BACKGROUND: Despite improvements in access to transplantation, there remains disparities in all aspects of transplant among minority patients. We sought to examine referral practices and long-term outcomes of kidney transplantation across racial identities at our center. STUDY DESIGN: We conducted a retrospective review of kidney transplantation recipients from January 2010 to May 2024. Data were obtained from United Network for Organ Sharing and confirmed with the electronic medical record. Patients were categorized as White, Black, Asian, Hispanic, Hawaiian/Pacific Islander, and American Indian/Alaska Native. RESULTS: A total of 1,369 patients met criteria with 67% White, 6.9% Black, 7.9% Asian, 14.1% Hispanic, 2.6% Hawaiian/Pacific Islander, and 1.5% American Indian/Alaska Native. There were no significant between group differences in kidney donor profile index, expected posttransplant survival, recipient or donor age or cytomegalovirus status, cold ischemia time, and time from referral to evaluation or listing. There was a significant difference in waiting time for Black compared with White patients (733.6 vs 595.4 days, p = 0.026). Black patients had higher mean creatinine at 6 months and 1 year compared with all others (1.6 vs 1.3 mg/dL at both time points, p < 0.001). After adjusting for baseline characteristics, Black patients had an increased risk of allograft loss at 15 years compared with White patients (p < 0.001) and were to receive a living donor transplant (10.5% vs 25.3%, p < 0.01) or a preemptive kidney transplantation (10.5% vs 27.0%, p < 0.01). CONCLUSIONS: Despite disproportionate representation among patients with chronic kidney disease, compared with age-matched White patients, Black patients at our center are referred for transplant later and have a higher rate of 10-year allograft loss. It is up to us to focus on education and close the gap and improve outcomes for all of our transplant recipients.

Environmental nephrotoxins include materials found predominantly in the workplace. The clinically important industrial nephrotoxins include lead, mercury, cadmium, silica, a variety of organic hydrocarbons, uranium, chromium, and arsenic. Fanconi syndrome has been reported in children with acute lead toxicity. Exposure to mercury can be through inhalation, oral, or dermal. After exposure to a toxic dose of mercury exposure, mitochondrial swelling and dilation of the endoplasmic reticulum of proximal tubular cell can be identified. Once cadmium is absorbed systemically, it accumulates in multiple organs, including bone and liver, like other heavy metals, but also in the kidney. Halogenated hydrocarbons have often been implicated in the induction of acute tubular necrosis or Fanconi syndrome in both humans and experimental animals. Initially, solvent nephropathy was associated with antiglomerular basement membrane antibody-mediated glomerulonephritis and pulmonary haemorrhage but later reports of solvent nephropathy have included many different types of glomerulonephritis.

BACKGROUND:The development of cytomegalovirus (CMV) infection after kidney transplant remains a significant cause of posttransplant morbidity, graft loss, and mortality. Despite appropriate antiviral therapy, recipients without previous CMV exposure can currently be allocated a kidney from a donor with previous CMV infection (D+R-) that carries the greatest risk of posttransplant CMV infection and associated complications. Preferential placement of CMV D- organs in negative recipients (R-) has been shown to reduce the risk of viral infection and associated complications. METHODS:To assess the long-term survival and economic benefits of allocation policy reforms, a decision-analytic model was constructed to compare receipt of CMV D- with CMV D+ organ in CMV R- recipients using data from transplant registry, Medicare claims, and pharmaceutical costs. RESULTS:For CMV R- patients, receipt of a CMV D- organ was associated with greater average survival (14.3 versus 12.6 y), superior quality-adjusted life years (12.6 versus 9.8), and lower costs ($529 512 versus $542 963). One-way sensitivity analysis demonstrated a survival advantage for patients waiting as long as 30 mo for a CMV D- kidney. CONCLUSIONS:Altering national allocation policy to preferentially offer CMV D- organs to CMV R- recipients could improve survival and lower costs after transplant if appropriately implemented.

Objective: To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). Summary of Background Data: In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate. Methods: The United States HCC LT Consortium (2015–2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS). Results: Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0–3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0–3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01). Conclusions: The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results.

The American Society of Echocardiography is composed of health care providers and scientists committed to the well-being of patients through excellence in cardiovascular imaging. In alignment with the society's mission to provide education that improves clinical outcomes, this consensus statement has been generated to provide our members and all practitioners of echocardiography with information and recommendations that will benefit the safety of patients receiving ultrasound enhancing agents (UEAs). Specifically, this document provides expert opinion on the clinical impact of the recent alert from MedWatch, the US Food and Drug Administration (FDA) product safety reporting system, on presumed type I immediate hypersensitivity reactions to the polyethylene glycol (PEG) component of UEAs. The UEAs that are approved for use by the FDA include perfluorocarbon or sulfur hexafluoride microbubbles stabilized with 'shells"composed of albumin or lipid.1 These agents can interact with immune cells of the monocytic/phagocytic system via opsonization involving the complement (C0) system or interaction with specific immune cell surface receptors.2 These interactions contribute to the normal and uneventful mechanism for clearance of UEAs from the circulation by the reticuloendothelial (mononuclear phagocyte) system. Serious immune-related reactions to UEAs are rare and have been attributed largely to C0 activation-related pseudoallergy reactions, which are known to also occur with liposomal drug preparations.1,3-6 The lipid-based UEAs approved for human use by the FDA contain PEG either in the excipient (vehicle or inactive ingredient) alone (Lumason and SonoVue; Bracco Diagnostics, Milan, Italy) or in the microbubble shell and the lipid excipient (Definity, Definity RT, and Luminity; Lantheus Medical Imaging, North Billerica, MA). The PEG components not only stabilize the agents but when incorporated in the shell can also reduce microbubble opsonization and interaction with cells.7 The potential for rare immunoglobulin E-mediated type I hypersensitivity reactions to PEG components has been recently recognized after publication of case reports implicating PEG allergy.8,9 The MedWatch alert is based on post marketing pharmacovigilance from more than two decades that identified 11 cases of anaphylaxis, including two deaths, related to the administration of UEAs in patients with preexisting PEG hypersensitivity. The comments below provide expert opinion on the impact of newly recognized PEG hypersensitivity. We believe that it is important to recognize the potential for reactions to the PEG component of lipid UEAs. Our recommendations also take into account that these reactions remain extremely rare and that UEAs provide vital information that improves patient outcomes arising from the ability of UEAs to detect or exclude life-threatening conditions or to stratify patients to lifesaving therapies.1

SummaryNew-onset diabetes after transplantation (NODAT) is increasing in frequency and creates many challenges directly impacting the patient and graft survival. Most transplant programs offer a fixed-dose prednisone taper schedule for the prevention of acute rejection following kidney transplantation. In this study, we investigated the incidence of NODAT in new kidney transplant recipients.MethodsThis was a retrospective, single-center study assessing rates of NODAT according to age, ethnicity, body weight, BMI, rejection, and prednisone dosing among kidney transplant recipients.ResultsAmong non-diabetic consecutive kidney transplant recipients (n = 261) from 1/2014 to 12/2018, a total of 47 (18%) kidney transplant recipients developed NODAT. After adjusting for common NODAT risk factors, analysis of the population indicated that age, and corticosteroid dose in the Asian American population [adjusted for lower body weight, BMI] significantly increased the risk of NODAT. In multi-variance analysis, despite receiving lower standard doses of protocol corticosteroid daily, when adjusted for actual body weight (mg/kg/day) Asian American recipients had high incidence of NODAT compared to other ethnicity. Asian American received higher doses or corticosteroids (prednisone) than non-Asian Americans (0.14 mg/kg vs. 0.11 mg/kg) (p = 0.008). The overall incidence of rejection was not higher among those who developed NODAT (p = 0.55)ConclusionThis is the first study to explore the relationship between corticosteroid dose and diabetes in Asian Americans. Asian Americans had higher rates of NODAT and received higher doses of weight-based corticosteroids. There is a possible iatrogenic, pharmacogenomic, and addressable etiology to NODAT in this population.

Graft-versus-host disease after liver transplantation (LT-GVHD) is rare, frequently fatal, and associated with bone marrow failure (BMF), cytopenias, and hyperferritinemia. Given hyperferritinemia and cytopenias are present in hemophagocytic lymphohistiocytosis (HLH), and somatic mutations in hematopoietic cells are associated with hyperinflammatory responses (clonal hematopoiesis of indeterminate potential, CHIP), we identified the frequency of hemophagocytosis and CHIP mutations in LT-GVHD. We reviewed bone marrow aspirates and biopsies, quantified blood/marrow chimerism, and performed next-generation sequencing (NGS) with a targeted panel of genes relevant to myeloid malignancies, CHIP, and BMF. In all, 12 marrows were reviewed from 9 LT-GVHD patients. In all, 10 aspirates were evaluable for hemophagocytosis; 7 had adequate DNA for NGS. NGS was also performed on marrow from an LT cohort (n = 6) without GVHD. Nine of 10 aspirates in LT-GVHD patients showed increased hemophagocytosis. Five (71%) of 7 with LT-GVHD had DNMT3A mutations; only 1 of 6 in the non-GVHD LT cohort demonstrated DNMT3A mutation (p = .04). Only 1 LT-GVHD patient survived. BMF with HLH features was associated with poor hematopoietic recovery, and DNMT3A mutations were over-represented, in LT-GVHD patients. Identification of HLH features may guide prognosis and therapeutics. Further studies are needed to clarify the origin and impact of CHIP mutations on the hyperinflammatory state.

Background: Alemtuzumab, an antilymphocyte (anti-CD52) monoclonal antibody, has been shown to be at least equivalent in efficacy compared to standard induction therapy in preventing acute rejection at one year post-transplantation, but is associated with three major categories of risk: increased susceptibility to infection, increased risk of lymphoproliferative malignancy, as well as a more acute risk of infusion-related reaction that can range widely in severity from mild fever to full cytokine release syndrome that is more likely to occur during the first dose. Alemtuzumab is more typically chosen for induction in high immunologic risk kidney recipients and in cases of delayed graft function at some transplant centers. However, its safety when used for delayed graft function has not been directly compared to other immunosuppressive agents, and the incidence of cytokine release syndrome from alemtuzumab or other lymphocyte-depleting agents is not known. Case Presentation: We present two cases of flash pulmonary edema due to cytokine release syndrome in two kidney transplant recipients who received alemtuzumab for delayed graft function. In one case, dialysis was performed prior to alemtuzumab administration, while in the other case, euvolemia was already established by dialysis prior to the drug administration. Conclusion: Cytokine release syndrome is an underappreciated risk from alemtuzumab. In our discussion, we illuminate the risks and propose preventive measures.

Cytomegalovirus (CMV) is a major cause of infection-related morbidity and mortality in kidney transplantation. The most significant risk for developing CMV infection after transplant depends upon donor (D) and recipient (R) CMV serostatus. In 2012, our Organ Procurement Organization (OPO) began a novel pretransplant CMV prevention strategy via matching deceased kidney donors and recipients by CMV serostatus. Prior to the matching protocol, our distribution of seropositive and seronegative donors and recipients was similar to the United States at large. After the matching protocol, high-risk D+R- were reduced from 18.5% to 2.9%, whereas low-risk D-R- were increased from 13.5% to 24%. There was no adverse effect on transplant rates and no differential effect on waiting times for R+ vs R- after the protocol was implemented. This protocol could be implemented on a regional or national level to optimize low and high-risk CMV seroprofiles and potentially improve CMV-related outcomes in kidney transplantation.

Thrombotic microangiopathy (TMA) is a recognized and serious complication of renal transplantation. Atypical hemolytic uremic syndrome (aHUS), a subset of TMA, occurs in the setting of dysregulation of the alternative complement pathway and can cause disease in native kidneys as well as recurrence in allografts. De novo TMA represents a classification of TMA post-transplant in the absence of clinical or histopathological evidence of TMA or aHUS in the native kidney. De novo TMA is a more heterogeneous syndrome than aHUS and the pathogenesis and risk factors for de novo TMA are poorly understood. The association between calcineurin inhibitors (CNI) and de novo TMA is controversial. Anti-complement blockade therapy with eculizumab is effective in some cases, but more studies are needed to identify appropriate candidates for therapy. We present two cases of de novo TMA occurring immediately in recipients from the same deceased donor and provoking the question of whether deceased donor-related factors could represent risks for developing de novo TMA.

Cardiovascular disease (CVD) continues to be the leading cause of death in Western civilizations, and hyperlipidemia is a well-established independent risk factor for the development of atherosclerosis and CVD progression. Many chronic kidney disease (CKD) and dialysis patients have the traditional CVD risk factors (age, obesity, hypertension, diabetes mellitus, and hyperlipidemia); however, CKD and dialysis predispose patients to several non-traditional risk factors, including myocardial remodeling, hyperparathyroidism, malnutrition, bone and mineral disorders, anemia, albuminuria, inflammation, and endothelial dysfunction. Interestingly, as both cardiovascular morbidity and mortality increase and renal function declines, the therapeutic benefits of lipid-lowering agents decrease significantly. However, their recognized reduction in cardiovascular events and excellent tolerability contribute to the frequent use of lipid-lowering agents. Statins are the most commonly prescribed agents for the treatment of hyperlipidemia. Recent post hoc analyses of the lipid lowering in patients with CKD indicate that lowering low-density lipoprotein cholesterol may provide long-term cardiovascular protection in patients with CKD stages I–IV. However, questions remain regarding the optimal role of lipid-lowering agents for primary prevention in patients on dialysis. Statins remain the preferred first-line pharmacologic therapy, but non-statin add-on therapies can be used to decrease the overall risk of CVD in the CKD population, though evidence supporting each agent in CKD is limited. Finally, given the reduced glomerular filtration and drug clearance, healthcare providers should monitor their patients closely and adjust treatment goals and objectives according to patient factors, drug safety, efficacy, and cost.