HLA class, calcineurin inhibitor levels, and the risk of graft failure in kidney recipients with donor-specific antibodies.

Introduction: De novo donor-specific HLA antibody (dnDSA) are associated with poor outcomes. Whether this observation applies to both HLA class I and II dnDSA remains unclear.

Methods: We studied 1236 consecutive kidney recipients who had routine anti-HLA antibody surveillance post-transplant.

Factors Associated With the Use of Hypothermic Machine Perfusion in Kidney Transplant Recipients: A Multicenter Retrospective Cohort Study.

Background: Delayed graft function (DGF) is associated with an increased risk of graft loss. The use of cold hypothermic machine perfusion (HMP) has been shown to reduce the incidence of DGF in kidney transplant recipients (KTRs), especially when extended-criteria donors (ECDs) are used. HMP can also improve graft survival.

Immunosuppressant Medication Use in Patients with Kidney Allograft Failure: A Prospective Multicenter Canadian Cohort Study.

Background: Patients with kidney transplant failure have a high risk of hospitalization and death due to infection. The optimal use of immunosuppressants after transplant failure remains uncertain and clinical practice varies widely.

Methods: This prospective cohort study enrolled patients within 21 days of starting dialysis after transplant failure in 16 Canadian centers.

A Sequential Two-Step Cell-Based Assay Predicts Immunosuppression-Related Adverse Events.

Immunosuppressants are associated with serious and often life-threatening adverse effects. To optimize immunotherapy, a tool that measures the immune reserve is necessary. We validated that a cell-based assay that measures TNF-α production by CD1416 intermediate monocytes following stimulation with EBV peptides has high sensitivity for the detection of over-immunosuppression (OIS) events.

Canadian Society of Transplantation and Canadian Society of Nephrology Commentary on the 2017 KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors.

Purpose Of Review: To review an international guideline on the evaluation and care of living kidney donors and provide a commentary on the applicability of the recommendations to the Canadian donor population.

Sources Of Information: We reviewed the 2017 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors and compared this guideline to the Canadian 2014 Kidney Paired Donation (KPD) Protocol for Participating Donors.

Methods: A working group was formed consisting of members from the Canadian Society of Transplantation and the Canadian Society of Nephrology.

TNF-α Production by Monocytes Stimulated With Epstein-Barr Virus-Peptides as a Marker of Immunosuppression-Related Adverse Events in Kidney Transplant Recipients.

Introduction: Infections and cancers now outnumber rejection as a cause of morbidity in transplant recipients, likely as a result of over-immunosuppression. Currently, there is no clinical tool to detect over-immunosuppression. We recently reported that tumor necrosis factor alpha (TNF-α) production by CD14CD16 intermediate monocytes, following stimulation by Epstein-Barr virus-peptides, could identify over-immunosuppressed patients.

Comparison of the effects of standard vs low-dose prolonged-release tacrolimus with or without ACEi/ARB on the histology and function of renal allografts.

Targeting the renin-angiotensin system and optimizing tacrolimus exposure are both postulated to improve outcomes in renal transplant recipients (RTRs) by preventing interstitial fibrosis/tubular atrophy (IF/TA). In this multicenter, prospective, open-label controlled trial, adult de novo RTRs were randomized in a 2 × 2 design to low- vs standard-dose (LOW vs STD) prolonged-release tacrolimus and to angiotensin-converting enzyme inhibitors/angiotensin II receptor 1 blockers (ACEi/ARBs) vs other antihypertensive therapy (OAHT). There were 2 coprimary endpoints: the prevalence of IF/TA at month 6 and at month 24.

Organ donor management and delayed graft function in kidney transplant recipients: A multicenter retrospective cohort study.

Meeting donor management goals (DMGs) has been reported to decrease the incidence of delayed graft function (DGF) after kidney transplant, but whether this relationship is independent of cold machine perfusion is unclear. We aimed to determine whether meeting DMGs is associated with a reduced incidence of DGF, independent of the use of machine perfusion. We collected data on consecutive brain-dead donors and their KT recipients (KTRs) between June 2013 and December 2016 in 5 adult transplant centers.

Impact of the Current Versus the Previous Diagnostic Threshold on the Outcome of Patients With Borderline Changes Suspicious for T Cell-mediated Rejection Diagnosed on Indication Biopsies.

Background: Since the borderline changes suspicious for acute T cell-mediated rejection (BL) category was broadened, there has been a debate regarding the right threshold for tubulitis and interstitial inflammation scores.

Methods: We studied a first cohort of 111 patients with BL found on an indication biopsy between 2006 and 2016 and compared those with scores of t1i0 (BLt1i0) to those with higher scores (BL≥t1i1). A second cohort of 56 patients with BL was used for external validation.

Impaired Secretion of TNF-α by Monocytes Stimulated With EBV Peptides Associates With Infectious Complications After Kidney Transplantation.

Background: The successful development of immunosuppressive agents has paradoxically led to an era in which adverse effects of immunosuppression, such as infections and cancer, are now a major concern in solid organ recipients. Nevertheless, the main focus of immune monitoring research remains the identification of rejection. There is currently no clinical tool to assess the net state of immunosuppression or to identify patients at increased risk of infectious complications.

Donor-specific antibodies, C4d and their relationship with the prognosis of transplant glomerulopathy.

Background: Transplant glomerulopathy (TG) is a diagnostic criterion for chronic active antibody-mediated rejection (CAABMR), with C4d, donor-specific antibodies (DSA) and other lesions of chronic tissue injury. However, TG often presents without C4d or DSA. Until recently, such cases were termed suspicious for CAABMR, and their prognosis remains unclear.

Impact of donor age on long-term outcomes after delayed graft function: 10-year follow-up.

Delayed graft function (DGF) has a negative impact on graft survival in donation after brain death (DBD) but not for donation after cardiac death (DCD) kidneys. However, older donor age is associated with graft loss in DCD transplants. We sought to examine the interaction between donor age and DGF in DBD kidneys.

Dual-kidney transplants as an alternative for very marginal donors: long-term follow-up in 63 patients.

Background: Organ shortage has led to the use of dual-kidney transplant (DKT) of very marginal donors into a single recipient to increase the use of marginal organs. To date, few data are available about the long-term outcome of DKT and its usefulness to increase the pool of available organ.

Methods: We conducted a single-center cohort study of DKTs with longitudinal follow-up over an 8-year period.

Age-related and blood pressure-independent reduction in aortic stiffness after kidney transplantation.

Objectives: Aortic stiffness is a novel cardiovascular risk factor in patients with chronic kidney disease (CKD). The purpose of the present study is to examine whether there is a blood pressure-independent improvement in aortic stiffness 3 months after successful kidney transplantation (KTx), and whether this improvement is age-dependent.

Method: In this prospective, longitudinal observational study, we studied hemodynamic and biological parameters prior to and 3 months after a KTx in 52 stage 5 CKD patients.

The CLEAR study: a 5-day, 3-g loading dose of mycophenolate mofetil versus standard 2-g dosing in renal transplantation.

Background And Objectives: Adequate early mycophenolic acid (MPA) exposure is associated with lower rates of acute rejection in renal transplantation. The aim of this randomized controlled trial was to determine if higher initial mycophenolate mofetil (MMF) doses increased the proportion of patients reaching therapeutic MPA levels (30 to 60 mg.h/L) by day 5.

Screening for polyomavirus associated nephropathy in renal transplantation with blood viral load measurement.

Background: Polyomavirus associated nephropathy (PVAN) is an important cause of graft failure in the renal transplant population. It has been shown that viremia precedes PVAN, suggesting that measurement of blood viral load could be used for PVAN screening.

Objectives: To verify the utility of BK virus (BKV) blood viral load measurement for PVAN screening in the renal transplant population, establish a threshold value, and determine the sensitivity and specificity of the test.

Modifiable factors predicting patient survival in elderly kidney transplant recipients.

Background: Elderly transplant candidates represent an increasingly important group on the waiting list for kidney transplantation. Yet the factors that determine posttransplantation outcomes in this population remain poorly defined.

Methods: We performed a population-based retrospective cohort study involving all patients aged 60 years or older who received a first cadaveric kidney transplantation between 1985 and 2000 in the province of Quebec.

Endothelin-1 levels and cardiovascular risk factors in renal transplant patients.

Objective: Circulating endothelin-1 (ET-1) levels have been reported to be associated with vascular complications and endothelial dysfunction in nontransplanted patients. The aim of this study was to investigate the relationship between ET-1 levels and major cardiovascular (CV) risk factors in renal transplant (RTX) patients with stable graft function.

Methods: ET-1 levels were determined in 156 RTX patients and the relationship between circulating ET-1 levels and CV risk factors including age, gender, kidney function, blood lipids, diabetes, and hypertension was studied.

Effects of prednisone withdrawal on the new metabolic triad in cyclosporine-treated kidney transplant patients.

Background: Cardiovascular disease is a major cause of morbidity and mortality after renal transplantation. Prednisone (Pred) maintenance therapy is associated with risk factors for atherosclerosis. Therefore, we were interested in quantifying the effects of Pred withdrawal on body weight and waist circumference as well as on metabolic markers of coronary heart disease risk.