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People who identify as sexual and/or gender minority individuals face unique and challenging inequities in access to health care. They experience bias, discrimination and underinsurance, which limits their access to high-quality care (including for kidney disease). These inequities must be addressed through the provision of safe and inclusive environments, improved identification of disparities and the creation of a pipeline of equity-focused leaders.

The coronavirus disease 2019 pandemic forced virtual adaptations to social distancing guidelines, including transitions to virtual medical education, conferences, patient care, and even socialization. As the nephrology fellowship recruitment season approached in 2020, training programs across the

Lactate is produced through the metabolism of glucose and subsequently eliminated by both the liver and the kidneys. Lactic acidosis develops when the rate of production of lactate overwhelms the body’s ability to clear it.1 There are 2 main types of L-lactic acidosis: A (ischemic) and B (nonischemic). Etiologies for type B lactic acidosis2 include: liver dysfunction, thiamine deficiency, malignancy, several drug associations, ketoacidosis, and mitochondrial disease (Table 1).3 Table 1 Etiologies of L-lactic acidosis

The use of social media has increased over the last several decades, with ∼72% of the US adult population indicating the use of social networking platforms. Expansion of social media use beyond personal reasons now includes professional uses. This growth is especially true in medicine—and specifically nephrology. An enhanced online presence has the potential to make positive contributions to professional development, education and collaborations, potentially opening doors to academic opportunities. With a growing number of online platforms, resources and conversations, it is natural for one to feel overwhelmed and ultimately avoid social media. We discuss the benefits of social media engagement for nephrologists and provide a practical guide on how they can harness social media professionally and effectively. With an understanding of the basics, existing resources and avoidance of potential pitfalls, physicians can learn to use social media and join the global nephrology community.

Background Digital innovations have the potential to enhance current graduate medical education strategies. Objective We assessed the scope, reach, and effectiveness of Nephrology Simulator (NephSIM), a free, mobile-optimized, nephrology educational tool designed to teach pathophysiology with a diagnostic approach using interactive cases. Methods NephSIM, launched in June 2018, was designed as a mobile-optimized website with peer-reviewed content in WordPress. Content, including interactive cases with iterative feedback, infographics, and tutorials, was developed by nephrology fellows and attending nephrologists. The teaching tool was shared via an e-mail subscriber list and Twitter. Website usage data and Twitter analytics were reviewed. Case content was categorized, and the case completion rate was calculated. A self-report survey was sent to subscribers to assess their demographics and experience. Results Thirty-four cases have been published to date and represent a variety of nephrology topics. There have been 100 745 page views between June 2018 and June 2019, representing 17 922 unique visitors from more than 100 countries. There are 1929 accounts that follow NephSIM on Twitter. Tweets received 124 200 impressions and a 3% engagement rate. Median case completion rate was 69% (interquartile range 64%–78%). Our survey response rate was 17% (76 of 445). Nearly all NephSIM users rated the platform highly in terms of satisfaction and usability, and planned to continue using in the future. Conclusions The development of a mobile-optimized, case-based teaching approach by nephrology fellows and faculty is feasible and has demonstrated global participation and high levels of learner satisfaction.

Understanding and interpretation of acid-base disorders is an important clinical skill that is applicable to the majority of physicians. Although this topic is taught early in medical school, acid-base disturbances have been described as challenging by postgraduate trainees. We describe the use of Twitter, an online microblogging platform, to augment education in acid-base disturbances by using polls in which the user is shown laboratory values and then asked to select the most likely etiology of the disorder. The answer and a brief explanation are then shared in a subsequent tweet. Both polling questions and answers are shared from the account for the online, mobile-optimized, nephrology teaching tool NephSIM ( https://www.nephsim.com/ ). An anonymous survey was administered to assess attitudes toward these polls. Using Twitter as an approach to enhance teaching of acid-base disturbances was both feasible and an engaging way to teach a challenging topic for trainees and physicians. Moreover, the coronavirus disease 2019 (COVID-19) pandemic has demonstrated the importance of incorporating virtual learning opportunities in all levels of medical education.

Background: Sixty percent of U.S. internal medicine (IM) residency directors report their program includes a curriculum focused on the needs of patients with limited English proficiency (LEP). Objective: This quality improvement project sought to improve knowledge of best practices for caring for LEP patients by IM residents by implementing an educational curriculum. Methods: Residents from three IM residency programs in a large academic health system were surveyed on their perceived LEP education and barriers at the beginning of the 2018–2019 academic year. A LEP curriculum was developed and delivered to interns of one of the programs. These residents were re-surveyed early in the following academic year. Results: 118/392 (30%) residents completed the pre-curriculum survey. 35% of respondents reported frustration or stress while caring for LEP patients. 59% of residents reported deferring an interpreter for LEP patients less than half of the time. After implementation of the curriculum, a significantly higher percentage of residents responded they informed patients of LEP services at the beginning of the patient encounter (42% vs. 58%, p = 0.03), used “teach-back” (38% vs. 63%, p = 0.002), and felt confident in their ability to know if the patient understood the interpreter (25% vs. 42%, p = 0.01). There were no significant changes after implementation of the curriculum on the effect of time pressures, deferring of formal interpretation, and use of ad-hoc interpreters. Conclusions: A LEP curriculum delivered as a brief workshop for IM residents increased perceived education in caring for LEP patients and heightened awareness of LEP patient rights to formal interpretation.

BackgroundInterstitial fibrosis, tubular atrophy, and inflammation are major contributors to renal allograft failure. Here we seek an objective, quantitative pathological assessment of these lesions to improve predictive utility.MethodsWe constructed a deep-learning-based pipeline recognizing normal vs. abnormal kidney tissue compartments and mononuclear leukocyte (MNL) infiltrates from Periodic acid-Schiff (PAS) stained slides of transplant biopsies (training: n=60, testing: n=33) that quantified pathological lesions specific for interstitium, tubules and MNL infiltration. The pipeline was applied to 789 whole slide images (WSI) from baseline (n=478, pre-implantation) and 12-month post-transplant (n=311) protocol biopsies in two independent cohorts (GoCAR: 404 patients, AUSCAD: 212 patients) of transplant recipients to correlate composite lesion features with graft loss.ResultsOur model accurately recognized kidney tissue compartments and MNLs. The digital features significantly correlated with Banff scores, but were more sensitive to subtle pathological changes below the thresholds in Banff scores. The Interstitial and Tubular Abnormality Score (ITAS) in baseline samples was highly predictive of 1-year graft loss (p=2.8e-05), while a Composite Damage Score (CDS) in 12-month post-transplant protocol biopsies predicted later graft loss (p=7.3e-05). ITAS and CDS outperformed Banff scores or clinical predictors with superior graft loss prediction accuracy. High/intermediate risk groups stratified by ITAS or CDS also demonstrated significantly higher incidence of eGFR decline and subsequent graft damage.ConclusionsThis deep-learning approach accurately detected and quantified pathological lesions from baseline or post-transplant biopsies, and demonstrated superior ability for prediction of posttransplant graft loss with potential application as a prevention, risk stratification or monitoring tool.

In recent robust randomized control trials (RCTs), sodium-glucose cotransporter 2 (SGLT2) inhibitors (empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin) have been shown to dramatically decrease both kidney and cardiovascular (CV) adverse outcomes in patients with diabetic kidney disease, nondiabetic proteinuric kidney disease, and heart failure with reduced ejection fraction—with and without the presence of diabetes (1–6). For decades, both the nephrologist’s and transplant nephrologist’s arsenal for the management of proteinuric kidney disease has been limited to renin-angiotensin-aldosterone system blockade (7). Although SGLT2 inhibitors have taken the nephrology community by storm, patients with kidney transplants (KTs) have been notably excluded from large RCTs (8–10). Pathophysiologically, it seems likely they would also benefit from these apparent wonder drugs, particularly as many patients with KT have proteinuric kidney disease or heart failure. Similar to patients with native kidney disease, CV mortality is the leading cause of death in the KT population (11). Is it time to allow patients with KT to benefit from proposed SGLT2 inhibitor mechanisms, including tubuloglomerular feedback restoration, decreased inflammation and fibrosis, and alteration in energy metabolism, that all culminate in improved CV and kidney outcomes (12)? Here, we review the available data for SGLT2 inhibitor use in patients with KTs and discuss potential benefits and risk of their use in this population. Since 2015, sequential RCTs have demonstrated efficacy of SGLT2 inhibitors in improving both kidney and CV outcomes. A 2020 meta-analysis included six of these RCTs that studied SGLT2 inhibitor use (empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin) in close to 47,000 patients with diabetes (2). In all of the studies included in the meta-analysis, SGLT2 inhibitor use led to a reduction in heart failure hospitalizations, with empagliflozin being the only drug with significant CV death risk reduction. A reduction in kidney outcomes was seen with all agents …

The shift in learning environments due to the COVID-19 pandemic necessitates a closer look at course design, faculty approaches to teaching, and student interaction, all of which may predict learner achievement and satisfaction. Transitioning to an online environment requires the reinvention, reimagining, and applying of “e-flavors” of general learning theory. With this shift to online learning comes the opportunity for misunderstandings and “myths” to occur, which may stand in the way of faculty embracing online learning and fully realizing its potential. This article seeks to address several myths and misconceptions that have arisen in higher education during the rapid shift to online teaching and learning. While not comprehensive, these myths represent a snapshot of common challenges. These are we can transfer our in-person course design to online; adult learners do not need an empathetic approach; and online teaching and learning is socially isolating. Through an appreciative inquiry framework, we present each myth in the context of relevant literature and invite faculty with varied online teaching experience to share their own case studies that illustrate how they have “busted” these myths with the goal to identify existing examples of locally effective practices for the express purpose of replication that leads to positive change.

The influence of patient characteristics and immunosuppression management on COVID‐19 outcomes in kidney transplant recipients (KTRs) remains uncertain. We performed a single‐center, retrospective review of all adult KTRs admitted to the hospital with confirmed COVID‐19 between 03/15/2020 and 05/15/2020. Patients were followed from the date of admission up to 1 month following hospital discharge or study conclusion (06/15/2020). Baseline characteristics, laboratory parameters, and immunosuppression were compared between survivors and patients who died to identify predictors of mortality. 38 KTRs with a mean baseline eGFR of 52.5 ml/min/1.73 m2 were hospitalized during the review period. Maintenance immunosuppression included tacrolimus (84.2%), mycophenolate (89.5%), and corticosteroids (81.6%) in the majority of patients. Eleven patients (28.9%) died during the hospitalization. Older age (OR = 2.05; 1.04‐4.04), peak D‐dimer (OR = 1.20; 1.04‐1.39), and peak white blood cell count (OR = 1.11; 1.02‐1.21) were all associated with mortality among KTRs hospitalized for COVID‐19. Increased mortality was also observed among KTRs with concomitant HIV infection (87.5% vs. 36.1%; p

Background Although urine microscopy is an important step in the initial evaluation of a patient with kidney disease, internal medicine residents have minimal exposure to this technique during their training. The goal of this study was to understand knowledge of and attitudes toward urine microscopy among internal medicine residents and to implement virtual urine microscopy teaching sessions. Methods A voluntary, anonymous, online survey was sent to all of the categorical internal medicine residents (n=131) training at the Icahn School of Medicine at Mount Sinai (ISMMS). The survey included 13 questions to assess attitudes toward, experience with, and clinical interpretation of urine microscopy specimens. In response to the survey results, we implemented virtual urine microscopy teaching sessions using video conferencing software that incorporated real-time urine sediment analysis with nephrology fellows and attending nephrologists. Results The survey response rate was 45% (59 of 131). Forty-seven percent (28 of 59) of respondents reported performing urine microscopy at least once during their training, and 75% (44 of 59) of respondents did not feel comfortable performing urine microscopy. The majority of residents (92%; 54 of 59) reported they felt urine microscopy was very helpful or somewhat helpful in the evaluation of patients with AKI. Overall, 41% of responses to clinical interpretation questions were considered correct. Following survey completion, virtual urine microscopy sessions were held monthly and well received by the participants. Conclusions Our study found that internal medicine residents perceive urine microscopy as a helpful diagnostic tool, although lack the skills to perform and interpret urine microscopy sediments. Virtual educational sessions using video conferencing software are a technically feasible approach to teaching urine microscopy to internal medicine residents. Future studies include a study of the effect of these sessions on learning of urine microscopy. Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/K360/2021_01_28_KID0006282020.mp3.

Kidney transplant recipients may be at a high risk of developing critical coronavirus disease 2019 (COVID-19) illness due to chronic immunosuppression and comorbidities. We identified hospitalized adult kidney transplant recipients at 12 transplant centers in the United States, Italy, and Spain who tested positive for COVID-19. Clinical presentation, laboratory values, immunosuppression, and treatment strategies were reviewed, and predictors of poor clinical outcomes were determined through multivariable analyses. Among 9845 kidney transplant recipients across centers, 144 were hospitalized due to COVID-19 during the 9-week study period. Of the 144 patients, 66% were male with a mean age of 60 (±12)years, and 40% were Hispanic and 25% were African American. Prevalent comorbidities included hypertension (95%), diabetes (52%), obesity (49%), and heart (28%) and lung (19%) disease. Therapeutic management included antimetabolite withdrawal (68%), calcineurin inhibitor withdrawal (23%), hydroxychloroquine (71%), antibiotics (74%), tocilizumab (13%), and antivirals (14%). During a median follow-up period of 52days (IQR: 16-66days), acute kidney injury occurred in 52% cases, with respiratory failure requiring intubation in 29%, and the mortality rate was 32%. The 46 patients who died were older, had lower lymphocyte counts and estimated glomerular filtration rate levels, and had higher serum lactate dehydrogenase, procalcitonin, and interleukin-6 levels. In sum, hospitalized kidney transplant recipients with COVID-19 have higher rates of acute kidney injury and mortality.

The novel coronavirus disease infection (COVID-19) outbreak that was declared a global pandemic in March 2020 had led to an internationally variable but concerning incidence of COVID-associated acute kidney injury (AKI), with prevalence reported as high as 46% in large cohorts of hospitalized patients. Variability in AKI may be explained by differences in traditional risk factors for AKI, heterogeneity among patient cohorts, and differences in racial and ethnic groups. Further, AKI requiring kidney replacement therapies (KRT) has been associated with increased mortality. Proposed mechanisms of kidney injury include direct viral-induced tubular or glomerular injury, sepsis-associated AKI, and thrombotic disease. Kidney pathology include acute tubular injury, glomerular fibrin thrombi, pigmented tubular casts, and collapsing focal segmental glomerulosclerosis. "Viral-like" particles have been observed in renal samples at electron microscopy and viral RNA has been identified in both glomerular and tubular compartments of kidney specimens, but the link between viral presence and injury remain unclear. Though the link between AKI and poor outcomes is clear, prevalence and outcomes of COVID-19 in patients with chronic kidney disease and end stage kidney disease has not yet been reported. In patients on immunosuppression like those with kidney transplants or glomerular disease, COVID-19 has presented a management dilemma. Herein, we review the existing literature on kidney disease in COVID-19 and discuss what remains to be learned.

As paradigms of clinical care delivery have been significantly impacted by the novel coronavirus disease 2019 (COVID-19) pandemic, so has the structure, delivery, and future of medical education. Both undergraduate and graduate medical education have seen disruptions ranging from fully virtual delivery of educational content and limited clinical care for medical students to increased clinical demands with redeployment for residents and fellows. Adherence to social distancing has led to the adoption and implementation of already available technologies in medical education, including video conferencing softwares and social media platforms. Efficient and effective use of these technologies requires an understanding not only of these platforms and their features, but also of their inherent limitations. During a time of uncertainty and increased clinical demands, the approach to medical education must be thoughtful with attention to wellness of both the educator and learner. In this review, we discuss the influence of the pandemic on the existing medical education landscape, outline existing and proposed adaptations to social distancing, and describe challenges that lie ahead.

Background Kidney transplantation remains the optimal therapy for patients with end stage kidney disease (ESKD), though a small fraction of patients on dialysis are on organ waitlists. An important barrier to both preemptive kidney transplantation and successful waitlisting is timely referral to a kidney transplant center. We implemented a quality improvement strategy to improve outpatient kidney transplant referrals in a single center academic outpatient nephrology clinic. Methods Over a 3 month period (July 1–September 30, 2016), we assessed the baseline kidney transplantation referral rate at our outpatient nephrology clinic for patients 18–75 years old with an estimated glomerular filtration rate (eGFR) of less than 20 mL/min/1.73m2 (2 values over 90 days apart). Charts were manually reviewed by two reviewers to look for kidney transplant referrals and documentation of discussions about kidney transplantation. We then performed a root cause analysis to explore potential barriers to kidney transplantation. Our intervention began on July 1, 2017 and included the implementation of a column in the electronic medical record (EMR) which displayed the patient’s last eGFR as part of the clinic schedule. In addition, physicians were given a document listing their patients to be seen that day with an eGFR of 2. Annual education sessions were also held to discuss the importance of timely kidney transplant referral. Results At baseline, 54 unique patients with eGFR ≤20 ml/min/1.73 m2 were identified who were seen in the Clinic between July 1, 2016 and September 30, 2016. 29.6% (16) eligible patients were referred for kidney transplantation evaluation. 69.5% (37) of these patients were not referred for kidney transplant evaluation. 46.3% (25) did not have documentation regarding kidney transplant in the EMR. nephrologist’s most recent note. Following the intervention, 66 unique patients met criteria for eligibility for kidney transplant evaluation. Kidney transplant referrals increased to 60.6% (p Conclusions Our pilot implementation study of a strategy to improve outpatient kidney transplant referrals showed that a free, simple, scalable intervention can significantly improve kidney transplant referrals in the outpatient setting. This intervention targeted the nephrologist’s role in the transplant referral, and facilitated the process of patient recognition and performing the referral itself without significantly interrupting the workflow. Next steps include further investigation to study the impact of early referral to kidney transplant centers on preemptive and living donor kidney transplantation as well as successful waitlisting.

Medication adverse events are common and often preventable. Patients with diminished kidney function are particularly susceptible to adverse events, especially if the medication's primary means of elimination is through the kidneys. Neurotoxicity from baclofen (80% excreted by the kidneys) is increasingly being recognized in patients with diminished kidney function. Chauvin et al. performed a large population-based retrospective cohort study in patients with end-stage kidney disease (ESKD) and showed a high rate of encephalopathy with hospitalizations shortly after baclofen exposure. This commentary discusses the high rate of altered mental status after baclofen exposure in patients with ESKD, potential reasons for the continued reports of this adverse event, and strategies to educate the health care community.

ImportancePreliminary 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.ObjectiveTo provide information about frequency, outcomes and recovery associated with AKI and dialysis in hospitalized COVID-19 patients.DesignObservational, retrospective study.SettingAdmitted to hospital between February 27 and April 15, 2020.ParticipantsPatients aged ≥18 years with laboratory confirmed COVID-19ExposuresAKI (peak serum creatinine increase of 0.3 mg/dL or 50% above baseline).Main Outcomes and MeasuresFrequency 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.ResultsA 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 RelevanceAKI 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.Key PointsQuestionWhat is incidence and outcomes of acute kidney injury (AKI) in patients hospitalized with COVID-19?FindingsIn this observational study of 3,235 hospitalized patients with COVID-19 in New York City, AKI occurred in 46% of patients and 20% of those patients required dialysis. AKI was associated with increased mortality. 44% of patients discharged alive had residual acute kidney disease. A machine learned predictive model using baseline features for dialysis requirement had an AUC Of 0.79.MeaningAKI was common in patients with COVID-19, associated with increased mortality, and nearly half of patients had acute kidney disease on discharge.

Background and objectives FSGS recurrence after kidney transplantation is a major risk factor for graft loss. However, the natural history, clinical predictors, and response to treatment remain unclear because of small sample sizes and poor generalizability of single-center studies, and disease misclassification in registry-based studies. We therefore aimed to determine the incidence, predictors, and treatment response of recurrent FSGS in a large cohort of kidney transplant recipients. Design, setting, participants, & measurements The Post-Transplant Glomerular Disease (TANGO) project is an observational, multicenter, international cohort study that aims to investigate glomerular disease recurrence post-transplantation. Transplant recipients were screened for the diagnosis of idiopathic FSGS between 2005 and 2015 and details were recorded about the transplant, clinical outcomes, treatments, and other risk factors. Results Among 11,742 kidney transplant recipients screened for FSGS, 176 had a diagnosis of idiopathic FSGS and were included. FSGS recurred in 57 patients (32%; 95% confidence interval [95% CI], 25% to 39%) and 39% of them lost their graft over a median of 5 (interquartile range, 3.0–8.1) years. Multivariable Cox regression revealed a higher risk for recurrence with older age at native kidney disease onset (hazard ratio [HR], 1.37 per decade; 95% CI, 1.09 to 1.56). Other predictors were white race (HR, 2.14; 95% CI, 1.08 to 4.22), body mass index at transplant (HR, 0.89 per kg/m2; 95% CI, 0.83 to 0.95), and native kidney nephrectomies (HR, 2.76; 95% CI, 1.16 to 6.57). Plasmapheresis and rituximab were the most frequent treatments (81%). Partial or complete remission occurred in 57% of patients and was associated with better graft survival. Conclusions Idiopathic FSGS recurs post-transplant in one third of cases and is associated with a five-fold higher risk of graft loss. Response to treatment is associated with significantly better outcomes but is achieved in only half of the cases.

In kidney transplantation, short-term allograft survival has improved due to improvements in acute rejection episodes without corresponding improvements in long-term survival. Although current organ allocation algorithms take into account human leukocyte antigen (HLA) matching to reduce antidonor alloimmune responses, it is likely that genomic variation at non-HLA loci (ie, non-HLA donor-recipient [D-R] pair mismatches) play a role in the "non-self" responses and ultimately affect long-term allograft survival. Existing data from both animal models and human studies suggest an association between non-HLA D-R mismatches and kidney allograft outcomes. In this minireview, we examine existing and emerging data and discuss putative mechanisms on the role of non-HLA D-R mismatches on long-term allograft outcomes in kidney transplantation.

Background Incidence of the opportunistic infection Pneumocystis jirovecii pneumonia (PJP) in solid organ transplant patients ranges from 5 to 15% with a mortality of up to 38%. Case presentation We present a liver transplant recipient who developed hypoxemic respiratory failure related to PJP soon after treatment for allograft rejection. His presentation was preceded by severe hypercalcemia of 14.6 mg/dL and an ionized calcium of 1.7 mmol/L which remained elevated despite usual medical management and eventually required renal replacement therapy. As approximately 5% of PJP cases have granulomas, here we review the role of pulmonary macrophages and inflammatory cytokines in the pathophysiology of granuloma-mediated hypercalcemia. We also discuss the interpretation of our patient’s laboratory studies, response to medical therapy, and clinical risk factors which predisposed him to PJP. Conclusions It is important for clinicians to consider PJP as an etiology of granulomatous pneumonia and non-parathyroid hormone mediated hypercalcemia in chronically immunosuppressed organ transplant recipients for timely diagnosis and management.

Calcineurin inhibitors (CNIs) are both the savior and Achilles' heel of kidney transplantation. Although CNIs have significantly reduced rates of acute rejection, their numerous toxicities can plague kidney transplant recipients. By 10 years, virtually all allografts will have evidence of CNI nephrotoxicity. CNIs have been strongly associated with hypertension, dyslipidemia, and new onset of diabetes after transplantation—significantly contributing to cardiovascular risk in the kidney transplant recipient. Multiple electrolyte derangements including hyperkalemia, hypomagnesemia, hypercalciuria, metabolic acidosis, and hyperuricemia may be challenging to manage for the clinician. Finally, CNI-associated tremor, gingival hyperplasia, and defects in hair growth can have a significant impact on the transplant recipient’s quality of life. In this review, the authors briefly discuss the pharmacokinetics of CNI and discuss the numerous clinically relevant toxicities of commonly used CNIs, cyclosporine and tacrolimus.

Commonly available clinical parameters fail to predict early acute cellular rejection (EAR, occurring within 6 months after transplant), a major risk factor for graft loss after kidney transplantation. We performed whole-blood RNA sequencing at the time of transplant in 235 kidney transplant recipients enrolled in a prospective cohort study (Genomics of Chronic Allograft Rejection [GoCAR]) and evaluated the relationship of pretransplant transcriptomic profiles with EAR. EAR was associated with downregulation of NK and CD8(+) T cell gene signatures in pretransplant blood. We identified a 23-gene set that predicted EAR in the discovery (n = 81, and AUC = 0.80) and validation (n = 74, and AUC = 0.74) sets. Exclusion of recipients with 5 or 6 HLA donor mismatches increased the AUC to 0.89. The risk score derived from the gene set was also significantly associated with acute cellular rejection after 6 months, antibody-mediated rejection and/or de novo donor-specific antibodies, and graft loss in a cohort of 154 patients, combining the validation set and additional GoCAR patients with surveillance biopsies between 6 and 24 months (n = 80) posttransplant. This 23-gene set is a potentially important new tool for determination of the recipient’s immunological risk before kidney transplantation, and facilitation of an individualized approach to immunosuppressive therapy.

Supplemental Digital Content is available in the text., Background. Pretransplant interferon-γ enzyme-linked immunospot (IFN-γ ELISPOT) has been proposed as a tool to quantify alloreactive memory T cells and estimate the risk of acute rejection (AR) after kidney transplantation, but studies have been inconclusive so far. We performed a meta-analysis to evaluate the association between pretransplant IFN-γ ELISPOT and AR and assess its predictive accuracy at the individual level. Methods. We estimated the pooled summary of odds ratio for AR and the joined sensitivity and specificity for predicting AR using random-effects and hierarchical summary receiver-operating characteristic models. We used meta-regression models with the Monte Carlo permutation method to adjust for multiple tests to explain sensitivity and specificity heterogeneity across studies. The meta-analytic estimates of sensitivity and specificity were used to calculate positive and negative predictive values across studies. Results. The analysis included 12 studies and 1181 patients. IFN-γ ELISPOT was significantly associated with increased AR risk (odds ratio: 3.29; 95% confidence interval (CI), 2.34-4.60); hierarchical summary receiver operating characteristic jointly estimated sensitivity and specificity values were 64.9% (95% CI, 53.7%-74.6%) and 65.8% (95% CI, 57.4%-73.5%), respectively, with moderate heterogeneity across studies. After adjusting for multiple testing, meta-regression models showed that thymoglobulin induction, recipient black ethnicity, living versus deceased donors, and geographical location did not affect sensitivity or specificity. Because of the varying AR incidence of the studies, positive and negative predictive values ranged between 16%–60% and 70%–95%, respectively. Conclusions. Pretransplant IFN-γ ELISPOT is significantly associated with increased risk of AR but provides suboptimal predictive ability at an individual level. Prospective randomized clinical trials are warranted.

Background In kidney transplant recipients, surveillance biopsies can reveal, despite stable graft function, histologic features of acute rejection and borderline changes that are associated with undesirable graft outcomes. Noninvasive biomarkers of subclinical acute rejection are needed to avoid the risks and costs associated with repeated biopsies. Methods We examined subclinical histologic and functional changes in kidney transplant recipients from the prospective Genomics of Chronic Allograft Rejection (GoCAR) study who underwent surveillance biopsies over 2 years, identifying those with subclinical or borderline acute cellular rejection (ACR) at 3 months (ACR-3) post-transplant. We performed RNA sequencing on whole blood collected from 88 individuals at the time of 3-month surveillance biopsy to identify transcripts associated with ACR-3, developed a novel sequencing-based targeted expression assay, and validated this gene signature in an independent cohort. Results Study participants with ACR-3 had significantly higher risk than those without ACR-3 of subsequent clinical acute rejection at 12 and 24 months, faster decline in graft function, and decreased graft survival in adjusted Cox analysis. We identified a 17-gene signature in peripheral blood that accurately diagnosed ACR-3, and validated it using microarray expression profiles of blood samples from 65 transplant recipients in the GoCAR cohort and three public microarray datasets. In an independent cohort of 110 transplant recipients, tests of the targeted expression assay on the basis of the 17-gene set showed that it identified individuals at higher risk of ongoing acute rejection and future graft loss. Conclusions Our targeted expression assay enabled noninvasive diagnosis of subclinical acute rejection and inflammation in the graft and may represent a useful tool to risk-stratify kidney transplant recipients.

Medical education has changed substantially over the last decade. Traditional modes of acquiring medical information, including textbooks and journal articles, have evolved into a more inclusive learning experience. Social media, such as blogs, Twitter, and user-produced videos, created by anyone

Background Long-term outcomes in kidney transplantation (KT) have not significantly improved during the past twenty years. Despite being a leading cause of graft failure, glomerular disease (GD) recurrence remains poorly understood, due to heterogeneity in disease pathogenesis and clinical presentation, reliance on histopathology to confirm disease recurrence, and the low incidence of individual GD subtypes. Large, international cohorts of patients with GD are urgently needed to better understand the disease pathophysiology, predictors of recurrence, and response to therapy. Methods The Post-TrANsplant GlOmerular Disease (TANGO) study is an observational, multicenter cohort study initiated in January 2017 that aims to: 1) characterize the natural history of GD after KT, 2) create a biorepository of saliva, blood, urine, stools and kidney tissue samples, and 3) establish a network of patients and centers to support novel therapeutic trials. The study includes 15 centers in America and Europe. Enrollment is open to patients with biopsy-proven GD prior to transplantation, including IgA nephropathy, membranous nephropathy, focal and segmental glomerulosclerosis, atypical hemolytic uremic syndrome, dense-deposit disease, C3 glomerulopathy, complement- and IgG-positive membranoproliferative glomerulonephritis or membranoproliferative glomerulonephritis type I-III (old classification). During phase 1, patient data will be collected in an online database. The biorepository (phase 2) will involve collection of samples from patients for identification of predictors of recurrence, biomarkers of disease activity or response to therapy, and novel pathogenic mechanisms. Finally, through phase 3, we will use our multicenter network of patients and centers to launch interventional studies. Discussion Most prior studies of post-transplant GD recurrence are single-center and retrospective, or rely upon registry data that frequently misclassify the cause of kidney disease. Systematically determining GD recurrence rates and predictors of clinical outcomes is essential to improving post-transplant outcomes. Furthermore, accurate molecular phenotyping and biomarker development will allow better understanding of individual GD pathogenesis, and potentially identify novel drug targets for GD in both native and transplanted kidneys. The TANGO study has the potential to tackle GD recurrence through a multicenter design and a comprehensive biorepository.

Regenerative medicine promises to meet two of the most urgent needs of modern organ transplantation, namely immunosuppression-free transplantation and an inexhaustible source of organs. Ideally, bioengineered organs would be manufactured from a patient's own biomaterials-both cells and the supporting scaffolding materials in which cells would be embedded and allowed to mature to eventually regenerate the organ in question. While some groups are focusing on the feasibility of this approach, few are focusing on the immunogenicity of the scaffolds that are being developed for organ bioengineering purposes. This review will succinctly discuss progress in the understanding of immunological characteristics and behavior of different scaffolds currently under development, with emphasis on the extracellular matrix scaffolds obtained decellularized animal or human organs which seem to provide the ideal template for bioengineering purposes.

Summary Objectives Plasma C-reactive protein (CRP) is associated with cardiovascular disease (CVD), but effects may vary by gender and degree of CVD risk. Whether CRP has value as a CVD risk marker in type-2 diabetes (T2DM) is unclear. We examined whether CRP has gender differences in association with coronary artery calcium (CAC) in diabetic and nondiabetic samples without clinical CVD. Methods We performed cross-sectional analyses of gender influence on CRP association with CAC in the Penn Diabetes Heart Study (N = 1299 with T2DM), the Study of Inherited Risk of Coronary Atherosclerosis (N = 860 nondiabetic subjects) and a combined sample. Results Female gender was associated with higher plasma CRP in diabetic and nondiabetic samples after adjustment for covariates. There was a strong interaction by gender in the association of CRP with CAC (interaction P