do not consistently feel prepared to provide this care. INTERVENTION: We have developed a longitudinal, integrated, and developmental 4-year curriculum in EoL care. The curriculum's purpose is to teach basic competencies in EoL care. A variety of teaching strategies emphasize experiential, skill-building activities with special attention to student self-reflection. In addition, we have incorporated interprofessional learning and education on the spiritual and cultural aspects of care. We created blended learning strategies combining interactive online modules with live workshops that promote flexibility, adaptability, and interprofessional learning opportunities. CONTEXT: The curriculum was implemented and evaluated in the 4-year program of studies at Yale School of Medicine. OUTCOME: A mixed-method evaluation of the curriculum included reviews of student written reflections and questionnaires, graduating student surveys, and demonstration of 4th-year students' competency in palliative care with an observed structured clinical examination (OSCE). These evaluations demonstrate significant improvements in students' self-reported preparedness in EoL care and perceptions of the adequacy in their instruction in EoL and palliative care, as well as competency in primary palliative care in a newly developed OSCE. LESSONS LEARNED: A 4-year longitudinal integrated curriculum enhances students' skills and preparedness in important aspects of EoL care. As faculty resources, clinical sites, and curricular structure vary by institution, proven and adaptable educational strategies as described in this article may be useful to address the mandate to improve EoL care education. Teaching strategies and curricular components and design as just described can be adapted to other programs.

Opting out: confidentiality and availability of an 'alibi' for potential living kidney donors in the USA.

Ethicists and guidelines have suggested that potential living kidney donors who withdraw from evaluation be offered an 'alibi.' We sought to determine what potential living kidney donors are told about their ability to opt out, alibi availability and postwithdrawal confidentiality. We reviewed 148 consent forms for living kidney donor evaluation from US transplant centres that performed >5 living kidney transplants in 2010-2011 (response rate 87%). We found that while 98% of centres used evaluation consent forms that indicated that the donor could withdraw, only 21% of these documents offered an alibi. Another 23% of centres' consent forms indicated that the transplant team would be willing to inform the intended recipient that an individual was not a potential donor. Relatively few consent documents explicitly addressed the confidentiality of the donor's health information (31%), candidacy status (18%), decision (24%) or reasons (23%) following withdrawal. To preserve potential donors' autonomy and relationships, we advocate that all transplant centres offer general alibis in their evaluation consent forms. We conclude by offering recommendations for evaluation consent discussions of opting out, alibis and postwithdrawal confidentiality.

A one-day centralized work-up for kidney transplant recipient candidates: a quality improvement report.

BACKGROUND: Waiting time for a kidney transplant is calculated from the date the patient is placed on the UNOS (United Network for Organ Sharing) waitlist to the date the patient undergoes transplant. Time from transplant evaluation to listing represents unaccounted waiting time, potentially resulting in longer dialysis exposure for some patients with prolonged evaluation times. There are established disparities demonstrating that groups of patients take longer to be placed on the waitlist and thus have less access to kidney transplant. STUDY DESIGN: Quality improvement report. SETTING & PARTICIPANTS: 905 patients from a university-based hospital were evaluated for kidney transplant candidacy, and analysis was performed from July 1, 2004, to January 31, 2010. QUALITY IMPROVEMENT PLAN: A 1-day centralized work-up was implemented on July 1, 2007, whereby the transplant center coordinated the necessary tests needed to fulfill minimal listing criteria. OUTCOME: Time from evaluation to UNOS listing was compared between the 2 cohorts. Multivariable Cox proportional hazards models were created to assess the relative hazards of waitlist placement comparing 1-day versus conventional work-up and were adjusted for age, sex, race, and education. RESULTS: Of 905 patients analyzed, 378 underwent conventional evaluation and 527 underwent a 1-day center-coordinated evaluation. Median time to listing in the 1-day center-coordinated evaluation compared with conventional was significantly less (46 vs 226 days, P < 0.001). On multivariable analysis controlling for age, sex, and education level, the 1-day in-center group was 3 times more likely to place patients on the wait list (adjusted HR, 3.08; 95% CI, 2.64-3.59). Listing time was significantly decreased across race, sex, education, and ethnicity. LIMITATIONS: Single center, retrospective. Variables that may influence transplant practitioners, such as comorbid conditions or functional status, were not assessed. CONCLUSIONS: A 1-day center-coordinated pretransplant work-up model significantly decreased time to listing for kidney transplant.

Medical Student Patient Outreach to Ensure Continuity of Care During the COVID-19 Pandemic.

Background: In response to the COVID-19 pandemic, the Yale New Haven Health System began rescheduling nonurgent outpatient appointments as virtual visits in March 2020. While Yale New Haven Health expanded its telemedicine infrastructure to accommodate this shift, many appointments were delayed and patients faced considerable uncertainty. Objective: Medical students created the Medical Student Task Force (MSTF) to help ensure continuity of care by calling patients whose appointments were delayed during this transition to telemedicine. Methods: Eighty-five student volunteers called 3765 internal medicine patients with canceled appointments, completing screening for 2197 patients. Volunteers screened for health care needs, assessed preferences for future appointments, and offered emotional support and information about COVID-19. Urgent or emergent patient concerns were triaged and escalated to providers. In this analysis, we used a mixed-methods approach: call information and provider responses were analyzed quantitatively, and patient feedback was analyzed qualitatively via thematic analysis. Results: Ninety-one percent of patients screened found the MSTF calls helpful. Twenty-one percent of patients reported health concerns, with 1% reporting urgent concerns escalated to and addressed by providers. Themes of patient comments included gratitude for outreach and social contact, utility of calls, and well-wishes for health care workers. Conclusions: By calling patients whose appointments had been canceled during a rapid transition to telemedicine, the MSTF helped bridge a potential gap in care by offering patients communication with their care teams, information, and support. We propose that this model could be used in other care systems urgently transitioning to outpatient telemedicine, whether during ongoing outbreaks of COVID-19 or other public health emergencies.

KDOQI US commentary on the 2009 KDIGO clinical practice guideline for the care of kidney transplant recipients.

In response to recently published KDIGO (Kidney Disease: Improving Global Outcomes) guidelines for the care of kidney transplant recipients (KTRs), the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) organized a working group of transplant nephrologists and surgeons to review these guidelines and comment on their relevance and applicability for US KTRs. The following commentaries on the KDIGO guidelines represent the consensus of our work group. The KDIGO transplant guidelines concentrated on aspects of transplant care most important to this population in the posttransplant period, such as immunosuppression, infection, malignancy, and cardiovascular care. Our KDOQI work group concurred with many of the KDIGO recommendations except in some important areas related to immunosuppression, in which decisions in the United States are largely made by transplant centers and are dependent in part on the specific patient population served. Most, but not all, KDIGO guidelines are relevant to US patients. However, implementation of many may remain a major challenge because of issues of limitation in resources needed to assist in the tasks of educating, counseling, and implementing and maintaining lifestyle changes. Although very few of the guidelines are based on evidence that is strong enough to justify their being used as the basis of policy or performance measures, they offer an excellent road map to navigate the complex care of KTRs.

HCV response in patients with end stage renal disease treated with combination pegylated interferon alpha-2a and ribavirin.

GOALS: To determine the efficacy and safety of combination therapy in patients with hepatitis C virus (HCV) and end-stage renal disease (ESRD). BACKGROUND: There is little data on the treatment of ESRD patients with pegylated interferon and ribavirin. We designed a pilot study to determine the initial and 12-week posttreatment viral response. STUDY: A nonrandomized, prospective observational study of adjusted-dose combination therapy. Twenty patients were enrolled and began pegylated interferon at 135 microg/wk SC, and 4 weeks later ribavirin was started at 200 mg PO weekly, increasing gradually to 3 times a week for a total of 48 weeks. RESULTS: Twenty patients: M:F 18:2; mean age 52.4 years; genotype 1: 18, non-genotype 1: 2. Of the 20 patients, 5 withdrew before starting treatment. Of the 11 patients who reached 3 months, 6 had early virologic response, defined as at least a 2-log drop in their HCV count (54.5%). Of the 5 patients who were treated for 1-year, only 1 patient had a response 12 weeks after treatment. Side effects included 4 cases of anemia and 1 patient with headache. CONCLUSIONS: The initial response rate in individuals taking 3 months of treatment in our study is comparable with studies in non-ESRD patients with no serious adverse side effects. However, the sustained posttreatment rate was low. This demonstrates that combination therapy is a safe therapeutic option in the ESRD population with HCV infection which needs further testing to determine if increasing the length of treatment and/or the dose of ribavirin will affect posttreatment rates.

Development and implementation of an innovative ward-based program to help medical students acquire end-of-life care experience.

The authors developed and implemented a new ward-based end-of-life care experience for third-year medical students at Yale University School of Medicine, which began on a pilot basis in 2005. The primary objectives of the program, which still continues, are to improve students' comfort and skills in communicating with and assessing patients facing the end of life and to reflect on their experiences. Students interview a hospitalized patient, family, and caregivers; assess specified end-of-life domains and management plans; reflect on the experience; and then prepare a report for presentation at a case conference facilitated by dedicated multidisciplinary faculty. Many students interview patients while rotating on psychiatry consults, and the case conference occurs during the psychiatry clerkship. A total of 45 students in the pilot year (2005), 76 students in the following year, and 48 thus far in the current year have completed the program. An assessment of the personal impact of the exercise on the students who completed the program in 2005 and 2006 revealed six themes, including students' recognition of the complexity of patients' reactions to dying, students' appreciation of the value of the clinicians' presence, and students' personal reflections. This experience suggests that a hands-on end-of-life exercise is feasible and will be well received in the acute inpatient setting. Key features for success include separate, dedicated faculty for the case conference (which is integrated into a single clerkship), emphasis on student self-reflection, and a requirement that the written component become part of the student's portfolio.

New Organ Allocation System for Combined Liver-Kidney Transplants and the Availability of Kidneys for Transplant to Patients with Stage 4-5 CKD.

A new proposal has been created for establishing medical criteria for organ allocation in recipients receiving simultaneous liver-kidney transplants. In this article, we describe the new policy, elaborate on the points of greatest controversy, and offer a perspective on the policy going forward. Although we applaud the fact that simultaneous liver-kidney transplant activity will now be monitored and appreciate the creation of medical criteria for allocation in simultaneous liver-kidney transplants, we argue that some of the criteria proposed, especially those for allocating a kidney to a liver recipient with AKI, are too liberal. We call on the nephrology community to follow the consequences of this new policy and push for a re-examination of the longstanding policy of allocating kidneys to multiorgan transplant recipients before all other candidates. The charge to protect our system of equitable organ allocation is very challenging, but it is a challenge that we must embrace.

Demonstrating Medical Student Competency in Palliative Care: Development and Evaluation of a New Objective Structured Clinical Examination Station.

BACKGROUND: The observed structured clinical examination (OSCE) is an important tool to assess clinical competencies; however, there are no reported palliative care OSCEs for medical student assessment. OBJECTIVE: We aimed to develop, implement, and evaluate the characteristics of a palliative care OSCE for fourth-year medical students. METHODS: We created a representative case and a checklist of 14 history items from three core palliative care competency domains. Subjects were fourth-year medical students who had completed our school's longitudinal palliative care curriculum. Measurements were students' scores compiled from the standardized patient's (SP) tally of the checklist results. We determined inter-rater reliability between the SP and a remote observer. Measurements included the difficulty and discrimination index, internal consistency reliability, factor analysis, and relationships between palliative care scores and composite seven station OSCE scores. RESULTS: In the implementation year, 95 students scored an average of 74% (standard deviation [SD] = 13%) on the 14 history items. There was 95% agreement in ratings on items between the SP and the remote observer. The Cronbach's alpha was 0.53, demonstrating moderate internal consistency. The palliative care scores correlated with overall OSCE communication scores (R = 0.29, p = 0.01) and history scores (R = 0.61, p = 0.01). CONCLUSIONS: A new OSCE to assess palliative care competencies was feasible to implement with high inter-rater reliability, evidence supporting validity, and moderate internal consistency. We believe this OSCE would prove useful to assess students' primary palliative care competency and to evaluate curricula in palliative care.

Renal transplant recipients over aged 60 have diminished immune activity and a low risk of rejection.

Strict consideration of the renal transplant candidate's chronologic age is generally supplanted by more subjective reflection on his (her) physiologic state. In the US, patients over 64 years old represented 9.0% of renal transplant recipients in the year 2000, yet little prior experience is available with which to guide the management of geriatric patients. Two hundred and forty six consecutive recipients of primary kidney transplants at the Yale-New Haven Organ Transplant Center between 1990 and 1995 were included in an outcome analysis. Age at transplantation ranged from 2 to 68 years; the study group consisted of the 16 (6.5%) over age 60. The immunosuppressive protocol was uniform for all patients. There was a disproportionately high use of cadaveric organs by older patients; only 1/16 (6.3%) received a living donor kidney. The overall rate of rejection within the first 90 days was 6.7% of cadaveric recipients over 60 versus 37.6% of younger recipients, P=0.001. Actual patient survival rates at 6 years were 100% of patients younger than 11 years versus 69% (11/16) of those older than 60 years. Death censored 5 year graft survival was 100% in older patients versus 85% among the younger patients. The older and younger patients received quantitatively equivalent immunosuppression, but acute rejection was uncommon in the former (6%) versus the younger cohort (34%). It seems logical to consider whether older renal transplant recipients may benefit from a less aggressive immunosuppression strategy.

Oncologic issues and kidney transplantation: a review of frequency, mortality, and screening.

Kidney transplant recipients are at increased risk for development of malignancy compared with the general population, and malignancies occur at an earlier age. This increased risk, as expressed by the standard incidence ratio (SIR), varies widely, but it is highest in malignancies triggered by oncogenic viruses. For other cancers, this increased risk is the direct consequence of immunosuppressants promoting tumor growth and lowering immune system tumor surveillance. In this review, we briefly discuss the common malignancies with increased risk after kidney transplantation, explore the pros and cons associated with screening, and summarize current prevention and treatment recommendations.

Using online learning and interactive simulation to teach spiritual and cultural aspects of palliative care to interprofessional students.

BACKGROUND: To meet the complex needs of patients with serious illness, health professional students require education in basics aspects of palliative care, including how to work collaboratively on an interprofessional team. OBJECTIVES: An educational program was created, implemented, and evaluated with students in medicine, nursing, chaplaincy, and social work. Five learning objectives emphasized spiritual, cultural, and interprofessional aspects of palliative care. DESIGN: The program blended two sequential components: an online interactive, case-based learning module, and a live, dynamic simulation workshop. MEASUREMENTS: Content analysis was used to analyze students' free-text responses to four reflections in the online case, as well as open-ended questions on students' postworkshop questionnaires, which were also analyzed quantitatively. RESULTS: Analysis of 217 students' free-text responses indicated that students of all professions recognized important issues beyond their own discipline, the roles of other professionals, and the value of team collaboration. Quantitative analysis of 309 questionnaires indicated that students of all professions perceived that the program met its five learning objectives (mean response values>4 on a 5-point Likert scale), and highly rated the program and its two components for both educational quality and usefulness for future professional work (mean response values approximately>4). CONCLUSIONS: This innovative interprofessional educational program combines online learning with live interactive simulation to teach professionally diverse students spiritual, cultural, and interprofessional aspects of palliative care. Despite the challenge of balanced professional representation, this innovative interprofessional educational program met its learning objectives, and may be transferable for use in other educational settings.

Should living kidney donor candidates with impaired fasting glucose donate?

As the kidney transplant waiting list grows, the willingness of transplant centers to accept complex donors increases. Guidelines for the evaluation of living kidney donors exist but do not provide clear guidance when evaluating the complex donor. Although few transplant centers will approve donor candidates with impaired glucose tolerance and most, if not all, will deny candidates with diabetes, many will approve candidates with impaired fasting glucose (IFG). Furthermore, the demographic of living donors has changed in the past 10 years to increasingly include more nonwhite and Hispanic individuals who are at greater risk for future diabetes and hypertension. IFG may be more of a concern in potential donors whose nonwhite and Hispanic ethnicity already places them at greater risk. We review the definition of diabetes, diabetes prediction tools, and transplant guidelines for donor screening and exclusion as it pertains to impaired glucose metabolism, and additional ethnic and nonethnic factors to consider. We offer an algorithm to aid in evaluation of potential living donors with IFG in which ethnicity, age, and features of the metabolic syndrome play a role in the decision making.

Effectiveness of an integrated ward-based program in preparing medical students to care for patients at the end of life.

Integrating end-of-life care training into the clinical years of medical school has been promoted to enhance education in this area. To assess the effectiveness of an end-of-life care exercise integrated into clinical clerkships, we compared the level of preparedness in end-of-life care reported by students who did or did not complete the exercise. A greater proportion of students who completed the exercise compared with those who did not felt prepared in end-of-life care [50.7% (39/77) vs 35.6% (64/180); P = .02]. Among 5 domains of skills examined, significant differences were seen in interviewing/communicating (3.7 vs 3.5; P = .05) and management of common symptoms (3.3 vs 3.0; P < .01). We conclude that a ward-based integrated end-of-life care exercise may improve graduating students' self-reported preparedness to care for patients at the end of life.

Evaluation and management of bone disease and fractures post transplant.

Bone disease is common in recipients of kidney, liver, heart, and lung transplants and results in fractures in 20-40% of patients, a rate much higher than expected for age. Fractures occur because of the presence of bone disease as well as other factors such as neuropathy, poor balance, inactivity, and low body or muscle mass. Major contributors to bone disease include both preexisting bone disease and bone loss post transplant, which is greatest in the first 6-12 months when steroid doses are highest. Bone disease in kidney transplant recipients should be considered different from that which occurs in other solid organ transplant recipients for several reasons including the presence of renal osteodystrophy, which contributes to low bone mineral density in these patients; the location of fractures (more common in the legs and feet in these patients than in spine and hips as in other solid organ recipients); and the potential danger in using bisphosphonate therapy, which may cause more harm than good in kidney transplant recipients with low bone turnover. Evaluation in all patients should preferably occur in the pretransplant period or early post transplant and should include assessment of fracture risk as well as metabolic factors that can contribute to bone disease. Bone mineral density measurement is recommended in all patients even if its predictive value for fracture risk in the transplant population is unproven. Management of bone disease should be directed toward decreasing fracture risk as well as improving bone density. Pharmacologic and nonpharmacologic treatment strategies are discussed in this review. Although there have been many studies describing a beneficial effect of bisphosphonates and vitamin D analogues on bone density, none have been powered to detect a decrease in fracture rate.