Dickkopf 3 as a New Monitoring Tool for Kidney Function After Living Kidney Donation.

Even today, a non-invasive biomarker to identify donors with enhanced risk for renal impairment is missing. Dickkopf 3 (DKK3) can cause tubulointerstitial fibrosis and is associated with rapid eGFR loss. The aim of our work was to analyze whether DKK3 can be used as a non-invasive alert marker for an increased risk of loss of kidney function in living kidney donors (LKDs).

Serum IL-6 predicts risk of kidney transplant failure independently of immunological risk.

Interleukin-6 (IL-6) is an important immune mediator and a target for novel antibody therapies. In this study, we aimed to determine whether serum IL-6 levels are associated with immunological risk, allograft rejection and outcomes in kidney transplant (Ktx) patients. We retrospectively analyzed the data of 104 patients who underwent Ktx at our center between 2011 and 2015.

[Lupus nephritis and associated thrombotic microangiopathy].

Lupus nephritis represents the most common manifestation of lupus of the solid organs and is associated with an increased risk of chronic kidney disease. The co-occurrence of lupus nephritis and thrombotic microangiopathy is described to be rare but implies the risk of fatal organ dysfunction. We report three patients in whom these two disease entities occurred in parallel, necessitating intensive immunosuppressive therapy, including complement blockade.

Cardiovascular Risk Factor Control in 70- to 95-Year-Old Individuals: Cross-Sectional Results from the Population-Based AugUR Study.

Cardiovascular risk factors such as high glucose, LDL-cholesterol, blood pressure, and impaired kidney function are particularly frequent in old-aged individuals. However, population-based data on the extent of cardiovascular risk factor control in the old-aged population is limited. AugUR is a cohort of the mobile "70+"-year-old population of/near Regensburg, recruited via population registries.

Factors influencing the time-intensity curve analysis of contrast-enhanced ultrasound in kidney transplanted patients: Toward a standardized contrast-enhanced ultrasound examination.

Background: Time-intensity curve analysis (TIC analysis) based on contrast-enhanced ultrasound (CEUS) provides quantifiable information about the microcirculation of different tissues. TIC analysis of kidney transplantations is still a field of research, and standardized study protocols are missing though being mandatory for the interpretation of TIC parameters in the clinical context. The aim of this study was to evaluate the impact of different sizes and forms of regions of interest (ROIs) on the variance of different TIC parameters and the level of interoperator variance between the different ROI methods in kidney transplantations.

Dickkopf 3-A New Indicator for the Deterioration of Allograft Function After Kidney Transplantation.

Evidence of tubular atrophy and interstitial fibrosis is prognostically unfavorable and associated with a premature graft loss after kidney transplantation. Recently, Dickkopf 3 (DKK3), a profibrotic glycoprotein released by stressed tubular epithelial cells, has been identified to cause IF/TA by regulating the Wnt/β-catenin signaling and seems to engage a T-cell response. The aim of our study was to determine if a correlation between DKK3 and graft function exists and if DKK3 could be a new indicator to identify patients at risk for a deterioration in graft function.

A Prospective Multicenter Trial to Evaluate Urinary Metabolomics for Non-invasive Detection of Renal Allograft Rejection (PARASOL): Study Protocol and Patient Recruitment.

In an earlier monocentric study, we have developed a novel non-invasive test system for the prediction of renal allograft rejection, based on the detection of a specific urine metabolite constellation. To further validate our results in a large real-world patient cohort, we designed a multicentric observational prospective study (PARASOL) including six independent European transplant centers. This article describes the study protocol and characteristics of recruited better patients as subjects.

Monitoring B cell alloresponses in rats.

Antibody-mediated rejection is a major cause of graft failure in organ transplantation. For this reason, B cell responses are of particular interest to transplantation research. Rats are important model organisms for transplant studies, but B cell alloimmune assays and B cell subset markers are poorly established in rats.

Renal Recovery after the Implementation of an Electronic Alert and Biomarker-Guided Kidney-Protection Strategy following Major Surgery.

The facilitation of early recovery of acute kidney injury (AKI) is an important step to improve outcome, particularly because of the limited therapeutic interventions currently available for AKI. The combination of an electronic alert and biomarker-guided kidney-protection strategy implemented in the routine care may have an impact on the incidence of early complete reversal of AKI after major non-cardiac surgery. We studied 294 patients in two cohorts before ( = 151) and after protocol implementation ( = 143).

B-cell activating factor BAFF as a novel alert marker for the immunological risk stratification after kidney transplantation.

The B cell activating factor BAFF has gained importance in the context of kidney transplantation due to its role in B cell survival. Studies have shown that BAFF correlates with an increased incidence of antibody-mediated rejection and the development of donor-specific antibodies. In this study, we analyzed a defined cohort of kidney transplant recipients who were treated with standardized immunosuppressive regimens according to their immunological risk profile.

Disruption of Tfh:B Cell Interactions Prevents Antibody-Mediated Rejection in a Kidney Transplant Model in Rats: Impact of Calcineurin Inhibitor Dose.

We aimed to investigate the mechanisms of humoral immune activation in ABMR using a MHC-mismatched rat kidney transplant model. We applied low dose cyclosporine A (loCNI) to allow donor-specific antibody (DSA) formation and rejection and high dose cyclosporine A (hiCNI) for non-rejection. DSA and leukocyte subsets were measured by flow cytometry.

Sonographic 3-D Power Doppler Imaging Enhances Rapid Assessment of Morphologic and Pathologic Arteriovenous Fistula Variations.

Early detection of pathologic variations in an arteriovenous fistula (AVF) is essential for preventing fistula dysfunction in individuals undergoing hemodialysis. This study aimed to evaluate the clinical applicability of 3-D tomographic ultrasound (tUS) for rapid and simple visualization of AVF morphology and pathology. We assessed 53 AVFs in 50 consecutive patients using 3-D tUS including secondary, blinded reading.

B Cell Activating Factor (BAFF) Is Required for the Development of Intra-Renal Tertiary Lymphoid Organs in Experimental Kidney Transplantation in Rats.

Intra-renal tertiary lymphoid organs (TLOs) are associated with worsened outcome in kidney transplantation (Ktx). We used an anti-BAFF (B cell activating factor) intervention to investigate whether BAFF is required for TLO formation in a full MHC-mismatch Ktx model in rats. Rats received either therapeutic immunosuppression (no rejection, NR) or subtherapeutic immunosuppression (chronic rejection, CR) and were sacrificed on d56.

Safe Long-Term Outcome After Kidney Donation in Older Donors: A Single-Center Experience.

BACKGROUND Declining numbers of deceased donors and prolonged waiting time emphasize the importance of living kidney donation. Furthermore, because of the changing age structures with increasingly older recipients, the question of acceptance of older donors is becoming more relevant. However, sufficient long-term outcome data, especially for older donors - including histopathological analysis - are lacking.

Cyclophosphamide for salvage therapy of chronic graft-versus-host disease: a retrospective analysis.

We retrospectively analyzed the safety and efficacy of cyclophosphamide (cyclo) for salvage treatment of chronic graft-versus-host disease (cGvHD) and cGvHD-associated (glomerulo-)nephritis at our center between 01/2010 and 11/2019. We identified 13 patients (pts) receiving cyclo for treatment of moderate (3/13) and severe (6/13) steroid-refractory cGvHD, cGvHD-associated (glomerulo-)nephritis (3/13), or vasculitis-like CNS manifestation of cGvHD (1/13). Cyclo was started on median day 509 (range 42-8193) after cGvHD onset; the median duration of application was 153 days (range 14-486) with 2/13 currently continuing treatment.

Contrast-Enhanced Ultrasonography as a Novel Method for the Dynamic Visualization of Blood Flow and Fiber Blockage in Dialyzers: A Feasibility Study.

The capillary dialyzer represents the central element of the extracorporeal blood circuit of a therapy system for hemodialysis. The aim of this study was to assess the blood-flow characteristics of dialyzers with the help of modern ultrasound techniques. Five brand-new dialyzers (FX80 classix, Fresenius Medical Care, Bad Homburg, Germany) and five dialyzers after a dialysis session were analyzed by different ultrasound techniques to detect functional and structural changes.

Regulatory cell therapy in kidney transplantation (The ONE Study): a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials.

Background: Use of cell-based medicinal products (CBMPs) represents a state-of-the-art approach for reducing general immunosuppression in organ transplantation. We tested multiple regulatory CBMPs in kidney transplant trials to establish the safety of regulatory CBMPs when combined with reduced immunosuppressive treatment.

Methods: The ONE Study consisted of seven investigator-led, single-arm trials done internationally at eight hospitals in France, Germany, Italy, the UK, and the USA (60 week follow-up).

[Successful rituximab treatment of recurrent glomerulonephritis associated with antibodies against the glomerular basement membrane].

This article presents a case of recurrent anti-GBM disease (with antibodies against the glomerular basement membrane [GBM]) in a 17-year-old patient successfully treated with rituximab. Kidney biopsy with detection of linear deposition of immunoglobulin G (IgG) along the basement membrane is the diagnostic gold standard, which should be accompanied by serological testing. However, standard assays for the detection of anti-GBM antibodies have a high rate of false-negative results.

Anti-BAFF Treatment Interferes With Humoral Responses in a Model of Renal Transplantation in Rats.

Background: B-cell-activating factor (BAFF) is associated with donor-specific antibodies (DSA) and poorer outcomes after renal transplantation (RTx). We examined the effects of anti-BAFF treatment on B cells, expression of costimulatory molecules and cytokines, germinal centers (GCs), and DSA formation in an RTx model in rats.

Methods: Anti-BAFF antibody was injected on days 3, 17, 31, and 45 after allogeneic RTx.

Clinical use of [TIMP-2]•[IGFBP7] biomarker testing to assess risk of acute kidney injury in critical care: guidance from an expert panel.

Background: The first FDA-approved test to assess risk for acute kidney injury (AKI), [TIMP-2]•[IGFBP7], is clinically available in many parts of the world, including the USA and Europe. We sought to understand how the test is currently being used clinically.

Methods: We invited a group of experts knowledgeable on the utility of this test for kidney injury to a panel discussion regarding the appropriate use of the test.

Analysis of Luminex-based Algorithms to Define Unacceptable HLA Antibodies in CDC-crossmatch Negative Kidney Transplant Recipients.

Background: HLA-specific antibodies detected by solid phase assays are increasingly used to define unacceptable HLA antigen mismatches (UAM) before renal transplantation. The accuracy of this approach is unclear.

Methods: Day of transplant sera from 211 complement-dependent cytotoxicity crossmatch-negative patients were retrospectively analyzed for donor-specific anti-HLA antibodies (DSA) using Luminex technology.

Renal allograft rejection, lymphocyte infiltration, and de novo donor-specific antibodies in a novel model of non-adherence to immunosuppressive therapy.

Background: Non-adherence has been associated with reduced graft survival. The aim of this study was to investigate the immunological mechanisms underlying chronic renal allograft rejection using a model of non-adherence to immunosuppressive therapy. We used a MHC (major histocompatibility complex) -mismatched rat model of renal transplantation (Brown Norway to Lewis), in which rats received daily oral cyclosporine A.