Cell-free DNA for the detection of kidney allograft rejection

Donor-derived cell-free DNA (dd-cfDNA) is an emerging noninvasive biomarker that has the potential to detect allograft injury. The capacity of dd-cfDNA to detect kidney allograft rejection and its added clinical value beyond standard of care patient monitoring is unclear. We enrolled 2,882 kidney allograft recipients from 14 transplantation centers in Europe and the United States in an observational population-based study. The primary analysis included 1,134 patients. Donor-derived cell-free DNA levels strongly correlated with allograft rejection, including antibody-mediated rejection (P \u3c 0.0001), T cell-mediated rejection (P \u3c 0.0001) and mixed rejection (P \u3c 0.0001). In multivariable analysis, circulating dd-cfDNA was significantly associated with allograft rejection (odds ratio 2.275; 95% confidence interval (CI) 1.902-2.739; P \u3c 0.0001) independently of standard of care patient monitoring parameters. The inclusion of dd-cfDNA to a standard of care prediction model showed improved discrimination (area under the curve 0.777 (95% CI 0.741-0.811) to 0.821 (95% CI 0.784-0.852); P = 0.0011) and calibration. These results were confirmed in the external validation cohorts (n = 1,748) including a cohort of African American patients (n = 439). Finally, dd-cfDNA showed high predictive value to detect subclinical rejection in stable patients. Our study provides insights on the potential value of assessing dd-cfDNA, in addition to standard of care monitoring, to improve the detection of allograft rejection. ClinicalTrials.gov registration: NCT05995379

Thrombotic microangiopathy following onasemnogene abeparvovec for spinal muscular atrophy: A case series

Spinal muscular atrophy is treated with onasemnogene abeparvovec, which replaces the missing survival motor neuron 1 gene via an adeno-associated virus vector. As of July 1, 2020, we had identified 3 infants who developed thrombotic microangiopathy following onasemnogene abeparvovec. Early recognition and treatment of drug-induced thrombotic microangiopathy may lessen mortality and morbidity

Rising Internet Shutdowns in India: A Legal Analysis

The central theme of this paper is to critically study the interplay of internet shutdowns with the right to freedom of speech and expression. A study of this nature is necessitated by India’s abysmal record with inter- net shutdowns. We must hence begin examining Internet shutdowns seriously within the Indian constitutional framework. In the recent judgment of Anuradha Bhasin, the Supreme Court has accepted that Article 19(1)(a) protects the right to disseminate and receive information through the internet. Therefore, the constitutional validity of every internet shutdown would have to be tested (at least) against the three standards ordinarily applied to test restrictions on the freedom of speech. Accordingly, this paper sequentially analyzes internet shutdowns against these three requirements. Part I of this paper addresses the lawfulness prong by studying the statutory regime that is used by the executive to impose internet shutdowns. The Telegraph Act, 1885 (and the rules framed thereunder), the Code of Criminal Procedure, 1973, and the Information Technology (Amendment) Act, 2008 (and the rules framed thereunder) are studied and compared. Part II explores the meaning of public order, which is the most relevant ground from the list given in Article 19(2) in the context of internet shutdowns. Part III explains the concept of reasonableness, which is the final requirement of Article 19(2). Part IV examines judgments in which the Indian Supreme Court and various High Courts have considered the validity of internet shutdowns and applied (or failed to apply) the relevant constitutional principles

Physician knowledge, attitudes, and practices regarding physical activity restrictions in pediatric hemodialysis patients

INTRODUCTION: Epidemiologic studies of physical activity among pediatric hemodialysis (HD) patients are lacking. A sedentary lifestyle in End-Stage Kidney Disease is associated with a higher cardiovascular mortality risk. In those patients receiving HD, time spent on dialysis and restrictions on physical activity due to access also contribute. No consensus exists regarding physical activity restrictions based on vascular access type. The aim of this study was to describe the patterns of physical activity restrictions imposed by pediatric nephrologists on pediatric HD patients and to understand the basis for these restrictions. METHODS: We conducted a cross-sectional study involving US pediatric nephrologists using an anonymized survey through Pediatric Nephrology Research Consortium. The survey consisted of 19 items, 6 questions detailed physician characteristics with the subsequent 13 addressing physical activity restrictions. FINDINGS: A total of 35 responses (35% response rate) were received. The average years in practice after fellowship was 11.5 years. Significant restrictions were placed on physical activity and water exposure. None of the participants reported accesses damage or loss that was attributed to physical activity and sport participation. Physicians practice is based on their personal experience, standard practice at their HD center, and clinical practices they were taught. DISCUSSION: There is no consensus among pediatric nephrologists about allowable physical activity in children receiving HD. Due to the lack of objective data, individual physician beliefs have been utilized to restrict activities in the absence of any deleterious effects to accesses. This survey clearly demonstrates the need for more prospective and detailed studies to develop guidelines regarding physical activity and dialysis access in order to optimize quality of care in these children

Late first acute rejection in pediatric kidney transplantation: A North American Pediatric Renal Trials and Collaborative Studies special study

Rates of early AR in pediatric kidney transplantation have declined in every era but the most recent NAPRTCS cohort has shown an increase in late first AR rates. We hypothesized this was due to an increased proportion of deceased donor utilization and early steroid taper utilization. Using the NAPRTCS database, we compared the most recent three cohorts of patients transplanted between 2002-2006, 2007-2011, and 2012-2017. To determine variables that predict late first AR, we used two multivariable models: a standard Cox regression model and LASSO model. From the LASSO model, deceased donor source (P = .002), higher recipient age (P = .019), black race (P = .010), and transplant cohort 2012-17 (P = .014) were all significant predictors of more late first AR. On standard Cox regression analysis, those same variables, minus donor source, were significant, in addition to mycophenolates usage (P = .007) and lower eGFR at 12 months (P = .02). The most recent 2012-2017 cohort remains an independently significant risk factor for late first AR, suggesting unmeasured variables. Further research is needed to determine whether these higher late first AR rates will impact long-term graft survival in the most recent cohort

Donor-derived ehrlichiosis: two clusters following solid organ transplantation

Ehrlichiosis has been infrequently described as transmissible through organ transplantation. Two donor derived clusters of ehrlichiosis are described here. During the summer of 2020, two cases of ehrlichiosis were reported to the Organ Procurement and Transplantation Network (OPTN) and the Centers for Disease Control and Prevention (CDC) for investigation. Additional transplant centers were contacted to investigate similar illness in other recipients and samples were sent to CDC. Two kidney recipients from a common donor developed fatal ehrlichiosis-induced hemophagocytic lymphocytic histiocytosis (HLH). Two kidney recipients and a liver recipient from another common donor developed ehrlichiosis. All three were successfully treated. Clinicians should consider donor-derived ehrlichiosis when evaluating recipients with fever early after transplantation after more common causes are ruled out, especially if the donor has epidemiological risk factors for infection. Suspected cases should be reported to the organ procurement organization (OPO) and the OPTN for further investigation by public health authorities