Exome sequencing reveals IFT172 variants in patients with non-syndromic cholestatic liver disease.

Background And Aim: Gene defects contribute to the aetiology of intrahepatic cholestasis. We aimed to explore the outcome of whole-exome sequencing (WES) in a cohort of 51 patients with this diagnosis.

Patients And Methods: Both paediatric (n = 33) and adult (n = 18) patients with cholestatic liver disease of unknown aetiology were eligible.

Tuberculosis dissemination in kidney transplant recipient treated with anti-CD40 monoclonal antibody: a case report.

Background: Tuberculosis (TBC) in solid organ transplant recipients represents a severe complication. The incidence among transplant recipients is higher than in the general population, and the diagnosis and treatment remain challenging. We present a case of active disseminated tuberculosis in a kidney transplant recipient treated with an anti-CD40 monoclonal antibody, who had been previously exposed to an active form of the disease, but latent tuberculosis (LTBI) was repeatedly ruled out prior to transplantation.

Predictive Potential of Flow Cytometry Crossmatching in Deceased Donor Kidney Transplant Recipients Subjected to Peritransplant Desensitization.

Recipient sensitization is a major risk factor of antibody-mediated rejection (ABMR) and inferior graft survival. The predictive effect of solid-phase human leukocyte antigen antibody testing and flow cytometry crossmatch (FCXM) in the era of peritransplant desensitization remains poorly understood. This observational retrospective single-center study with 108 donor-specific antibody (DSA)-positive deceased donor kidney allograft recipients who had undergone peritransplant desensitization aimed to analyze variables affecting graft outcome.

Rejection-associated Phenotype of De Novo Thrombotic Microangiopathy Represents a Risk for Premature Graft Loss.

Background: Thrombotic microangiopathy (TMA) significantly affects kidney graft survival, but its pathophysiology remains poorly understood.

Methods: In this multicenter, retrospective, case-control paired study designed to control for donor-associated risks, we assessed the recipients' risk factors for de novo TMA development and its effects on graft survival. The study group consists of patients with TMA found in case biopsies from 2000 to 2019 (n = 93), and the control group consists of recipients of paired kidney grafts (n = 93).

Outcome of 313 Czech Patients With IgA Nephropathy After Renal Transplantation.

The recurrence of IgA nephropathy (IgAN) after kidney transplantation occurs in 20-35% of patients. The main aim of this study is to evaluate risk factors affecting the course of IgAN after renal biopsy of native kidney and kidney transplant. We evaluated clinical parameters and histological findings at the time of biopsy of native kidney and after kidney transplantation in 313 patients with IgAN with a follow-up of up to 36 years.

The relationship between lower urinary tract dysfunctions and urinary leakage from ureterocystoneoanastomosis in male patients after kidney transplantation.

Objectives: The aim of this study was to investigate the association of lower urinary tract dysfunctions with urinary leakage from ureterocystoneoanastomosis (UCNA) after kidney transplantation.

Background: The UCNA leakage after kidney transplantation can be associated with various conditions while severe lower urinary tract dysfunctions could be one of them.

Methods: The analysis included all men who underwent kidney transplantation between January 2009 and December 2014.

Three-month course of intragraft transcriptional changes in kidney allografts with early histological minimal injury - a cohort study.

The tubulitis with/without interstitial inflammation not meeting criteria for T-cell-mediated rejection (minimal allograft injury) is the most frequent histological findings in early transplant biopsies. The course of transcriptional changes in sequential kidney graft biopsies has not been studied yet. Molecular phenotypes were analyzed using the Molecular Microscope Diagnostic System (MMDx) in 46 indication biopsies (median 13 postoperative days) diagnosed as minimal allograft injury and in corresponding follow-up biopsies at 3 months.

Molecular patterns of isolated tubulitis differ from tubulitis with interstitial inflammation in early indication biopsies of kidney allografts.

The Banff 2019 kidney allograft pathology update excluded isolated tubulitis without interstitial inflammation (ISO-T) from the category of borderline (suspicious) for acute T cell-mediated rejection due to its proposed benign clinical outcome. In this study, we explored the molecular assessment of ISO-T. ISO-T or interstitial inflammation with tubulitis (I + T) was diagnosed in indication biopsies within the first 14 postoperative days.

Developments in immunosuppression.

Purpose Of Review: In this review, we discuss achievements in immunosuppression in kidney transplant recipients published at last 18 months.

Recent Findings: Results of recent trials with everolimus in low-risk primary kidney transplant recipients suggest that lowTAC/EVR combination is noninferior and CMV and BKV viral infections are less frequent to standTAC/MPA. Iscalimab monoclonal antibody, which prevents CD40 to CD154 binding, has just recently entered phase II clinical studies in kidney transplantation.

Crossing borders to facilitate live donor kidney transplantation: the Czech-Austrian kidney paired donation program - a retrospective study.

Kidney paired donation (KPD) is a valuable tool to overcome immunological barriers in living donor transplantation. While small national registries encounter difficulties in finding compatible matches, multi-national KPD may be a useful strategy to facilitate transplantation. The Czech (Prague) and Austrian (Vienna) KPD programs, both initiated in 2011, were merged in 2015.

Molecular Fingerprints of Borderline Changes in Kidney Allografts Are Influenced by Donor Category.

The fate of transplanted kidneys is substantially influenced by graft quality, with transplantation of kidneys from elderly and expanded criteria donors (ECDs) associated with higher occurrence of delayed graft function, rejection, and inferior long-term outcomes. However, little is known about early molecular fingerprints of these events in different donor categories. Borderline changes represent the most frequent histological finding early after kidney transplantation.

Dialysis therapy is associated with peripheral marginal zone B-cell augmentation.

Chronic kidney disease stage 5 (CKD5) dialysis patients who stay long term in uremic environment often exhibit several, poorly defined, immune impairments. In this study, we assessed peripheral virus-specific effector/memory cells and subpopulations of T, B and DC cells using ELISPOT and FACS methods in 74 low-risk kidney transplant candidates without anti-HLA antibodies, prior to transplantation in pre-emptive (never experienced dialysis) and dialysis cohorts. There was difference in circulating marginal zone B cells (MZB) (IgDCD27) between dialysis patients and those receiving kidney grafts pre-emptively (P = .

Molecular Patterns Discriminate Accommodation and Subclinical Antibody-mediated Rejection in Kidney Transplantation.

Background: Accommodation in ABO-incompatible (ABOi) transplantation and subclinical antibody-mediated rejection in HLA-incompatible (HLAi) transplantation share several morphological similarities. Because the clinical long-term outcomes differ, we hypothesized different molecular processes involved in ABOi transplantation and subclinical antibody-mediated rejection.

Methods: Using Illumina Human HT-12 v4 Expression BeadChips, the whole transcriptome was evaluated based on 3-month protocol C4d+ biopsies in otherwise stable ABOi and HLAi kidney grafts, as well as in C4d-negative HLA-compatible grafts exhibiting normal histological findings.

Quantitative and qualitative changes in anti-Neu5Gc antibody response following rabbit anti-thymocyte IgG induction in kidney allograft recipients.

Antibodies of non-human mammals are glycosylated with carbohydrate antigens, such as galactose-α-1-3-galactose (α-Gal) and N-glycolylneuraminic acid (Neu5Gc). These non-human carbohydrate antigens are highly immunogenic in humans due to loss-of-function mutations of the key genes involved in their synthesis. Such immunogenic carbohydrates are expressed on therapeutic polyclonal rabbit anti-human T-cell IgGs (anti-thymocyte globulin; ATG), the most popular induction treatment in allograft recipients.

Efficacy and safety of BORTEZOMIB treatment for refractory acute antibody-mediated rejection-a pilot study.

A novel therapeutic approach to refractory acute antibody-mediated rejection (AMR) in kidney transplant recipients was applied in 23 patients based on administration of Bortezomib, intravenous corticosteroids, plasmapheresis and Rituximab. Application of Bortezomib regimen led to diminishing of donor-specific antibodies (DSA) to HLA-B (P = 0.004) and HLA-DR (P = 0.

Magnetic resonance imaging biomarkers for chronic kidney disease: a position paper from the European Cooperation in Science and Technology Action PARENCHIMA.

Functional renal magnetic resonance imaging (MRI) has seen a number of recent advances, and techniques are now available that can generate quantitative imaging biomarkers with the potential to improve the management of kidney disease. Such biomarkers are sensitive to changes in renal blood flow, tissue perfusion, oxygenation and microstructure (including inflammation and fibrosis), processes that are important in a range of renal diseases including chronic kidney disease. However, several challenges remain to move these techniques towards clinical adoption, from technical validation through biological and clinical validation, to demonstration of cost-effectiveness and regulatory qualification.

The effect of induction therapy on established CMV specific T cell immunity in living donor kidney transplantation.

Cytomegalovirus (CMV) infection influences both short and long term outcomes in immunosuppressed organ transplant recipients. The aim of this study was to evaluate the effect of different induction immunosuppression regimens on CMV specific T cell response in patients with already established CMV immunity. In 24 seropositive living donor kidney recipients, the frequency of CMV specific T cells was determined by ELISPOT (Enzyme-Linked ImmunoSpot) assay prior and 6 months after transplantation.

The Effects of Diuresis, Duration of Dialysis and Age on Lower Urinary Tract Function in Urologically Healthy Male Patients on the Waiting List for Kidney Transplant.

Purpose: This work investigated the effects of diuresis, duration of dialysis and age on lower urinary tract function in urologically healthy males on the waiting list for kidney transplant.

Materials And Methods: The study included all men who had kidney transplants at our centre between January 2009 and December 2014 who had normal urological findings prior to inclusion on the list. Diuresis, the duration of haemodialysis, age, and parameters of function of the lower urinary tract as determined by filling and voiding cystometry were evaluated.

Molecular profiling in IgA nephropathy and focal and segmental glomerulosclerosis.

The aim of the study was to characterize by molecular profiling two glomerular diseases: IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) and to identify potential molecular markers of IgAN and FSGS progression. The expressions of 90 immune-related genes were compared in biopsies of patients with IgAN (n=33), FSGS (n=17) and in controls (n=11) using RT-qPCR. To identify markers of disease progression, gene expression was compared between progressors and non-progressors in 1 year follow-up.

Steroid free immunosuppression is associated with enhanced Th1 transcripts in kidney transplantation.

Background: Steroid avoidance in immunosuppression in kidney transplantation offers several metabolic advantages, however it is associated with higher early acute rejection rate. Cellular and molecular mechanisms of this phenomenon remain poorly understood.

Methods: In this single center observational study, low-risk kidney transplant recipients randomized into large multicenter prospective ADVANCE trial with steroid avoidance/early withdrawal and center standard of care treated patients were monitored for 12months.

Soluble BAFF Cytokine Levels and Antibody-Mediated Rejection of the Kidney Allograft.

The B-cell activating factor (BAFF) cytokine has important functions for the survival and maturation of B lymphocytes, which implies that this cytokine might play a role in the development of antibody-mediated rejection (AMR) after kidney transplantation. In our study, we compared the concentrations of the soluble BAFF cytokine in kidney graft recipients with AMR and patients without rejection with the goal of testing the hypothesis whether BAFF level measurement might be useful as a diagnostic marker of AMR. The study included a cohort of 19 high-risk patients with diagnosed AMR and 17 control patients free of rejection.