Preventing Rejection of the Kidney Transplant.

With increasing knowledge of immunologic factors and with the advent of potent immunosuppressive agents, the last several decades have seen significantly improved kidney allograft survival. However, despite overall improved short to medium-term allograft survival, long-term allograft outcomes remain unsatisfactory. A large body of literature implicates acute and chronic rejection as independent risk factors for graft loss. In this article, we review measures taken at various stages in the kidney transplant process to minimize the risk of rejection. In the pre-transplant phase, it is imperative to minimize the risk of sensitization, aim for better HLA matching including eplet matching and use desensitization in carefully selected high-risk patients. The peri-transplant phase involves strategies to minimize cold ischemia times, individualize induction immunosuppression and make all efforts for better HLA matching. In the post-transplant phase, the focus should move towards individualizing maintenance immunosuppression and using innovative strategies to increase compliance. Acute rejection episodes are risk factors for significant graft injury and development of chronic rejection thus one should strive for early detection and aggressive treatment. Monitoring for DSA development, especially in high-risk populations, should be made part of transplant follow-up protocols. A host of new biomarkers are now commercially available, and these should be used for early detection of rejection, immunosuppression modulation, prevention of unnecessary biopsies and monitoring response to rejection treatment. There is a strong push needed for the development of new drugs, especially for the management of chronic or resistant rejections, to prolong graft survival. Prevention of rejection is key for the longevity of kidney allografts. This requires a multipronged approach and significant effort on the part of the recipients and transplant centers.

Ischemic tolerance and cardiac repair in the spiny mouse (Acomys).

Ischemic heart disease and by extension myocardial infarction is the primary cause of death worldwide, warranting regenerative therapies to restore heart function. Current models of natural heart regeneration are restricted in that they are not of adult mammalian origin, precluding the study of class-specific traits that have emerged throughout evolution, and reducing translatability of research findings to humans. Here, we present the spiny mouse (Acomys spp.), a murid rodent that exhibits bona fide regeneration of the back skin and ear pinna, as a model to study heart repair. By comparing them to ordinary mice (Mus musculus), we show that the acute injury response in spiny mice is similar, but with an associated tolerance to infarction through superior survivability, improved ventricular conduction, and near-absence of pathological remodeling. Critically, spiny mice display increased vascularization, altered scar organization, and a more immature phenotype of cardiomyocytes, with a corresponding improvement in heart function. These findings present new avenues for mammalian heart research by leveraging unique tissue properties of the spiny mouse.

A Comparison Study of Coronavirus Disease 2019 Outcomes in Hospitalized Kidney Transplant Recipients.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect any human host, but kidney transplant recipients (KTR) are considered more susceptible on the basis of previous experience with other viral infections. We evaluated rates of hospital complications between SARS-CoV-2-positive KTR and comparator groups. Methods: We extracted data from the electronic health record on patients who were hospitalized with SARS-CoV-2, testing at six hospitals from March 4 through September 9, 2020. We compared outcomes between SARS-CoV-2-positive KTR and controls: SARS-CoV-2-positive non-KTR, SARS-CoV-2-negative KTR, and SARS-CoV-2-negative non-KTR. Results: Of 31,540 inpatients, 3213 tested positive for SARS-CoV-2. There were 32 SARS-CoV-2-positive and 224 SARS-CoV-2-negative KTR. SARS-CoV-2-positive KTR had higher ferritin levels (1412; interquartile range, 748-1749 versus 553; interquartile range, 256-1035; P<0.01) compared with SARS-CoV-2-positive non-KTR. SARS-CoV-2-positive KTR had higher rates of ventilation (34% versus 14%, P<0.01; versus 9%, P<0.01; versus 5%, P<0.01), vasopressor use (41% versus 16%, P<0.01; versus 17%, P<0.01; versus 12%, P<0.01), and AKI (47% versus 15%, P<0.01; versus 23%, P<0.01; versus 10%, P<0.01) compared with SARS-CoV-2-positive non-KTR, SARS-CoV-2-negative KTR, and SARS-CoV-2-negative non-KTR, respectively. SARS-CoV-2-positive KTR continued to have increased odds of ventilation, vasopressor use, and AKI compared with SARS-CoV-2-positive non-KTR independent of Elixhauser score, Black race, and baseline eGFR. Mortality was not significantly different between SARS-CoV-2-positive KTR and non-KTR, but there was a notable trend toward higher mortality in SARS-CoV-2-positive KTR (25% versus 16%, P=0.15, respectively). Conclusions: Hospitalized SARS-CoV-2-positive KTR had a high rate of mortality and hospital complications, such as requiring ventilation, vasopressor use, and AKI. Additionally, they had higher odds of hospital complications compared with SARS-CoV-2-positive non-KTR after adjusting for Elixhauser score, Black race, and baseline eGFR. Future studies with larger sample size of KTR are needed to validate our findings. Podcast: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/K360/2021_03_25_KID0005652020.mp3.

Identifying a Kidney Transplant Recipient COVID Phenotype to Aid Test Utilization in the Setting of Limited Testing Availability-Does One Exist?

The high morbidity and mortality of COVID-19 in immunocompetent patients raises significant concern for immunosuppressed kidney transplant recipients (KTRs). This level of concern, both on the part of the KTRs and transplant professionals, is heightened by a lack of prior knowledge on how Severe Acute Respiratory Syndrome 2 virus (SARS-CoV-2) may manifest differently in immunosuppressed patients. Characterizing how KTRs may present differently than the general population would allow for more targeted and timely evaluation and treatment of KTRs with COVID-19 infection. METHODS: Without prior knowledge of how this virus would affect our transplant center's delivery of care to KTRs who are SARS-CoV-2 positive or patients under investigation, and in the setting of limited testing availability, we initiated a quality assurance and improvement project (QAPI) to track KTRs followed at our transplant center through the SARS-CoV-2 testing process. RESULTS: Of the 53 symptomatic patients, 20 (38%) tested positive for SARS-CoV-2 either on presentation to the emergency department or referral to a designated outpatient testing center. In addition, 16 (80%) of the 20 patients who tested positive required inpatient treatment. Intriguingly, patients with a history of polyoma BK viremia (BKV) had a higher incidence of testing positive for SARS-CoV-2 compared to patients without a history of BKV (80% and 28%, respectively; P = .002). The Positive Predictive Value and Likelihood ratio was 80% and 6.6 for this association, respectively. Among our KTRs tested, those receiving belatacept had a lower likelihood of testing positive for SARS-CoV-2. This finding approached, but did not achieve, statistical significance (P = .06).

Spatio-temporal regulation of concurrent developmental processes by generic signaling downstream of chemokine receptors.

Chemokines are secreted proteins that regulate a range of processes in eukaryotic organisms. Interestingly, different chemokine receptors control distinct biological processes, and the same receptor can direct different cellular responses, but the basis for this phenomenon is not known. To understand this property of chemokine signaling, we examined the function of the chemokine receptors Cxcr4a, Cxcr4b, Ccr7, Ccr9 in the context of diverse processes in embryonic development in zebrafish. Our results reveal that the specific response to chemokine signaling is dictated by cell-type-specific chemokine receptor signal interpretation modules (CRIM) rather than by chemokine-receptor-specific signals. Thus, a generic signal provided by different receptors leads to discrete responses that depend on the specific identity of the cell that receives the signal. We present the implications of employing generic signals in different contexts such as gastrulation, axis specification and single-cell migration.

Brugada Syndrome in a Patient with Vascular Ehlers-Danlos Syndrome: Sudden Death Risk Amplified.

The vast majority of sudden cardiac arrests occur in patients with structural heart disease and in approximately 10% of the cases, it can occur in those with structurally normal hearts. Brugada syndrome is an autosomal dominant sodium channelopathy that has been implicated in sudden deaths. Given their low prevalence, our knowledge about Brugada syndrome is still evolving. Apart from schizophrenia, there have been no reports of associated medical conditions. We recently encountered a patient with vascular Ehlers-Danlos syndrome who was also found to have Brugada syndrome. Both these conditions share some common clinical presentations including a propensity for sudden death.

Kansas City Cardiomyopathy Questionnaire Utility in Prediction of 30-Day Readmission Rate in Patients with Chronic Heart Failure.

Background. Heart failure (HF) is one of the most common diagnoses associated with hospital readmission. We designed this prospective study to evaluate whether Kansas City Cardiomyopathy Questionnaire (KCCQ) score is associated with 30-day readmission in patients hospitalized with decompensated HF. Methods and Results. We enrolled 240 patients who met the study criteria. Forty-eight (20%) patients were readmitted for decompensated HF within thirty days of hospital discharge, and 192 (80%) patients were not readmitted. Compared to readmitted patients, nonreadmitted patients had a higher average KCCQ score (40.8 versus 32.6, P = 0.019) before discharge. Multivariate analyses showed that a high KCCQ score was associated with low HF readmission rate (adjusted OR = 0.566, P = 0.022). The c-statistic for the base model (age + gender) was 0.617. The combination of home medication and lab tests on the base model resulted in an integrated discrimination improvement (IDI) increase of 3.9%. On that basis, the KCQQ further increased IDI of 2.7%. Conclusions. The KCCQ score determined before hospital discharge was significantly associated with 30-day readmission rate in patients with HF, which may provide a clinically useful measure and could significantly improve readmission prediction reliability when combined with other clinical components.

The Hidden Culprit in a Massive Episode of Hematemesis: A Dieulafoy's Lesion.

A Dieulafoy's lesion is described as a tortuous, dilated aberrant submucosal vessel that can penetrate through the mucosa and rupture spontaneously, resulting in severe gastrointestinal bleeding. The lesion is most commonly found in the proximal stomach. Historically, it has had up to an 80% mortality rate because of its tendency to cause intermittent but severe bleeding and diagnostic challenges. We report a case of a young male with recurrent severe upper gastrointestinal bleeding with extensive prior investigations failing to reveal the source of bleeding. Computed tomography angiography of the abdomen correctly identified Dieulafoy's lesion of the stomach, and it was subsequently confirmed and successfully treated with interventional radiology (IR)-guided mesenteric angiography and embolization.