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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants are expected to be resistant to Bebtelovimab (BEB) monoclonal antibody (MAb) and the real-world experience regarding its effectiveness is scarce. This retrospective cohort study reports a data analysis in Banner Healthcare System (a large not-for-profit organization) between 4/5/2022 and 8/1/2022 and included 19,778 Coronavirus disease-19 (COVID-19) positive (by PCR or direct antigen testing) patients who were selected from Cerner-Electronic Health Record after the exclusions criteria were met. The study index date for cohort was determined as the date of BEB MAb administration or the date of the first positive COVID-19 testing. The cohort consist of COVID-19 infected patients who received BEB MAb (N=1,091) compared to propensity score (PS) matched control (N=1,091). The primary outcome was the incidence of 30-day all-cause hospitalization and/or mortality. All statistical analyses were conducted on the paired (matched) dataset. For the primary outcome, the event counts and percentages were reported. Ninety-five percent Clopper-Pearson confidence intervals for percentages were computed. The study cohorts were 1:1 propensity matched without replacement across 26 covariates using an optimal matching algorithm that minimizes the sum of absolute pairwise distance across the matched sample after fitting and using logistic regression as the distance function. The pairs were matched exactly on patient vaccination status, BMI group, age group and diabetes status. Compared to the PS matched control group (2.6%; 95% confidence interval [CI]: 1.7%, 3.7%), BEB MAb use (2.2%; 95% CI: 1.4%, 3.3%) did not significantly reduce the incidence of the primary outcome (p=0.67). In the subgroup analysis, we observed similar no-difference trends regarding the primary outcomes for the propensity rematched BEB MAb treated and untreated groups, stratified by patient vaccination status, age (

Reduction of immunosuppression (IS) upon detection of Polyomavirus (BK) viremia is widely used to prevent BK virus nephropathy. This retrospective case-control study assesses the frequency of de novo donor-specific antibodies (dnDSA) in renal transplant recipients with IS modulation due to BK viremia and the associated risk of antibody mediated rejection.Our cohort included recipients of kidney transplantation between 2007 and 2017 with clinical, HLA antibody, and biopsy data. BK positivity was defined as viremia10 000 c/ml or biopsy proven BK nephropathy. A total of 190 BK cases matched our inclusion criteria, each case was matched with two controls based on gender, donor type, and transplant within 1 year (N = 396).Despite lower number of HLA antigen mismatches (mean = 3.5 vs. 4.4, p.001), dnDSA rates were higher in BK cases than in control group (22.1% vs. 13.9%, p = .02), with the majority detected following IS reduction for BK infection, and arising earlier posttransplant compared with no BK infection (294d vs. 434d, p.001). Antibody mediated rejection rates were similar between cases and controls (8.9% and 8.3%, respectively), but rejection was more likely to occur earlier posttransplant in the BK cases (354d vs. 602d, p = .03).Our data suggest a link between IS reduction and the generation of dnDSA and/or rejection, supporting close monitoring for DSA in patients with reduced IS due to BK infection given their increased risk to develop dnDSA.

IntroductionWhile living donor (LD) kidney transplantation is the optimal treatment for patients with kidney failure, LDs assume a higher risk of future kidney failure themselves. LDs of African ancestry have an even greater risk of kidney failure post-donation than White LDs. Because evidence suggests that Apolipoprotein L1 (APOL1) risk variants contribute to this greater risk, transplant nephrologists are increasingly usingAPOL1genetic testing to evaluate LD candidates of African ancestry. However, nephrologists do not consistently perform genetic counselling with LD candidates aboutAPOL1due to a lack of knowledge and skill in counselling. Without proper counselling,APOL1testing will magnify LD candidates’ decisional conflict about donating, jeopardising their informed consent. Given cultural concerns about genetic testing among people of African ancestry, protecting LD candidates’ safety is essential to improve informed decisions about donating. Clinical ‘chatbots’, mobile apps that provide genetic information to patients, can improve informed treatment decisions. No chatbot onAPOL1is available and no nephrologist training programmes are available to provide culturally competent counselling to LDs aboutAPOL1. Given the shortage of genetic counsellors, increasing nephrologists’ genetic literacy is critical to integrating genetic testing into practice.Methods and analysisUsing a non-randomised, pre–post trial design in two transplant centres (Chicago, IL, and Washington, DC), we will evaluate the effectiveness of culturally competentAPOL1testing, chatbot and counselling on LD candidates’ decisional conflict about donating, preparedness for decision-making, willingness to donate and satisfaction with informed consent and longitudinally evaluate the implementation of this intervention into clinical practice using theReach,Effectiveness,Adoption,Implementation andMaintenance framework.Ethics and disseminationThis study will create a model forAPOL1testing of LDs of African ancestry, which can be implemented nationally via implementation science approaches.APOL1will serve as a model for integrating culturally competent genetic testing into transplant and other practices to improve informed consent. This study involves human participants and was approved by Northwestern University IRB (STU00214038). Participants gave informed consent to participate in the study before taking part.Trial registrationClinicalTrials.gov Identifier:NCT04910867. Registered 8 May 2021,https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000AWZ6&selectaction=Edit&uid=U0001PPF&ts=7&cx=-8jv7m2ClinicalTrials.gov Identifier:NCT04999436. Registered 5 November 2021,https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000AYWW&selectaction=Edit&uid=U0001PPF&ts=11&cx=9tny7v

Kidney transplantation is the preferred treatment for kidney failure; however after transplant, reduced physical function, poor self-perceptions, and unemployment are common concerns that remain. This randomized controlled trial compared the effects of a 12-month exercise rehabilitation program (intervention) to standard care alone (control) in kidney transplant recipients. The exercise intervention consisted of a 2 day/week, 60-minute personalized, one-on-one, resistance-based exercise trainings. Eighty participants completed the study (52 intervention vs. 28 control). For individuals unemployed at baseline, there was a 52.3% increase in employment compared to 13.3 % increase in the control group after 12 months (P =

Background Studies have documented AKI with high-grade proteinuria in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In some patients, biopsies have revealed collapsing glomerulopathy, a distinct form of glomerular injury that has been associated with other viruses, including HIV. Previous patient reports have described patients of African ancestry who developed nephrotic-range proteinuria and AKI early in the course of disease. Methods In this patient series, we identified six patients with coronavirus disease 2019 (COVID-19), AKI, and nephrotic-range proteinuria. COVID-19 was diagnosed by a positive nasopharyngeal swab RT-PCR for SARS-CoV-2 infection. We examined biopsy specimens from one transplanted kidney and five native kidneys. Three of the six patients underwent genetic analysis of APOL1, the gene encoding the APOL1 protein, from DNA extracted from peripheral blood. In addition, we purified genomic DNA from paraffin-embedded tissue and performed APOL1 genotype analysis of one of the native biopsies and the donor kidney graft. Results All six patients were of recent African ancestry. They developed COVID-19-associated AKI with podocytopathy, collapsing glomerulopathy, or both. Patients exhibited generally mild respiratory symptoms, and no patient required ventilator support. Genetic testing performed in three patients confirmed high-risk APOL1 genotypes. One APOL1 high-risk patient developed collapsing glomerulopathy in the engrafted kidney, which was transplanted from a donor who carried a low-risk APOL1 genotype; this contradicts current models of APOL1-mediated kidney injury, and suggests that intrinsic renal expression of APOL1 may not be the driver of nephrotoxicity and specifically, of podocyte injury. Conclusions Glomerular disease presenting as proteinuria with or without AKI is an important presentation of COVID-19 infection and may be associated with a high-risk APOL1 genotype.

In the era of immunotherapy for cancer, solid organ transplant patients who go on to develop metastatic or locally advanced melanoma offer particularly difficult challenges. New approaches are needed for these patients. We present a case of in-transit metastatic melanoma in a renal transplant patient. The patient was initially managed with talimogene laherparepvec (T-VEC) injections alone with continued local progression. Addition of topical imiquimod 5% cream to intralesional T-VEC resulted in a rapid and dramatic response, with complete clearance of the cutaneous in-transit metastases and without any sign of organ rejection. In solid organ transplant patients who lack surgical options and are not eligible for treatment with a BRAF inhibitor, and for whom treatment with checkpoint inhibitors present risk of organ rejection, T-VEC either alone or in combination with topical imiquimod should be considered for patients with locally advanced disease. This combination should be a consideration, with close observation, in patients with a history of organ transplantation and immunosuppression.

Summary Retrospective analysis of the post–propensity score (PS)–matched cohort of 8426 outpatients balanced in clinical and demographic covariates showed that treatment with casirivimab-imdevimab monoclonal antibody was effective against the SARS-CoV-2 Delta variant to reduce hospitalization, mortality, and intensive care unit admission rates within 30 days. Background Real-world data on the effectiveness of neutralizing casirivimab-imdevimab monoclonal antibody (Cas-Imd mAb) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among high-risk patients may inform the response to future SARS-CoV-2 variants. Methods This study covers an observational retrospective data analysis in Banner Health Care System sites, mainly in Arizona. During the study period, the prevalence of SARS-CoV-2 Delta variant was between 95% and 100%. Of 29 635 patients who tested positive for coronavirus disease 2019 (COVID-19) between 1 August 2021 and 30 October 2021, in the Banner Health Care System, the study cohort was split into 4213 adult patients who received Cas-Imd mAb (1200 mg) treatment compared to a PS-matched 4213 untreated patients. The primary outcomes were the incidence of all-cause hospitalization, intensive care unit (ICU) admission, and mortality within 30 days of Cas-Imd mAb administration or Delta variant infection. Results Compared to the PS-matched untreated cohort, the Cas-Imd mAb cohort had significantly lower all-cause hospitalization (4.2% vs 17.6%; difference in percentages, −13.4 [95% confidence interval {CI}, −14.7 to −12.0]; P Conclusions Cas-Imd mAb treatment was associated with a lower hospitalization rate, ICU admission, and mortality within 30 days among patients infected with the SARS-CoV-2 Delta variant.

PURPOSE OF REVIEW: In this paper, we seek to review coronavirus disease 2019 (COVID-19) associated kidney injury with a focus on what is known about pathophysiology. RECENT FINDINGS: Kidney injury is a common complication of SARS-CoV-2 infection and is associated with increased morbidity and mortality. Acute tubular necrosis and glomerular injury are two common findings. Direct viral effect, endothelial dysfunction, and podocyte and tubular epithelial injury have been described. COVID-19-related glomerular injury may also be associated with high-risk APOL1 genotype. SUMMARY: Data on COVID-19 renal involvement have suggested novel mechanisms of kidney injury that need to be further elucidated. More data are needed on renal involvement in milder disease, renal-specific therapeutic interventions, and long-term sequelae.

Background Kidney transplant recipients are a unique cohort in regard to SARS-CoV 2 susceptibility and clinical course, owing to their immunosuppressed state and propensity for kidney injury. The primary purpose of this study is to ascertain if, in kidney transplant recipients, SARS-CoV 2 infection impacts long term renal allograft function. Methods This retrospective, single-center study reviewed 53 kidney transplant recipients with a positive SARS-CoV-2 PCR at NMH from January 1, 2020 to June 30, 2020. Results Change in eGFR from baseline kidney function prior to infection to 90 days after the first positive SARS-CoV 2 test was +1.76%, -17.5% and -23.16% the mild, moderate and severe disease groups respectively. There was a significant decline in kidney function in the moderate and severe disease cohorts as compared to the mild disease cohort, with respective p values of p = 0.0002 and p = 0.021. Relative to the mild disease cohort, the moderate and severe disease cohorts also demonstrated significantly increased risk of developing AKI (66%, 85%), both with p values of P = 0.0001. Conclusions Clinically severe SARS-CoV 2 infection is associated with greater risk of acute kidney injury and greater decline in renal allograft function at 90 days post infection, compared to mild disease.

We report a case of a 50‐year‐old male with a history of HIV and kidney transplant who presented with SARS‐CoV‐2. We also present a review of COVID‐19 cases in kidney transplant recipients.

Homozygosity for apolipoprotein-L1 (APOL1) risk variants has emerged as an important predictor of renal disease in individuals of African descent over the past several years. Additionally, these risk variants may be important predictors of renal allograft failure when present in a living or deceased donor. Currently, there is no universal recommendation for screening of potential donors. We present a case of end-stage renal disease with focal segmental glomerulosclerosis in a living donor 7 years following donor nephrectomy. Genetic assessment revealed homozygosity for the G1 high-risk APOL1 variant.

Calcineurin inhibitors (CNI), the cornerstone of immunosuppression after transplantation are implicated in nephrotoxicity and allograft dysfunction. We hypothesized that combined low doses of CNI and Everolimus (EVR) may result in better graft outcomes and greater tolerogenic milieu. Forty adult renal transplant recipients were prospectively randomized to (steroid free) low dose Tacrolimus (TAC) and EVR or standard dose TAC and Mycophenolate (MMF) after Alemtuzumab induction. Baseline characteristics were statistically similar. EVR levels were maintained at 3-8 ng/ml. TAC levels were 4.5±1.9 and 6.4±1.5 ng/ml in the TAC+EVR and TAC+MMF group respectively. Follow up was 14±4 and 17±5 months respectively and included protocol kidney biopsies at 3 and 12 months post-transplantation. Rejection-rate was lower in the TAC+EVR group. However patient and overall graft survival, eGFR and incidence of adverse events were similar. TAC+EVR induced expansion of CD4+CD25hiFoxp3+ regulatory T cells as early as 3 months and expansion of IFN-γ+CD4+CD25hiFoxp3+ regulatory T cells at 12 months post-transplant. Gene expression profile showed a trend toward decreased inflammation, angiogenesis and connective tissue growth in the TAC+EVR Group. Thus, greater tolerogenic mechanisms were found to be operating in patients with low dose TAC+EVR and this might be responsible for the lower rejection-rate than in patients on standard dose TAC+MMF. However, further studies with longer follow up and evaluating impact on T regulatory cells are warranted.

The modern immunosuppression regimen has greatly improved short-term allograft outcomes but not long-term allograft survival. Complications associated with immunosuppression, specifically nephrotoxicity and infection risk, significantly affect graft and patient survival. Inducing and understanding pathways underlying clinical tolerance after transplantation are, therefore, necessary. We previously showed full donor chimerism and immunosuppression withdrawal in highly mismatched allograft recipients using a bioengineered stem cell product (FCRx). Here, we evaluated the gene expression and microRNA expression profiles in renal biopsy samples from tolerance-induced FCRx recipients, paired donor organs before implant, and subjects under standard immunosuppression (SIS) without rejection and with acute rejection. Unlike allograft samples showing acute rejection, samples from FCRx recipients did not show upregulation of T cell- and B cell-mediated rejection pathways. Gene expression pathways differed slightly between FCRx samples and the paired preimplantation donor organ samples, but most of the functional gene networks overlapped. Notably, compared with SIS samples, FCRx samples showed upregulation of genes involved in pathways, like B cell receptor signaling. Additionally, prediction analysis showed inhibition of proinflammatory regulators and activation of anti-inflammatory pathways in FCRx samples. Furthermore, integrative analyses (microRNA and gene expression profiling from the same biopsy sample) identified the induction of regulators with demonstrated roles in the downregulation of inflammatory pathways and maintenance of tissue homeostasis in tolerance-induced FCRx samples compared with SIS samples. This pilot study highlights the utility of molecular intragraft evaluation of pathways related to FCRx-induced tolerance and the use of integrative analyses for identifying upstream regulators of the affected downstream molecular pathways.

Background— There is controversy about preferred methods to relieve obstruction in hypertrophic cardiomyopathy patients still symptomatic after β-blockade or verapamil. Methods and Results— Of 737 patients prospectively registered at our institution, 299 (41%) required further therapy for obstruction for limiting symptoms, rest gradient 61±45, provoked gradient 115±49 mm Hg, and followed up for 4.8 years. Disopyramide was added in 221 (74%) patients and pharmacological control of symptoms was achieved in 141 (64%) patients. Overall, 138 (46%) patients had surgical relief of obstruction (91% myectomy) and 6 (2%) alcohol septal ablation. At follow-up, resting gradients in the 299 patients had decreased from 61±44 to 10±25 mm Hg ( P P P =0.28). Only 1 patient had sudden death, a low annual rate of 0.06%/y. Kaplan–Meier survival at 10 years in the advanced-care patients did not differ from that expected in a matched cohort of the US population ( P =0.90). Conclusions— Patients with obstruction and symptoms resistant to initial pharmacological therapy with β-blockade or verapamil may realize meaningful symptom relief and low mortality through stepped management, adding disopyramide in appropriately selected patients, and when needed, by surgical myectomy.

Health-related quality of life (HRQOL) provides a measure of patients’ perception of their symptoms, overall health or disability, and treatment. As such, HRQOL is an important patient-centered outcome and transplant-oriented clinical research endpoint. HRQOL alone, or in tandem with other objective clinical outcome measures, is useful in monitoring clinical practice, informing treatment decisions, and guiding the allocation of healthcare resources. It comprises three domains: physical, mental, and psychosocial wellbeing; and can be measured by generalized or targeted instruments depending on the degree of specificity desired by the clinician or researcher. Patients with end stage renal disease requiring dialysis report diminished quality of life compared to the general population, which in turn is associated with an increased risk of hospitalization and death, particularly in those with a high comorbidity burden. Renal transplantation confers a global quality of life benefit. Physical symptoms like pain, poor sleep quality, and fatigue are perceived to be improved after transplantation by renal transplant recipients with a functioning allograft. Depression and anxiety also improve after transplantation as does social participation and integration. However, on average, HRQOL following renal transplant remains lower than in the general population, partly due to transplant related complications like infection and malignancy and the adverse effects of immunosuppression. Other factors that negatively impact HRQOL after transplant include older recipient age, deceased donor transplantation, female gender, lack of social support, and comorbid conditions such as diabetes and depression. Improved HRQOL after kidney transplantation, especially in the physical domain, has been associated with better patient and allograft survival. Hence it is imperative for transplant clinicians to familiarize themselves with the concepts, measurement, and interpretation of HRQOL as they strive to provide comprehensive care to kidney transplant patients.

Kidney transplantation is the treatment of choice for patients with end-stage renal disease, providing a survival and quality of life benefit to the recipient over patients on dialysis. While the survival trend for kidney transplant recipients has steadily improved over the years, the rate of death with a functioning renal allograft remains largely unchanged. Donor and recipient selection impacts both recipient and graft survival and the newly introduced longevity matching-based Kidney Allocation System attempts to capture this association. It is interesting to note that while short-term graft survival has improved significantly over the years, long-term graft survival has not seen an equivalent rise. Various factors including subclinical rejection, immunosuppressive toxicity and chronic allograft dysfunction have been implicated. Protocol renal allograft biopsies serve to provide biological and immunological markers of these factors and biopsy endpoints have been shown to be associated with long-term graft survival. We used laboratory and pathology data after transplant to independently develop a late outcome surrogate score providing a prediction model for graft survival following kidney transplantation. Further effort into developing novel biomarkers and quality predictive models of long-term graft survival is needed.

Background This randomized controlled trial (RCT) will investigate the effects of a personalized exercise rehabilitation regimen on return to work and find work rate, vascular health, functional capacity, quality of life, kidney function, and body composition in kidney transplant (KT) recipients. Methods/design This RCT will recruit 120 men and/or women who have had a KT to participate in a 12 month exercise intervention or control (standard clinical care only) group. The 12 month exercise intervention will consist of one-on-one, progressive exercise rehabilitation sessions twice a week, for 60 min each session. The control group will continue standard clinical care as recommended by their post-transplant medical team without any intervention. The primary outcomes will be assessments of vascular structure and function, walking and strength measures to assess functional capacity, blood markers to assess kidney function, questionnaires to assess quality of life, DXA body scan to assess body composition, and a 1-week free living physical activity assessment. Additionally, employment status will be assessed. These assessments will be performed at baseline, 6 months, and 12 months. Discussion This investigation will increase the understanding of the role exercise rehabilitation has on managing the physiological and psychological health of the individual as well as on the individual's personal economic impact (via employment status). This study design has the potential to assist in constructing an effective exercise rehabilitation program that can be incorporated into part of standard post-transplant care.

The Accreditation Council for Graduate Medical Education (ACGME) introduced new work hour limitations in July 2011.The aim is to assess internal medicine residents' perspectives on the impact of these limitations on their ability to discharge patient care duties.An anonymous survey was administered to 158 medicine residents in an urban university-affiliated internal medicine residency program. Residents' perspectives on various aspects of patient care were recorded on a 5-point Likert-type scale.The response rate was 62%. The majority of residents (80%) agreed that patients had adequate continuity of care. Most residents agreed that they had enough time to follow up on consult notes (64% agreed) and investigations (80% agreed) daily. Most PGY-1 residents (59%) reported having enough time to prepare sign-outs. Most (60%) residents felt that reducing handoffs would improve patient care.Most residents believe that the new work hour limitations would continue to uphold patient safety, but handoffs in care must be restricted.