Reversing donor-specific antibody responses and antibody-mediated rejection with bortezomib and belatacept in mice and kidney transplant recipients.

Active antibody-mediated rejection (AMR) is a potentially devastating complication and consistently effective treatment remains elusive. We hypothesized that the reversal of acute AMR requires rapid elimination of antibody-secreting plasma cells (PC) with a proteasome inhibitor, bortezomib, followed by the sustained inhibition of PC generation with CTLA4-Ig or belatacept (B/B). We show in mice that B/B therapy selectively depleted mature PC producing donor-specific antibodies (DSA) and reduced DSA, when administered after primary and secondary DSA responses had been established.

"Early" and "Late" Hospital readmissions in the first year after kidney transplant at a single center.

Background: Hospital readmission (HR) after surgery is considered a quality metric.

Methods: Data on 2371 first-time adult kidney transplant (KT) recipients were collected to analyze the "early" (≤30 days) and "late" (31-365 days) HR patterns after KT at a single center over a 12-year time span (2002-2013).

Results: 30-day, 90-day, and 1-year HR were 31%, 41%, and 53%, respectively.

Inverse Association Between the Quantity of Human Peripheral Blood CXCR5+IFN-γ+CD8+ T Cells With De Novo DSA Production in the First Year After Kidney Transplant.

Background: We recently reported that a novel CXCR5IFN-γCD8 T-cell subset significantly inhibits posttransplant alloantibody production in a murine transplant model. These findings prompted the current study to investigate the association of human CD8 T cells with the same phenotype with the development of de novo donor-specific antibody (DSA) after kidney transplantation.

Methods: In the current studies, we prospectively and serially analyzed peripheral blood CD8 and CD4 T-cell subsets and monitored for the development of de novo DSA in kidney transplant recipients during the first-year posttransplant.

Clinical utility of C3d binding donor-specific anti-human leukocyte antigen antibody detection by single antigen beads after kidney transplantation-a retrospective study.

Development of donor-specific antibodies (DSA) after renal transplantation is known to be associated with worse graft survival, yet determining which specificities in which recipients are the most deleterious remains under investigation. This study evaluated the relationship of the complement binding capacity of post-transplant de novo anti-human leukocyte antigen (HLA) antibodies with subsequent clinical outcome. Stored sera from 265 recipients previously identified as having de novo DSA were retested for DSA and their C3d binding capacity using Luminex-based solid-phase assays.

Hospital readmissions following HLA-incompatible live donor kidney transplantation: A multi-center study.

Thirty percent of kidney transplant recipients are readmitted in the first month posttransplantation. Those with donor-specific antibody requiring desensitization and incompatible live donor kidney transplantation (ILDKT) constitute a unique subpopulation that might be at higher readmission risk. Drawing on a 22-center cohort, 379 ILDKTs with Medicare primary insurance were matched to compatible transplant-matched controls and to waitlist-only matched controls on panel reactive antibody, age, blood group, renal replacement time, prior kidney transplantation, race, gender, diabetes, and transplant date/waitlisting date.

Differential gene expression pattern in biopsies with renal allograft pyelonephritis and allograft rejection.

Differentiating acute pyelonephritis (APN) from acute rejection (AR) in renal allograft biopsies can sometimes be difficult because of overlapping clinical and histologic features, lack of positive urine cultures,and variable response to antibiotics. We wanted to study differential gene expression between AR and APN using biopsy tissue. Thirty-three biopsies were analyzed using NanoString multiplex platform and PCR (6 transplant baseline biopsies, 8 AR, 15 APN [8 culture positive, 7 culture negative], and 4 native pyelonephritis [NP]).

High mortality in diabetic recipients of high KDPI deceased donor kidneys.

Background: Deceased donor (DD) kidney quality is determined by calculating the Kidney Donor Profile Index (KDPI). Optimizing high KDPI (≥85%) DD transplant outcome is challenging. This retrospective study was performed to review our high KDPI DD transplant results to identify clinical practices that can improve future outcomes.

Survival Benefit with Kidney Transplants from HLA-Incompatible Live Donors.

Background: A report from a high-volume single center indicated a survival benefit of receiving a kidney transplant from an HLA-incompatible live donor as compared with remaining on the waiting list, whether or not a kidney from a deceased donor was received. The generalizability of that finding is unclear.

Methods: In a 22-center study, we estimated the survival benefit for 1025 recipients of kidney transplants from HLA-incompatible live donors who were matched with controls who remained on the waiting list or received a transplant from a deceased donor (waiting-list-or-transplant control group) and controls who remained on the waiting list but did not receive a transplant (waiting-list-only control group).

Early immunosuppression treatment correlates with later de novo donor-specific antibody development after kidney and pancreas transplantation.

Background: De novo donor-specific antibodies (dnDSA) post-transplant correlate with a higher risk of immunologic graft injury and loss following kidney and pancreas transplantation. Post-transplant dnDSA can occur within the first post-transplant year.

Methods: In this study, 817 of 1290 kidney and simultaneous kidney/pancreas recipients were tested for dnDSA post-transplant.

The safety of hand-assisted laparoscopic living donor nephrectomy: the Ohio State University experience with 1500 cases.

Hand-assisted laparoscopic donor (HALD) nephrectomy has been performed at our institution since December 1999. Through May 2014, a total of 1500 HALD procedures have been performed. We have evaluated the outcomes of HALD.

Human leukocyte antigen type and posttransplant lymphoproliferative disorder.

Background: Posttransplant lymphoproliferative disorder (PTLD) is an infrequent but serious complication of solid organ transplantation. Early detection and initiation of therapy may improve outcomes. The purpose of this study was to identify human leukocyte antigen (HLA) type as risk and prognostic factors for PTLD.

Early posttransplant changes in circulating endothelial microparticles in patients with kidney transplantation.

Background: Endothelial microparticles (EMPs) are membrane vesicles shed from endothelial cell in response to injury, activation or apoptosis. Kidney transplantation (KTx) is the treatment of choice for patients with end stage kidney disease (ESKD). The aim of this study was to analyze changes in EMP and serum creatinine (SCr) in patients following KTx.

Y-chromosome status identification suggests a recipient origin of posttransplant non-small cell lung carcinomas: chromogenic in situ hybridization analysis.

Owing to the need of lifelong immunosuppression, solid-organ transplant recipients are known to have an increased risk of posttransplant malignancies including lung cancer. Posttransplant neoplastic transformation of donor-derived cells giving rise to hematopoietic malignancies, Kaposi sarcoma, and basal cell carcinoma in nongraft tissues has been reported. The goal of this study was to assess the cell origin (donor versus recipient derived) of posttransplant non-small cell lung carcinomas (NSCLCs) in kidney and heart transplant recipients.

Effects of cardiovascular comorbidity adjustment on SRTR risk-adjusted cox proportional hazard models of graft survival.

Background: The Scientific Registry of Transplant Recipients (SRTR) and the Centers for Medicare and Medicaid Services (CMS) determine expected graft survivals to identify potentially underperforming transplant centers. There has been recent interest in evaluating adjustments for comorbidities when performing these calculations. This study was performed to determine the influence that adjustment for pre-transplant cardiovascular disease comorbidity can have on risk-adjusted Cox models, such as those used by SRTR and CMS.

Acute pyelonephritis in renal allografts: a new role for microRNAs?

Background: Acute pyelonephritis (APN) versus acute rejection (AR) is a frequently encountered diagnostic and therapeutic dilemma in kidney transplants. Variable culture results, overlapping histologic features, and persistent graft dysfunction despite antibiotics are frequently encountered. Therefore, we explored the utility of intragraft microRNA profiles to distinguish between allograft APN and AR.

Cardiac stress test as a risk-stratification tool for posttransplant cardiac outcomes in diabetic kidney transplant recipients.

Background: The utility of cardiac stress testing as a risk-stratification tool before kidney transplantation remains debatable owing to discordance with coronary angiography and outcome yields at different centers.

Methods: We conducted a retrospective study of 273 diabetic kidney transplant recipients from 2006 to 2010. By protocol, all diabetic patients underwent pharmacological radionucleotide stress test or dobutamine stress echocardiography before transplant.

Histological spectrum of pulmonary manifestations in kidney transplant recipients on sirolimus inclusive immunosuppressive regimens.

Background: After the introduction of novel effective immunosuppressive therapies, kidney transplantation became the treatment of choice for end stage renal disease. While these new therapies lead to better graft survival, they can also cause a variety of complications. Only small series or case reports describe pulmonary pathology in renal allograft recipients on mTOR inhibitor inclusive therapies.

Histopathology and outcome of acute humoral rejection in renal allografts.

Our purpose was to see if histopathologic features of acute antibody-mediated rejection (AMR) in renal allografts have prognostic value; and to compare two-year graft survival with and without additional therapy with plasmapheresis and intravenous immunoglobulin (IVIG). We reviewed renal allograft biopsies taken within the first 6 months after transplant from patients with C4d positive AMR, performed between January 2000 to December 2005 (n=57). We formed two groups: Group 1: biopsied between 2003 and 2005 (n=26), when C4d staining was routinely performed and option for plasmapheresis and IVIG was available; Group 2: biopsied between 2000 and 2002 (n=31), retrospectively found to be C4d positive.

Twenty-five year evolution of kidney transplantation at the Ohio State University.

Over the course of the last 25 years, we have seen dramatic improvements in the outcomes following kidney transplantation at The Ohio State University. With the employment of each new pharmacologic or biologic agent, came a reduction in the incidence of acute rejection within the first post-transplant year and beyond as reported in these analyses. This dramatic reduction in acute rejection over progressive eras translated into significantly improved graft survivals.

Change in bone mineral density at one year following glucocorticoid withdrawal in kidney transplant recipients.

Glucocorticoid (GC) therapy induces deleterious effects on the skeleton in kidney transplantation but studies of GC discontinuation in this population are limited. This study evaluated changes in areal bone mineral density (BMD) with GC withdrawal. Subjects were enrolled one yr after renal transplantation and randomized to continue or stop prednisone; all subjects continued cyclosporine and mycophenolate mofetil.

Expression of the decay-accelerating factor (CD55) in renal transplants--a possible prediction marker of allograft survival.

Background: Decay-accelerating factor (CD55) accelerates the decay of C3 and C5 convertases, participating in classical and alternative complement activation pathways. Complement activation plays a major role in antibody-mediated rejection of allografts (AMR); C4d is used as a marker of AMR. Emerging evidence suggests an important role of CD55 in the pathogenesis of AMR.

Multicenter evaluation of a novel endothelial cell crossmatch test in kidney transplantation.

Background: Despite their clinical importance, clinical routine tests to detect anti-endothelial cell antibodies (AECA) in organ transplantation have not been readily available. This multicenter prospective kidney transplantation trial evaluates the efficacy of a novel endothelial cell crossmatch (ECXM) test to detect donor-reactive AECA associated with kidney allograft rejection.

Methods: Pretransplant serum samples from 147 patients were tested for AECA by a novel flow cytometric crossmatch technique (XM-ONE) using peripheral blood endothelial progenitor cells as targets.