Improved ability to achieve target trough levels with liquid versus capsule tacrolimus in kidney transplant patients with HIV on protease inhibitor- or cobicistat-based regimens.

HIV + patients are commonly accepted for kidney transplantation. However, patients on protease inhibitor (PI)- or cobicistat (cobi)-based regimens have trouble achieving optimal tacrolimus (Tac) levels. Our study compared the ability to achieve target levels using liquid versus immediate-release capsule Tac in kidney transplant patients with HIV on PI- or cobi-based regimens.

A pilot study of immunosuppression resumption following BK viremia resolution.

Background: Immunosuppression reduction for BK viremia is associated with de novo humoral responses, which are a risk factor for rejection and graft loss. In this pilot project, we tested a protocol of immunosuppression resumption to standard dose after viral clearance for optimal protection against humoral immunity in patients undergoing treatment for BK viremia.

Methods: Thirty-six consecutive kidney transplant recipients who developed BK viremia from 7/1/2014 to 11/18/2016 underwent immunosuppression reduction.

Outcomes of induction antibody therapies in the nonbroadly sensitized adult deceased donor kidney transplant recipients: a retrospective cohort registry analysis.

The outcomes of lymphocyte-depleting antibody induction therapy (LDAIT), [thymoglobulin (ATG) or alemtuzumab (ALM)] versus interleukin-2 receptor antagonist (IL-2RA) in the nonbroadly-sensitized [pretransplant calculated panel reactive antibody (cPRA), <80%] adult deceased donor kidney transplant recipients (adult-DDKTRs) are understudied. In this registry, study of 55 593 adult-DD-KTRs, outcomes of LDAIT [(ATG, N = 32 985) and (ALM, N = 9429)], and IL-2RA (N = 13 179) in <10% and 10-79% cPRA groups was analyzed. Adjusted odds ratio (aOR) of one-year biopsy-proven acute rejection (BPAR) was lower; while, aOR of 1-year composite of re-hospitalization, graft loss, or death was higher with LDAIT than IL2-RA in both cPRA groups.

Not all inflammation in a renal allograft is rejection.

High index of suspicion for adenovirus infection is required in renal graft dysfunction, especially in the setting of hematuria. Histology can mimic acute rejection, which creates a diagnostic dilemma. Tissue adenovirus immunostains, though usually reliable, may not be always positive like in our case.

Analysis of Risk Factors for Kidney Retransplant Outcomes Associated with Common Induction Regimens: A Study of over Twelve-Thousand Cases in the United States.

We studied registry data of 12,944 adult kidney retransplant recipients categorized by induction regimen received into antithymocyte globulin (ATG) ( = 9120), alemtuzumab ( = 1687), and basiliximab ( = 2137) cohorts. We analyzed risk factors for 1-year acute rejection (AR) and 5-year death-censored graft loss (DCGL) and patient death. Compared with the reference, basiliximab: (1) one-year AR risk was lower with ATG in retransplant recipients of expanded criteria deceased-donor kidneys (HR = 0.

New-onset diabetes after kidney transplantation: can the risk be modified by choosing immunosuppression regimen based on pretransplant viral serology?

Background: This study aimed to analyze adult kidney transplant recipients (KTRs) for the risk of new-onset diabetes after transplantation (NODAT) associated with viral serologies and immunosuppression regimens [tacrolimus (Tac) + mycophenolate (MPA), cyclosporine (CSA) + MPA, sirolimus (SRL) + MPA, SRL + CSA or SRL +Tac].

Methods: Cox regression models were used to examine the risk of NODAT in the first posttransplant year associated with: (i) CSA + MPA, SRL + MPA, SRL + MPA or SRL + Tac versus reference, Tac + MPA; (ii) pretransplant viral serology [+ or -; hepatitis B core (HBc), hepatitis C (HCV), cytomegalovirus (CMV) or Epstein Barr Virus (EBV)]; and (iii) interactions between immunosuppression regimens and the viral serology found significant in the main analysis.

Results: Adult KTRs (n = 97 644) from January 1995 through September 2015 were studied.

Association of Baseline Viral Serology and Sirolimus Regimens With Kidney Transplant Outcomes: A 14-Year Registry-Based Cohort Study in the United States.

Background: The risks for transplant outcomes associated with baseline viral serostatus in kidney transplant recipients (KTR) on sirolimus have not been widely studied.

Methods: We performed a cohort-study of 61 590 adult KTR in 2000 to 2013. We used Cox regression models to determine the adjusted hazard ratio (aHR) of patient death, death-censored graft loss and posttransplant malignancy associated with the baseline serostatus (+ or -: hepatitis B core [HBc], hepatitis C virus [HCV], Epstein-Barr virus [EBV], or cytomegalovirus [CMV]) in KTR on sirolimus (SRL) + mycophenolate (MPA) or SRL + tacrolimus (Tac), relative to the control-regimen: Tac + MPA.

Comparison of Utilization and Clinical Outcomes for Belatacept- and Tacrolimus-Based Immunosuppression in Renal Transplant Recipients.

The performance of belatacept in a real clinical setting has not been reported. A retrospective cohort study was conducted using registry data comparing 1-year clinical outcomes between belatacept- and tacrolimus-treated adult kidney transplant recipients (KTRs) from January 6, 2011, through January 12, 2014. Of 50 244 total patients, 417 received belatacept plus tacrolimus, 458 received belatacept alone, and 49 369 received tacrolimus alone at discharge.

Effects of mesenchymal stromal cells on human myeloid dendritic cell differentiation and maturation in a humanized mouse model.

Mesenchymal stromal cells (MSCs) have shown promise as cellular therapy in allogeneic transplantation, although the precise mechanisms underlying their benefit in clinical trials are difficult to study. We previously demonstrated that MSCs exert immunoregulatory effects in mouse bone marrow-derived dendritic cell (DC) culture. Since mouse studies do not reliably reproduce human events, we used a humanized mouse model to study the immunomodulatory effects of human MSCs on human DC immunobiology.

Survival With Dialysis Versus Kidney Transplantation in Adult Hemolytic Uremic Syndrome Patients: A Fifteen-Year Study of the Waiting List.

Background: Survival data are lacking for kidney transplant recipients with rare native end-stage renal disease (ESRD) etiologies. There is currently no large registry study comparing dialysis versus kidney transplantation survival outcomes of waitlisted adults with hemolytic uremic syndrome (HUS).

Materials And Methods: We retrospectively studied adult-HUS end-stage renal disease patients (n = 559) placed on the US kidney transplant waitlist in 1996 to 2011.

Blood dendritic cell levels associated with impaired IL-12 production and T-cell deficiency in patients with kidney disease: implications for post-transplant viral infections.

Reduced pretransplant blood myeloid dendritic cell (mDC) levels are associated with post-transplant BK viremia and cytomegalovirus (CMV) disease after kidney transplantation. To elucidate potential mechanisms by which mDC levels might influence these outcomes, we studied the association of mDC levels with mDC IL-12 production and T-cell level/function. Peripheral blood (PB) was studied in three groups: (i) end stage renal disease patients on hemodialysis (HD; n = 81); (ii) chronic kidney disease stage IV-V patients presenting for kidney transplant evaluation or the day of transplantation (Eval/Tx; n = 323); and (iii) healthy controls (HC; n = 22).

Pre-transplant myeloid dendritic cell deficiency associated with cytomegalovirus infection and death after kidney transplantation.

Background: Dendritic cells (DCs) are potent antigen-presenting cells critical for immunity. We previously demonstrated a significant association between pre-transplant blood myeloid dendritic cell (mDC) and plasmacytoid dendritic cell (pDC) deficiency and post-transplant BK viremia in renal transplant recipients. In the current post-hoc analysis, we studied the association of these same pre-transplant DC levels with other post-transplant outcomes.

Incidence and outcomes of BK virus allograft nephropathy among ABO- and HLA-incompatible kidney transplant recipients.

Background And Objectives: ABO-incompatible kidney transplant recipients may have a higher incidence of BK virus allograft nephropathy (BKVAN) compared with ABO-compatible recipients. It is unclear whether HLA-incompatible recipients share this risk or whether this phenomenon is unique to ABO-incompatible recipients. DESIGN, SETTING, PARTICIPATION, MEASUREMENTS: This study analyzed adult incompatible kidney transplant recipients from 1998 to 2010 (62 ABO-incompatible and 221 HLA-incompatible) and identified patients in whom BKVAN was diagnosed by biopsy (per protocol or for cause).

Inhibition of Fas ligand in NOD mice unmasks a protective role for IL-10 against insulitis development.

Type 1 diabetes mellitus (T1D) is an autoimmune disease caused by the destruction of pancreatic insulin-producing β cells by autoreactive T cells early in life. Despite daily insulin injections, patients typically develop cardiovascular and other complications; and intensive efforts are being directed toward identifying therapeutic targets to prevent the disease without directly impinging on the host defense. Fas ligand (FasL) is one potential target.

Blocking Fas ligand on leukocytes attenuates kidney ischemia-reperfusion injury.

Inflammation contributes to the pathogenesis of ischemic acute kidney injury (AKI), and T cells mediate the early phase of ischemia-reperfusion injury (IRI). The Fas/Fas ligand (FasL) pathway modulates the balance of T cell subsets in the peripheral circulation as well as multiple inflammatory responses, suggesting that FasL may mediate ischemic AKI. Here, we induced bilateral renal IRI in mice bearing a loss-of-function mutation of FasL (the gld mutation) and in wild-type mice.

Profile of belatacept and its potential role in prevention of graft rejection following renal transplantation.

The last several decades have witnessed a substantial decrease in the incidence of acute allograft rejection following kidney transplantation, although commensurate improvements in long-term graft function have not been realized. As a result, the primary focus of new immunosuppressive drug development has expanded to include ease of use and improved side effect profile, including reduced nephrotoxicity, in addition to the more traditional goal of improved short-term outcomes. A number of novel drugs are currently under investigation in Phase I, II, or III clinical trials, primarily to replace the nephrotoxic but highly effective calcineurin inhibitors.

Stem cell factor, interleukin-16, and interleukin-2 receptor alpha are predictive biomarkers for delayed and slow graft function.

Introduction: Delayed graft function (DGF) and slow graft function (SGF) due to ischemic and reperfusion injury (IRI) are common complications of deceased donor kidney transplantation. We tested whether a panel of serum and urine cytokines represent early biomarkers for DGF and SGF.

Methods: We collected serum and urine samples from 61 patients 48 hours posttransplantation and used a multiplex enzyme-linked immunosorbent assay (ELISA) technique to measure levels of 23 cytokines.

Kidney-derived mesenchymal stromal cells modulate dendritic cell function to suppress alloimmune responses and delay allograft rejection.

Background: Mesenchymal stromal cells (MSCs) are multipotent cells with immunoregulatory capacity that are present in most adult organs. We previously demonstrated that co-culture of C57BL/6 kidney-derived MSCs (KSCs) in syngeneic bone marrow-derived dendritic cell (DC) culture induced a DC phenotype (KSC-DC) with reduced major histocompatibility complex (MHC) class II/increased CD80 expression and ability to suppress T-cell responses.

Methods: To study their effects on allogeneic DCs, C57BL/6 KSCs were added to incipient BALB/c DC culture, with surface expression of MHC class II/CD80 measured by fluorescence-activated cell sorting.

Laparoscopic live donor nephrectomy with vaginal extraction: initial report.

The recent decrease in the total number of living kidney transplants coupled with the increase in the number of candidates on the waiting list underscores the importance of eliminating barriers to living kidney donation. We report what we believe to be the first pure right-sided laparoscopic live donor nephrectomy with extraction of the kidney through the vagina. The warm ischemia time was 3 min and the renal vessels and ureter of the procured kidney were of adequate length for routine transplantation.

Listing for expanded criteria donor kidneys in older adults and those with predicted benefit.

Certain patient groups are predicted to derive significant survival benefit from transplantation with expanded criteria donor (ECD) kidneys. An algorithm published in 2005 by Merion and colleagues characterizes this group: older adults, diabetics and registrants at centers with long waiting times. Our goal was to evaluate ECD listing practice patterns in the United States in terms of these characteristics.

Immunologic research in kidney ischemia/reperfusion injury at Johns Hopkins University.

Kidney ischemia/reperfusion injury (IRI) is a common and serious problem in hospitalized patients. Immune cell trafficking and leukocyte-endothelial adhesion potentiate kidney IRI. An important immunomodulatory role of T lymphocytes has been elucidated in IRI.

Dendritic cell deficiency associated with development of BK viremia and nephropathy in renal transplant recipients.

Background: BK virus nephropathy (BKVN) is a significant cause of renal allograft loss. Although overall intensity of immunosuppression is the greatest risk factor, recipient immune factors likely also play a role in the pathogenesis. Dendritic cells (DC) are potent antigen-presenting cells important for the induction of anti-viral cytotoxic T-cell responses.

Recent developments in kidney transplantation--a critical assessment.

Rapid advances have been made in decreasing acute rejection rates and improving short-term graft survival in kidney transplant recipients. Whether these advances ultimately will lead to a commensurate improvement in long-term survival is not yet known. In recent years, greater attention has been placed on defining the precise etiology of graft loss, determining how far and with what agents we can minimize immunosuppression, and delineating the nature of both T-cell-mediated as well as antibody-mediated rejection.