A paired-kidney allocation study found superior survival with HLA-DR compatible kidney transplants in the Eurotransplant Senior Program.

The Eurotransplant Senior Program (ESP) has expedited the chance for elderly patients with kidney failure to receive a timely transplant. This current study evaluated survival parameters of kidneys donated after brain death with or without matching for HLA-DR antigens. This cohort study evaluated the period within ESP with paired allocation of 675 kidneys from donors 65 years and older to transplant candidates 65 years and older, the first kidney to 341 patients within the Eurotransplant Senior DR-compatible Program and 334 contralateral kidneys without (ESP) HLA-DR antigen matching.

A Combined microRNA and Chemokine Profile in Urine to Identify Rejection After Kidney Transplantation.

Unlabelled: There is an unmet need for noninvasive tools for diagnosis of rejection after kidney transplantation. The aim of this study was to determine the discriminative value of a combined cellular and molecular biomarker platform in urine for the detection of rejection.

Methods: First, microRNA (miR) molecules were screened in transplant biopsies and urine sediments of patients with acute rejection and patients without rejection and stable graft function.

Superior Long-term Survival for Simultaneous Pancreas-Kidney Transplantation as Renal Replacement Therapy: 30-Year Follow-up of a Nationwide Cohort.

Objective: In patients with type 1 diabetes and end-stage renal disease, it is controversial whether a simultaneous pancreas-kidney (SPK) transplantation improves survival compared with kidney transplantation alone. We compared long-term survival in SPK and living- or deceased-donor kidney transplant recipients.

Research Design And Methods: We included all 2,796 patients with type 1 diabetes in the Netherlands who started renal replacement therapy between 1986 and 2016.

Elevated intragraft expression of innate immunity and cell death-related markers is a risk factor for adverse graft outcome.

Background: Molecules of the innate immune response are increasingly recognized as important mediators in allograft injury during and after kidney transplantation. We therefore aimed to establish the relationship between the expression of these genes at implantation, during an acute rejection (AR) and on graft outcome.

Methods: A total of 19 genes, including Toll like receptors (TLRs), complement components and regulators, and apoptosis-related genes were analyzed at the mRNA level by qPCR in 123 biopsies with acute rejection and paired pre-transplantation tissue (n = 75).

Acute Rejection After Kidney Transplantation Associates With Circulating MicroRNAs and Vascular Injury.

Background: Acute rejection (AR) of kidney transplants is associated with the loss of endothelial integrity, microvascular rarefaction and, ultimately, graft dysfunction. Circulating angiogenic microRNAs (miRNAs) may serve as markers for microvascular injury. Here, we investigated the short- and long-term effects of AR after kidney transplantation on systemic vascular injury and the associated circulating miRNA profile.

Alemtuzumab Induction and Delayed Acute Rejection in Steroid-Free Simultaneous Pancreas-Kidney Transplant Recipients.

Background: The optimal immunosuppressive regimen in simultaneous pancreas-kidney transplant (SPKT) recipients that prevents acute rejection episodes (AREs) and allows optimal outcome remains elusive.

Methods: This cohort study assessed incidence and time to AREs in 73 consecutive SPKT recipients receiving alemtuzumab induction and steroid-free maintenance with tacrolimus and mycophenolate mofetil. A cohort with single high-dose antithymocyte globulin (ATG; n = 85) and triple therapy served as controls.

Donor Genotype and Intragraft Expression of CYP3A5 Reflect the Response to Steroid Treatment During Acute Renal Allograft Rejection.

Background: Glucocorticoid (GC)-refractory acute rejection (AR) is a risk factor for inferior renal allograft outcome. We investigated genetic predisposition to the response to steroid treatment of acute allograft rejection.

Methods: Single nucleotide polymorphisms of genes involved in GC signaling (GR, GLCCI1) and drug metabolism and transport (CYP3A5, ABCB1, and PXR) were analyzed in kidney transplant recipients (1995-2005, Leiden cohort, n = 153) treated with methylprednisolone.

Pretransplantation GAD-autoantibody status to guide prophylactic antibody induction therapy in simultaneous pancreas and kidney transplantation.

Background: Daclizumab and antithymocyte globulin (ATG) have been shown to reduce allograft rejection. We assessed the safety and efficacy of daclizumab or ATG prophylaxis in combination with triple immunotherapy in simultaneous pancreas-kidney transplant (SPKT) recipients.

Methods: Thirty-nine type 1 diabetic patients scheduled for primary SPKT were randomized to receive prophylactic therapy with either daclizumab or ATG.

Late calcineurin inhibitor withdrawal prevents progressive left ventricular diastolic dysfunction in renal transplant recipients.

Background: Calcineurin inhibitor (CNI)-based therapy is associated with adverse cardiovascular effects. We examined the effects of late CNI or mycophenolate mofetil (MMF) withdrawal on echocardiographic parameters.

Methods: This study was conducted as a substudy of a randomized trial in stable renal transplant recipients who were on a triple CNI-based regimen with prednisone and MMF that evaluated late concentration-controlled withdrawal of CNI or MMF on renal function.

Quantitative polymerase chain reaction profiling of immunomarkers in rejecting kidney allografts for predicting response to steroid treatment.

Background: Steroid-resistant acute rejection is a risk factor for inferior renal allograft outcome.

Methods: From 873 kidney transplant recipients (1995-2005), 108 patients with a first rejection episode were selected for study using strict inclusion criteria and clinical endpoint definition. We aimed to predict response to corticosteroid treatment using gene expression of 65 transcripts.

The functional polymorphism Ala258Ser in the innate receptor gene ficolin-2 in the donor predicts improved renal transplant outcome.

Background: Innate immunity plays a role in controlling adaptive immune responses.

Methods: We investigated the clinical relevance of single nucleotide polymorphisms in 22 genes encoding innate, secreted, and signaling pattern recognition receptors in a total of 520 donor-recipient pairs of postmortem, human leukocyte antigen-DR-compatible kidney transplantations. Associations with rejection incidence were tested in an a priori randomized training set and validation set.

Randomized trial comparing late concentration-controlled calcineurin inhibitor or mycophenolate mofetil withdrawal.

Background: Early calcineurin inhibitor (CNI) withdrawal with mycophenolate mofetil (MMF) has not become routine practice, due to concerns about excess acute rejection. Therapeutic drug monitoring may be advantageous when the CNI or MMF is withdrawn.

Methods: This prospective, randomized, concentration-controlled withdrawal study enrolled 177 stable renal transplant recipients on maintenance CNI-based immunosuppression, combined with steroids and MMF.

Increased influx of myeloid dendritic cells during acute rejection is associated with interstitial fibrosis and tubular atrophy and predicts poor outcome.

Dendritic cells are key players in renal allograft rejection and have been identified as an intrinsic part of the kidney. Here we quantified and phenotyped the dendritic cell populations in well-defined biopsies of 102 patients with acute renal allograft rejection in comparison with 78 available pretransplant biopsies. There was a strong increase in BDCA-1(+) and DC-SIGN(+) myeloid, BDCA-2(+) plasmacytoid, and DC-LAMP(+) mature dendritic cells in rejection biopsies compared with the corresponding pretransplant tissue.

C4d staining in renal allograft biopsies with early acute rejection and subsequent clinical outcome.

Background And Objectives: Diffuse C4d staining in peritubular capillaries (PTCs) during an acute rejection episode (ARE) is the footprint of antibody-mediated rejection. In current clinical practice, diffuse C4d+ staining during acute rejection is regarded as an inferior prognostic sign. This case-control study investigated the prognostic role of mere C4d staining for graft outcome during an ARE in a well defined cohort of similarly ARE-treated patients.

Effect of obesity on the outcome of kidney transplantation: a 20-year follow-up.

Background: Cardiovascular disease is both a major threat to the life expectancy of kidney transplant recipients and an important determinant of late allograft loss. Obesity is an important risk factor for cardiovascular disease.

Methods: We investigated the relation between both pretransplant and 1-year posttransplant body mass index (BMI) with patient and renal graft survival in a cohort of 1810 adult patients.

Urinary properdin excretion is associated with intrarenal complement activation and poor renal function.

Background: Proteinuria predicts progressive renal failure. Next to being a progression marker, non-selective proteinuria itself is thought to be toxic to the tubulointerstitium. In proteinuric states, activation of filtered or locally produced complement is toxic for renal tubular cells and likely contributes to the progression of renal failure.

Urological complications and their impact on survival after kidney transplantation from deceased cardiac death donors.

Urological complications after kidney transplantation may result in significant morbidity and mortality. However, the incidence of such complications after deceased cardiac death (DCD) donor kidney transplantation and their effect on survival is unknown. Purpose of this study was to estimate the incidence of urological complications after DCD kidney transplantation, and to estimate their impact on survival.

Infectious complications after simultaneous pancreas-kidney transplantation: a role for the lectin pathway of complement activation.

Background: Mannose-binding lectin (MBL) is a recognition molecule of the lectin pathway of complement activation, and its serum levels are largely determined by frequently occurring polymorphisms of the MBL gene. We questioned whether MBL deficiency influences infectious complications in patients after simultaneous pancreas-kidney transplantation (SPKT).

Methods: Infectious complications in the first year after transplantation were scored retrospectively in 152 consecutive SPKT patients who received their transplant at our center between 1990 and 2005.

Low pretransplantation mannose-binding lectin levels predict superior patient and graft survival after simultaneous pancreas-kidney transplantation.

Simultaneous pancreas-kidney transplantation (SPKT) is the treatment of choice for patients with type 1 diabetes and renal failure. However, this procedure is characterized by a high rate of postoperative infections, acute rejection episodes, and cardiovascular mortality. The lectin pathway of complement activation contributes to cardiovascular disease in diabetes and may play an important role in inflammatory damage after organ transplantation.

Simpler and equitable allocation of kidneys from postmortem donors primarily based on full HLA-DR compatibility.

Background: The introduction of human leukocyte antigen (HLA)-matching in nonliving kidney transplantation has resulted into a better graft outcome, but also in an increase of waiting time, especially for patients with rare HLA phenotypes. We addressed the question of the differential influence of HLA-DR-matching versus HLA-A,B in clinical kidney transplantation.

Methods: We used Kaplan-Meier product limit method to estimate survival rates, and Cox proportional hazard regression for the estimation of relative risks (Hazard-ratios) for different variables.

Central obesity is an independent risk factor for albuminuria in nondiabetic South Asian subjects.

Objective: South Asians have a high prevalence of central obesity. When the diagnosis of diabetes is made, they have a very high risk of developing renal failure. In the current study, we explored the hypothesis that central obesity is associated with the development of renal injury, before the manifestation of diabetes.

Untreated rejection in 6-month protocol biopsies is not associated with fibrosis in serial biopsies or with loss of graft function.

Donor age, calcineurin inhibitor nephrotoxicity, and acute rejection are the most significant predictors of chronic allograft nephropathy. Protocol biopsies, both in deceased- and living-donor renal grafts, have shown that cortical tubulointerstitial fibrosis correlates with graft survival and function. The impact of not treating subclinical acute rejection (SAR) is less clear.