Renal Arteriosclerosis in kidney biopsies associated with higher 10-year atherosclerotic cardiovascular disease in lupus nephritis.

Objective: Patients with lupus nephritis (LN), including those below age 50, face significantly higher risk of atherosclerotic cardiovascular disease (ASCVD) vs. peers. This highlights the need for identifying specific ASCVD risk factors in LN.

Multidisciplinary Lupus Nephritis Clinic Reduces Time to Renal Biopsy and Improves Care Quality.

Objective: Patients with lupus nephritis (LN) have a 26-fold higher mortality rate compared with their peers. Kidney biopsy, the gold standard diagnostic method for LN, may have an average wait time of more than 50 days. Other gaps in quality process measures during LN visits have also been reported.

Natural antibody and complement activation characterize patients with idiopathic nephrotic syndrome.

Focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) are common forms of idiopathic nephrotic syndrome. The causes of these diseases are incompletely understood, but the response of patients to immunosuppressive therapies suggests that their pathogenesis is at least in part immune mediated. Preclinical and clinical research indicates that activation of the classical pathway of complement contributes to glomerular injury in FSGS.

Macrophages in Transplantation: A Matter of Plasticity, Polarization, and Diversity.

Macrophages have emerged at the forefront of research in immunology and transplantation because of recent advances in basic science. New findings have illuminated macrophage populations not identified previously, expanded upon traditional macrophage phenotypes, and overhauled macrophage ontogeny. These advances have major implications for the field of transplant immunology.

Association of Renal Arteriosclerosis With Atherosclerotic Cardiovascular Disease Risk in Lupus Nephritis.

Objective: Lupus nephritis (LN) predicts a 9-fold higher atherosclerosis cardiovascular disease (ASCVD) risk, highlighting the urgent need to target ASCVD prevention. Studies in IgA nephropathy reported that severe renal arteriosclerosis (r-ASCL) in diagnostic biopsies strongly predicted ASCVD risk. We recently found that 50% of LN pathology reports overlooked r-ASCL reporting, which could explain prior negative LN ASCVD risk studies.

B-cell Deficiency Attenuates Transplant Glomerulopathy in a Rat Model of Chronic Active Antibody-mediated Rejection.

Background: Transplant glomerulopathy (TG) is a pathological feature of chronic active antibody-mediated rejection (cAMR) and is associated with renal allograft failure. The specific role of B cells in the pathogenesis of TG is unclear.

Methods: We used a minor mismatched rat kidney transplant model with B cell-deficient recipients, generated by clustered regularly interspaced short palindromic repeats/Cas9 technology, to investigate the impact of B-cell depletion on the pathogenesis of TG.

Long-term outcomes in kidney transplant recipients with end-stage kidney disease due to anti-glomerular basement membrane disease.

Anti-glomerular basement membrane (GBM) disease causes rapidly progressive glomerulonephritis and end-stage kidney disease (ESKD). Studies of post-transplant outcomes in patients with ESKD due to anti-GBM disease in the United States are lacking. To better characterize outcomes of transplant recipients with a history of anti-GBM disease, we examined patient survival and graft survival among recipients with anti-GBM disease compared with IgA nephropathy at a single center in the United States.

Isolation, purification, and conditional immortalization of murine glomerular endothelial cells of microvascular phenotype.

Glomerular endothelial cells (GEnC) are a specialized microvascular subset of endothelial cells that, when injured, result in many types of diseases within the kidney. Thus, techniques to study GEnC in a cell culture system are important to investigate mechanisms of GEnC injury. Studies of endothelial cell function in culture have predominately relied on using macrovascular endothelial cells from vascular areas other than the glomerulus.

Short-term Immunopathological Changes Associated with Pulse Steroids/IVIG/Rituximab Therapy in Late Kidney Allograft Antibody Mediated Rejection.

Background: B-cell depletion is a common treatment of antibody-mediated rejection (ABMR). We sought to determine the specific immunopathologic effects of this therapeutic approach in kidney transplantation.

Methods: This was a prospective observational study of kidney transplant recipients diagnosed with late ABMR (>3 months after transplant).

Oxidized-ATP Attenuates Kidney Allograft Rejection By Inhibiting T-Cell, B-Cell, and Macrophage Activity.

Background: Extracellular ATP binds to purinergic receptors and promotes inflammatory responses. We tested whether oxidized ATP (oATP), P2X7 receptor antagonist can attenuate acute kidney allograft rejection.

Methods: Brown Norway kidney allografts were transplanted into Lewis recipients.

High Burden of Premature Arteriosclerosis on Renal Biopsy Results in Incident Lupus Nephritis.

Objective: Cardiovascular disease (CVD) is accelerated in patients with systemic lupus erythematosus and lupus nephritis (LN). Despite the literature suggesting that renal arteriosclerosis predicts CVD in other glomerulonephritis diseases, arteriosclerosis grading and reporting might be particularly overlooked in LN biopsies. Our objective was to examine the burden of renal arteriosclerosis in LN and to assess whether arteriosclerosis is underreported in LN biopsies.

An in vitro model of antibody-mediated injury to glomerular endothelial cells: Upregulation of MHC class II and adhesion molecules.

Chronic active antibody-mediated rejection is a major cause of allograft failure in kidney transplantation. Microvascular inflammation and transplant glomerulopathy are defining pathologic features of chronic active antibody-mediated rejection and are associated with allograft failure. However, the mechanisms of leukocyte infiltration and glomerular endothelial cell injury remain unclear.

Histopathological characteristics and causes of kidney graft failure in the current era of immunosuppression.

Background: The histopathological findings on the failing kidney allograft in the modern era is not well studied. In this study, we present our experience working with kidney transplant recipients with graft failure within one year of the biopsy.

Aim: To report the histopathological characteristics of failed kidney allografts in the current era of immunosuppression based on the time after transplant, cause of the end-stage renal disease and induction immunosuppressive medications.

The association of acute rejection vs recurrent glomerular disease with graft outcomes after kidney transplantation.

Background: It has been shown that glomerulonephritis (GN) recurrence affects graft survival more than acute rejection. Thus, we assessed allograft survival after biopsy-confirmed diagnosis of acute rejection or recurrent GN in current era of immunosuppression.

Methods: Allograft survival following a biopsy diagnosis of acute rejection or recurrent GN was determined in adult kidney transplant recipients from 1994 to 2013.

Cause of End-Stage Renal Disease Is Not a Risk Factor for Cytomegalovirus Infection After Kidney Transplant.

Background: Cytomegalovirus infection (CMV) after kidney transplantation leads to increased morbidity and mortality. Whether the cause of end-stage renal disease (ESRD) influences the risk of CMV infection post-transplant is not known.

Methods: We analyzed data from 2741 adult kidney transplant recipients from January 1993 through December 2014.

The role of complement in antibody mediated transplant rejection.

Antibody mediated transplant rejection (AMR) is a major cause of long-term allograft failure, and currently available treatments are of limited efficacy for treating the disease. AMR is caused by donor specific antibodies (DSA) that bind to antigens within the transplanted organ. DSA usually activate the classical pathway of complement within the allograft, and complement activation is believed to be an important cause of tissue injury in AMR.

Glomerular C3 Deposition Is an Independent Risk Factor for Allograft Failure in Kidney Transplant Recipients With Transplant Glomerulopathy.

Introduction: Transplant glomerulopathy (TG) becomes increasingly prevalent in kidney transplant recipients over time, and it is strongly associated with allograft failure. To date, our prognostic biomarkers and understanding of the processes of immunologic injury in TG are limited.

Methods: This is a retrospective cohort analysis of kidney transplant recipients with TG (double contours of the glomerular basement membrane as defined by the chronic glomerulopathy score).

APRIL/BLyS Blockade Reduces Donor-specific Antibodies in Allosensitized Mice.

Background: Highly sensitized candidates on the transplant waitlist remain a significant challenge, as current desensitization protocols have variable success rates of donor-specific antibody (DSA) reduction. Therefore, improved therapies are needed. A proliferation-inducing ligand (APRIL) and B-lymphocyte stimulator (BLyS) are critical survival factors for B-lymphocytes and plasma cells, which are the primary sources of alloantibody production.

Directed Differentiation of Human Pluripotent Stem Cells to Podocytes under Defined Conditions.

A major cause of chronic kidney disease (CKD) is glomerular disease, which can be attributed to a spectrum of podocyte disorders. Podocytes are non-proliferative, terminally differentiated cells. Thus, the limited supply of primary podocytes impedes CKD research.

Desensitization and treatment with APRIL/BLyS blockade in rodent kidney transplant model.

Alloantibody represents a significant barrier in kidney transplant through the sensitization of patients prior to transplant through antibody mediated rejection (ABMR). APRIL BLyS are critical survival factors for mature B lymphocytes plasma cells, the primary source of alloantibody. We examined the effect of APRIL/BLyS blockade via TACI-Ig (Transmembrane activator calcium modulator cyclophilin lig interactor-Immunoglobulin) in a preclinical rodent model as treatment for both desensitization ABMR.

Autologous Mesenchymal Stromal Cells Prevent Transfusion-elicited Sensitization and Upregulate Transitional and Regulatory B Cells.

Background: We hypothesized that immunomodulatory properties of mesenchymal stromal cells (MSC) may be considered for desensitization.

Methods: Autologous or allogeneic bone marrow derived MSC were infused tail vein at 0.5 M (0.

Kidney transplant recipients with polycystic kidney disease have a lower risk of post-transplant BK infection than those with end-stage renal disease due to other causes.

Background: Polyomavirus-associated nephropathy is associated with high risk of kidney allograft loss. Whether the cause of native end-stage renal disease influences the risk of BK infection is unclear.

Methods: A retrospective, single-center study of 2741 adult kidney transplant recipients between 1994 and 2014 was performed.