Incorporation of Donor-derived Cell-free DNA Into Clinical Practice for Renal Allograft Management.

Background: Donor-derived cell-free DNA (dd-cfDNA) in plasma is an established noninvasive biomarker for allograft injury and rejection. A single-nucleotide polymorphism (SNP)-based massively multiplexed polymerase chain reaction methodology can be used to quantify dd-cfDNA in kidney transplant recipients. In this study we describe our clinical experience in using a SNP-based dd-cfDNA assay for the management of active rejection in renal transplant recipients.

Clinical Rationale for a Routine Testing Schedule Using Donor-Derived Cell-Free DNA After Kidney Transplantation.

Kidney transplant recipients require meticulous clinical and laboratory surveillance to monitor allograft health. Conventional biomarkers, including serum creatinine and proteinuria, are lagging indicators of allograft injury, often rising only after significant and potentially irreversible damage has occurred. Immunosuppressive medication levels can be followed, but their utility is largely limited to guiding dosing changes or assessing adherence.

Transplant administration-A survey of the roles and responsibilities of kidney and pancreas medical directors of US transplant centers.

The current American Society of Transplantation (AST) accredited transplant fellowship programs in the United States provide no structured formal training in leadership and administration which is essential for successfully running a transplant program. We conducted a survey of medical directors of active adult kidney and kidney-pancreas transplant programs in the United States about their demographics, training pathways, and roles and responsibilities. The survey was emailed to 183 medical directors, and 123 (67.

Liver Transplantation in Patients with Sickle Cell Disease in the United States.

Background: Up to 30% of patients with sickle cell disease (SCD) develop chronic liver disease via etiologies including sickle cell hepatopathy, acquired viral hepatitis, or secondary hemochromatosis. It is unclear how many patients with SCD ultimately undergo liver transplantation (LT) and what factors are associated with survival after LT. In this study, we examined LT outcomes in these patients by reviewing the Scientific Registry of Transplant Recipients (SRTR) and our institutional experience.

High levels of dd-cfDNA identify patients with TCMR 1A and borderline allograft rejection at elevated risk of graft injury.

The clinical importance of subclinical, early T cell-mediated rejection (Banff TCMR 1A and borderline lesions) remains unclear, due, in part to the fact that histologic lesions used to characterize early TCMR can be nonspecific. Donor-derived cell-free DNA (dd-cfDNA) is an important molecular marker of active graft injury. Over a study period from June 2017 to May 2019, we assessed clinical outcomes in 79 patients diagnosed with TCMR 1A/borderline rejection across 11 US centers with a simultaneous measurement of dd-cfDNA.

Two-year outcomes in de novo renal transplant recipients receiving everolimus-facilitated calcineurin inhibitor reduction regimen from the TRANSFORM study.

TRANSFORM (TRANSplant eFficacy and safety Outcomes with an eveRolimus-based regiMen) was a 24-month, prospective, open-label trial in 2037 de novo renal transplant recipients randomized (1:1) within 24 hours of transplantation to receive everolimus (EVR) with reduced-exposure calcineurin inhibitor (EVR + rCNI) or mycophenolate with standard-exposure CNI. Consistent with previously reported 12-month findings, noninferiority of the EVR + rCNI regimen for the primary endpoint of treated biopsy-proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR) <50 mL/min per 1.73 m was achieved at month 24 (47.

Delayed graft function in kidney transplantation.

Purpose Of Review: Delayed graft function (DGF) has several long-term graft implications in the field of kidney transplantation and remains a challenge. The incidence of DGF is on the rise because of an increasing use of marginal kidneys in an era of organ shortage. Risk factors for DGF are numerous and stem from multiple sources in the transplant chain starting from the donor to its final allocation in the recipient.

Marginal kidney transplantation: the road less traveled.

Purpose Of Review: Kidney transplantation indisputably confers a significant survival advantage and a better quality of life compared with dialysis, however, because of the increasing demand for kidney transplantation many patients continue to wait prolonged periods for kidney transplantation. The first step to alleviate the shortage is to reduce the discard rate by utilizing more marginal kidneys. This review studied the recent literature on marginal kidney transplantation.

Everolimus with Reduced Calcineurin Inhibitor Exposure in Renal Transplantation.

Everolimus permits reduced calcineurin inhibitor (CNI) exposure, but the efficacy and safety outcomes of this treatment after kidney transplant require confirmation. In a multicenter noninferiority trial, we randomized 2037 kidney transplant recipients to receive, in combination with induction therapy and corticosteroids, everolimus with reduced-exposure CNI (everolimus arm) or mycophenolic acid (MPA) with standard-exposure CNI (MPA arm). The primary end point was treated biopsy-proven acute rejection or eGFR<50 ml/min per 1.

Kidney outcomes in patients with liver cirrhosis and chronic kidney disease receiving an orthotopic liver transplant alone.

Kidney transplant in patients with liver cirrhosis and nondialysis chronic kidney disease (CKD) is controversial. We report 14 liver cirrhotic patients who had persistently low MDRD-6 estimated glomerular filtration rate (e-GFR) <40 mL/min/1.73 m for ≥3 months and underwent either liver transplant alone (LTA; n=9) or simultaneous liver-kidney transplant (SLKT; n=5).

Duplex Doppler sonography: is there clinical relevance to elevated renal vein velocity in kidney transplants?

Purpose: This study aims to determine a velocity threshold in the main renal vein (MRV) of renal transplants and evaluate the cause and clinical significance of elevated velocity.

Methods: Maximum MRV velocity from 331 consecutive renal transplant Doppler ultrasounds in 170 patients was recorded. A priori, twice the median MRV velocity was selected as the threshold for elevation.

Bortezomib in kidney transplantation.

Purpose Of Review: The purpose of this review is to evaluate the effectiveness of bortezomib in the recent literature for the prevention and treatment of kidney transplant rejection.

Recent Findings: Several studies have analyzed bortezomib alone and in comparison to more traditional immunosuppressive agents during the last 2 years. If administered prior to transplant or soon thereafter, bortezomib appears to lower donor-specific antibody levels and improves graft survival.

Kidney transplantation in the Hispanic population.

Hispanic race and low socioeconomic status are established predictors of disparity in access to kidney transplantation. This single-center retrospective review was undertaken to determine whether Hispanic race predicted kidney transplant outcomes. A total of 720 patients underwent kidney transplantation from January 1, 2004 to December 31, 2013, including 398 Hispanic patients and 322 non-Hispanic patients.

Evaluation of a telenovela designed to improve knowledge and behavioral intentions among Hispanic patients with end-stage renal disease in Southern California.

Objectives: Culturally relevant education is needed to improve rates of successful kidney transplantation among Hispanic patients with end-stage renal disease (ESRD). This study examined whether patients' knowledge about kidney disease, postoperative care, and proactive health practices improved after watching a telenovela series about ESRD.

Design: 334 ESRD patients and 94 family members/caregivers were assigned to watch a telenovela ('Fixing Paco,' a bilingual health education film) or receive standard of care at a transplant center or at a dialysis clinic.

Strategies for the management of adverse events associated with mTOR inhibitors.

Mammalian target of rapamycin (mTOR) inhibitors are used as potent immunosuppressive agents in solid-organ transplant recipients (everolimus and sirolimus) and as antineoplastic therapies for various cancers (eg, advanced renal cell carcinoma; everolimus, temsirolimus, ridaforolimus). Relevant literature, obtained from specific PubMed searches, was reviewed to evaluate the incidence and mechanistic features of specific adverse events (AEs) associated with mTOR inhibitor treatment, and to present strategies to effectively manage these events. The AEs examined in this review include stomatitis and other cutaneous AEs, wound-healing complications (eg, lymphocele, incisional hernia), diabetes/hyperglycemia, dyslipidemia, proteinuria, nephrotoxicity, delayed graft function, pneumonitis, anemia, hypertension, gonadal dysfunction, and ovarian toxicity.

Association of interferon gamma gene polymorphisms with BK virus infection among Hispanic renal allograft recipients.

Background: BK virus nephropathy is one of the most common viral infections that affect up to 10% of renal transplant recipients (RTRs), causing allograft dysfunction and graft loss. Interferon-gamma (IFN-γ) gene polymorphisms have been associated with parvovirus B19, hepatitis C virus, HIV-1/AIDS infection, cytomegalovirus viremia, and disease. IFN-γ is known to have potent inhibitory effects on BK virus gene expression, both at the level of transcription and translation.

Genetic polymorphisms of UGT1A8, UGT1A9 and HNF-1α and gastrointestinal symptoms in renal transplant recipients taking mycophenolic acid.

Mycophenolic acid (MPA), a widely used immunosuppressant, has a complex metabolism that involves a number of enzymes. Some of its metabolites are thought to be the cause of gastrointestinal (GI) side effects. In this study, we investigated whether polymorphisms of UDP-glucuronosyltransferases (UGT1) A8, 1A9, and hepatocyte nuclear factor (HNF1α) genes or pharmacokinetic parameters of mycophenolic acid (MPA) were associated with the severity of GI symptoms in patients receiving MPA therapy.

Posttransplant malignancies in solid organ adult recipients: an analysis of the U.S. National Transplant Database.

Background: De novo posttransplant malignancy (PTM) is a serious complication of transplantation. Incidences may vary among solid organ transplantations (SOTs) and may take to particular screening recommendations and posttransplantation care.

Methods: Adult recipients, from the U.

A rapid and efficient method BK polyomavirus genotyping by high-resolution melting analysis.

A small percentage of renal patients become infected with the BK polyomavirus (BKV), a pathogenic virus that causes BKV-associated nephropathy (BKVN), after kidney transplantation. This study presents a simple, rapid, high-throughput method for BKV genotyping using high-resolution melt analysis (HRMA). Using this novel method, BKV genotypes were analyzed in 49 samples taken from BKV-positive renal transplantation patients for classification into 1 of 3 genotypes: GI-1 (subgroups Ia, Ib1, and Ic), GI-2 (subgroup Ib2), and GII-IV (subtypes II, III, and IV).

The pharmacokinetics of enteric-coated mycophenolate sodium and its gastrointestinal side effects in de novo renal transplant recipients of Hispanic ethnicity.

Objective: The aim of the study is to characterize the pharmacokinetics and the gastrointestinal side effect profiles of enteric-coated mycophenolate sodium (EC-MPS) in de novo kidney transplant patients of Hispanic ethnicity.

Materials And Methods: The pharmacokinetic study of EC-MPS was conducted in 11 de novo kidney transplant patients of Hispanic ethnicity. Eight blood samples were obtained after EC-MPS was given at the steady state.

Development of a real-time quantitative PCR assay for detection of a stable genomic region of BK virus.

Background: BK virus infections can have clinically significant consequences in immunocompromised individuals. Detection and monitoring of active BK virus infections in certain situations is recommended and therefore PCR assays for detection of BK virus have been developed. The performance of current BK PCR detection assays is limited by the existence of viral polymorphisms, unknown at the time of assay development, resulting in inconsistent detection of BK virus.

Incentivizing living organ donation.

Purpose Of Review: The number of organs available for the patients on the transplant waitlist remains at a disproportionate low. All possible methods to curtail this shortage, including providing donors with incentives, have been proposed. This article reviews recent publications addressing the benefits and risks involved in incentivizing living donation.

Costimulation targeting therapies in organ transplantation.

Purpose Of Review: Long-term side effects of posttransplant immunosuppressive agents contribute to graft loss and death. This article reviews recent publications on the potential role of costimulation targeting therapies, especially belatacept, in solid organ transplantation.

Recent Findings: Belatacept, currently undergoing phase III clinical trials in renal transplantation, has shown promise as a safe and effective alternative immunosuppression regimen to calcineurin inhibitor and steroid-based therapies.