Outcomes of short-duration antiviral prophylaxis for hepatitis C positive donor kidney transplants.

Trials describing 4- to 12-week courses of direct-acting antiviral drugs (DAAs) to treat hepatitis C virus (HCV) transmission from infected donors to uninfected kidney transplant recipients (D+/R- transplants) may be limited in "real-world" application by costs and delayed access to DAAs. We previously reported HCV transmission of 13% among D+/R- transplants with 2- to 4-day pangenotypic sofosbuvir/velpatasvir (SOF/VEL) perioperative prophylaxis, where one patient with HCV transmission was a nonresponder to first-line full-course DAA. Here, we report new data with a 7-day prophylaxis protocol (N = 50), as well as cumulative treatment and outcome data on all HCV D+/R- transplants (N = 102).

Correlation of Donor-derived Cell-free DNA With Histology and Molecular Diagnoses of Kidney Transplant Biopsies.

Background: Circulating donor-derived cell-free DNA (cfDNA), a minimally invasive diagnostic tool for kidney transplant rejection, was validated using traditional histology. The molecular microscope diagnostic system (MMDx) tissue gene expression platform may provide increased precision to traditional histology.

Methods: In this single-center prospective study of 208 biopsies (median = 5.

Coronavirus Disease 2019 Viremia, Serologies, and Clinical Course in a Case Series of Transplant Recipients.

Here we report a single-center cohort of 6 patients (4 kidney only, and 2 simultaneous liver/kidney transplants) diagnosed with COVID-19 at a median of 1.9 years (range = 0.2-9.

Elevated AT1R Antibody and Morbidity in Patients Bridged to Heart Transplant Using Continuous Flow Left Ventricular Assist Devices.

Background: We studied longitudinal levels of angiotensin-II type 1 receptor antibody (AT1R-Ab) and their effects on adverse events (death, treated rejection and cardiac allograft vasculopathy) in patients who were bridged to heart transplant using a continuous flow left ventricular assist device (LVAD).

Methods And Results: Sera of 77 patients bridged to heart transplant (from 2009 to 2017) were tested for AT1R-Ab and CRP before and after LVAD. Elevated AT1R-Ab was defined as >10.

Impact of Belatacept Conversion on Renal Function, Histology, and Gene Expression in Kidney Transplant Patients With Chronic Active Antibody-mediated Rejection.

Background: Here, we present our initial experience with a prospective protocol of belatacept conversion in patients with chronic active antibody-mediated rejection (caAMR) and a high degree of chronicity at the time of diagnosis.

Methods: We converted 19 patients (mean age, 45 ± 12 y) with biopsy-proven caAMR from tacrolimus to belatacept at a median of 44 months post-kidney transplant.

Results: At a median of 29 months (interquartile range, 16-46 mo) postconversion, death-censored graft and patient survivals were 89% and 95%, respectively.

Lack of Histological and Molecular Signature Response to Tocilizumab in Kidney Transplants with Chronic Active Antibody Mediated Rejection: A Case Series.

Background: Traditional therapies for caAbMR have unclear efficacy with significant side effects in recipients of kidney transplants (KTs). A recent single-center case series suggested tocilizumab (TCZ) could stabilize renal function and improve microvascular inflammation. Here we report our findings of the use of TCZ in patients with caAbMR.

Killer Immunoglobulin-Like Receptor-Ligand Interactions Predict Clinical Outcomes following Unrelated Donor Transplantations.

Killer immunoglobulin-like receptor (KIR) and KIR ligand (KIRL) interactions play an important role in natural killer (NK) cell-mediated graft-versus-leukemia effect following hematopoietic cell transplantation (HCT). However, there is considerable heterogeneity in the KIR gene and KIRL content in individuals, making it difficult to estimate the full clinical impact of NK cell reconstitution following HCT. Here we present a novel adaptive mathematical model designed to quantify these interactions to better assess the influence of NK cell-mediated alloreactivity on transplant outcomes.

Ultra-short duration direct acting antiviral prophylaxis to prevent virus transmission from hepatitis C viremic donors to hepatitis C negative kidney transplant recipients.

We conducted an adaptive design single-center pilot trial between October 2017 and November 2018 to determine the safety and efficacy of ultra-short-term perioperative pangenotypic direct acting antiviral (DAA) prophylaxis for deceased hepatitis C virus (HCV)-nucleic acid test (NAT) positive donors to HCV negative kidney recipients (D+/R-). In Group 1, 10 patients received one dose of SOF/VEL (sofusbuvir/velpatasvir) pretransplant and one dose on posttransplant Day 1. In Group 2A (N = 15) and the posttrial validation (Group 2B; N = 25) phase, patients received two additional SOF/VEL doses (total 4) on Days 2 and 3 posttransplant.

Antibody mediated rejection due to de-novo DSA causing venous thrombosis of pancreas allograft - A case report.

This case describes a 34year old female who underwent an HLA identical living donor kidney transplant with a positive flow cytometric crossmatch (FCXM), but without any donor specific antibody (DSA). Tests to detect non-HLA antibody and autoantibody were negative. Allograft functioned well without rejection.

Circulating angiotensin type II receptor: Possible marker for antibody mediated rejection after renal transplantation?

Background: Presence of antibody [Ab] against angiotensin receptor [AT1R] indicates heightened risk for antibody mediated rejection [AMR] after transplantation but is insufficient as a marker. We speculated AT1R might be released systemically because of AMR and might be a useful biomarker.

Methods: AT1R was measured in blood from 73 Normals and 72 renal patients pre- and post-transplantation.

Perioperative Desensitization Improves Outcomes Among Crossmatch Positive Recipients of Deceased Donor Renal Transplants.

Context: Graft failure due to chronic rejection is greater among renal transplant patients with donor-specific antibody (DSA) than among DSA-free patients. For patients dependent on deceased donor transplantation, preoperative desensitization to eliminate DSAs may be impractical. We speculated that perioperative desensitization might eliminate preexisting DSAs and prevent de novo DSAs and improve graft outcomes.

Pre-transplant phospholipase A2 receptor autoantibody concentration is associated with clinically significant recurrence of membranous nephropathy post-kidney transplantation.

Previous studies that have assessed the association of pre-transplant antiphospholipase A2 receptor autoantibody (PLA2R-Ab) concentration with a recurrence of membranous nephropathy (rMN) post-kidney transplant have yielded variable results. We tested 16 consecutive transplant patients with a history of iMN for pre-transplant PLA2R-Ab. Enzyme-linked immunosorbent assay titers (Euroimmun, NJ, USA) >14 RU/mL were considered positive.

Post-transplant Desensitization for Deceased Donor Kidney Transplant Recipients: A Single Center Experience.

The highly-sensitized kidney transplant candidate with no available living donors remains at a major disadvantage with decreased access and worse outcomes post-transplant. We have previously reported our initial data on both pre-transplant and post-transplant desensitization. We observed only a modest decline in unacceptable antigens with pretransplant intravenous immunoglobin (IVIG) and rituximab.

Pregnancy-related allograft rejection following heart transplant.

Current recommendations do not discourage pregnancy in stable, orthotopic heart transplant (OHT) recipients who are more than 1 year posttransplant, although a highly specialized level of care with a multidisciplinary team is recommended. These patients may incur significant risk to themselves, their allograft, and/or their fetuses. Recognition and treatment of posttransplant complications in pregnancy also may be difficult.

Effects of Two Preemptive Post-transplant Desensitization Regimens Upon Renal Allograft Survival and DSA Elaboration.

We used a simple point-based algorithm to identify patients who might benefit from desensitization because of their higher risk of antibody-mediated chronic rejection and graft failure. Points were assigned to known but easily determined risk factors (panel reactive antibody, flow crossmatch, delayed graft function) and calculated immediately after deceased donor kidney transplantation. Point totals were used to identify: 1) which patients would receive desensitization; and, 2) which regimen each patient would receive.

Graft-versus-host disease after solid organ transplantation: a single center experience and review of literature.

Background: Graft-versus-host disease (GVHD) is an uncommon cause of morbidity and mortality after solid organ transplantation that is most likely under-diagnosed. We describe our single center experience with three cases of GVHD diagnosed over a period of 15 years in a total of 2,271 solid organ transplant recipients.

Case Reports: We describe three case reports: (1) a 3-week old neonate who developed GVHD 16 months after living-related liver transplant, (2) a 14-year old adolescent who developed GVHD 4 months following an unrelated cadaveric pancreas transplant and; (3) a 27-year old male who developed GVHD 18 days after simultaneous kidney-pancreas transplant from an unrelated donor.

Surveillance of alloantibodies after transplantation identifies the risk of chronic rejection.

The monitoring of the levels of alloantibodies following transplantation might facilitate early diagnosis of chronic rejection (CR), the leading cause of renal allograft failure. Here, we used serial alloantibody surveillance to monitor patients with preoperative positive flow cytometric crossmatch (FCXM). Sixty-nine of 308 renal transplant patients in our center had preoperative positive FCXM.

A novel post-transplant alloantibody surveillance and intervention strategy that improves graft outcomes in sensitized renal transplant recipients.

Chronic rejection, the leading cause of renal graft failure, is mediated by alloantibody graft destruction. Monitoring alloantibodies posttransplant might facilitate early diagnosis of alloantibody mediated graft destruction and provide an opportunity for intervention. Herein, we describe our alloantibody surveillance and intervention protocol that has improved graft survival.

Quantitation of alloantibody concentration can predict patient sensitivity to intravenous immunoglobulin desensitization.

Despite the success of intravenous immunoglobulin (IVIg) desensitization to reduce anti-human leukocyte antigen antibodies, its high failure rate and expense limit its usefulness. We speculated that quantitation of alloantibody concentration could allow early identification of IVIg resistant patients. Patients were described as nonresponders (n=3) or responders (n=8).

Living donor liver transplant with clinical tolerance, laboratory evidence of chimerism, and spontaneous clearance of HBV.

We present a case of functional and histopathologic tolerance, chimerism, and spontaneous clearance of HBV in a patient four years after living donor liver transplant (LDLT). A 19-year-old male patient underwent a LDLT for HBV cirrhosis. He voluntarily ceased immunosuppression and antiviral therapy after 6 months.