Everolimus plus reduced calcineurin inhibitor prevents anti-HLA antibodies and humoral rejection in kidney transplant recipients: 12-month results from the ATHENA study.

Background: Studies prospectively monitoring donor-specific antibodies (dnDSAs) and their clinical impact are sparse. This substudy of ATHENA was initiated to evaluate the effect of everolimus (EVR) or mycophenolic acid (MPA) in combination with reduced calcineurin inhibitor (CNI, tacrolimus [TAC] or cyclosporine [CsA]) on the formation of human leukocyte antibodies (HLA), including dnDSA, and the impact on clinical outcomes in kidney transplant (KTx) recipients.

Methods: All eligible patients were randomized 1:1:1 to receive either EVR + TAC, EVR + CsA or MPA + TAC, with basiliximab induction plus steroids after transplantation up to Month 12.

Impact of everolimus plus calcineurin inhibitor on formation of non-HLA antibodies and graft outcomes in kidney transplant recipients: 12-month results from the ATHENA substudy.

Background: Non-human leukocyte antigen (non-HLA) antibodies including antibodies targeting Angiotensin II type 1 (AT1R) and Endothelin-1 type A (ETAR) receptors represent a topic of interest in kidney transplantation (KTx). This exploratory substudy evaluated the impact of everolimus (EVR) or mycophenolic acid (MPA) in combination with tacrolimus (TAC) or cyclosporine A (CsA) in patients with preformed non-HLA antibodies, potentially associated rejections and/or their impact on renal function over 1 year.

Methods: All eligible patients were randomized (1:1:1) before transplantation to receive either EVR/TAC, EVR/CsA, or MPA/TAC regimen.

Recommended data elements for health registries: a survey from a German funding initiative.

Background: The selection of data elements is a decisive task within the development of a health registry. Having the right metadata is crucial for answering the particular research questions. Furthermore, the set of data elements determines the registries' readiness of interoperability and data reusability to a major extent.

Excellent efficacy and beneficial safety during observational 5-year follow-up of rapid steroid withdrawal after renal transplantation (Harmony FU study).

Background: We previously reported excellent efficacy and improved safety aspects of rapid steroid withdrawal (RSWD) in the randomized controlled 1-year "Harmony" trial with 587 predominantly deceased-donor kidney transplant recipients randomized either to basiliximab or rabbit antithymocyte globulin induction therapy and compared with standard immunosuppressive therapy consisting of basiliximab, low tacrolimus once daily, mycophenolate mofetil and corticosteroids.

Methods: The 5-year post-trial follow-up (FU) data were obtained in an observational manner at a 3- and a 5-year visit only for those Harmony patients who consented to participate and covered clinical events that occurred from the second year onwards.

Results: Biopsy-proven acute rejection and death-censored graft loss rates remained low and independent of RSWD.

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.

Cross-Registry Benchmarking of Data Quality: Lessons Learned.

Feedback of data quality measures to study sites is an established procedure in the management of registries. Comparisons of data quality between registries as a whole are missing. We implemented a cross-registry benchmarking of data quality within the field of health services research for six projects.

Linking EMR Data to REDCap: Implementation in the SOLKID Register.

Secondary use, the reuse of medical patient data stored during routine care in the hospital's electronic medical records (EMR) for research purpose is common, especially for registers and pragmatic trials. Often the medical data items are copied manually from the EMR into the used research database. This process is time consuming and error prone.

Metadata Definition in Registries: What Is a Data Element?

Observational research benefits from a rich methodological foundation of registry development and operation published in international and national guidelines. Metadata management is an essential part of registry implementation based on concepts of data elements and value sets. The metadata from six German registries revealed vastly divergent interpretations of the concept of data elements.

Improved Kidney Allograft Function after Early Conversion of Fast IR-Tac Metabolizers to LCP-Tac.

Fast tacrolimus (Tac) metabolism is associated with a more rapid decline of renal function after renal transplantation (RTx). Because the pharmacokinetics of LCP-Tac (LCPT) and immediate-release Tac (IR-Tac) differ, we hypothesized that switching from IR-Tac to LCPT in kidney transplant recipients would improve the estimated glomerular filtration rate (eGFR), particularly in fast metabolizers. For proof of concept, we performed a pilot study including RTx patients who received de novo immunosuppression with IR-Tac.

The Influence of Parathyroidectomy on Osteoporotic Fractures in Kidney Transplant Recipients: Results from a Retrospective Single-Center Trial.

Kidney transplant (KTx) recipients are a high-risk population for osteoporotic fractures. We herein aim to identify the role of pre-transplant parathyroidectomy (PTX) and other modifiable factors associated with osteoporotic fractures in KTx recipients. We conducted a retrospective study involving 711 adult patients (4608 patient-years) who were transplanted at our center between January 2007 and June 2015.

Results of the prospective multicenter SoLKiD cohort study indicate bio-psycho-social outcome risks to kidney donors 12 months after donation.

The outcome after living kidney donation was assumed to be comparable to that of the general population. However, recent register studies reveal negative changes in kidney function, quality of life and fatigue. Avoiding methodological issues of previous studies, the Safety of the Living Kidney Donor (SoLKiD) cohort study analyzed the outcome of donors in a multicenter and interdisciplinary fashion.

Determination of unacceptable HLA antigen mismatches in kidney transplant recipients.

With the introduction of the virtual allocation crossmatch in the Eurotransplant (ET) region in 2023, the determination of unacceptable antigen mismatches (UAM) in kidney transplant recipients is of utmost importance for histocompatibility laboratories and transplant centers. Therefore, a joined working group of members from the German Society for Immunogenetics (Deutsche Gesellschaft für Immungenetik, DGI) and the German Transplantation Society (Deutsche Transplantationsgesellschaft, DTG) revised and updated the previous recommendations from 2015 in light of recently published evidence. Like in the previous version, a wide range of topics is covered from technical issues to clinical risk factors.

Prognostic implication of myocardial perfusion and contractile reserve in end-stage renal disease: A direct comparison of myocardial perfusion scintigraphy and dobutamine stress echocardiography.

Background: We aimed to compare the prognostic value of myocardial perfusion scintigraphy (MPS) and dobutamine stress echocardiography (DSE) in patients with end-stage renal disease (ESRD) without known coronary artery disease.

Methods: Two-hundred twenty-nine ESRD patients who applied for kidney transplantation at our centre were prospectively evaluated by MPS and DSE. The primary endpoint was a composite of myocardial infarction (MI) or all-cause mortality.

[Safety of the Living Kidney Donor - The German National Register - Development and Structure of a National Register in the Health Service Research].

The German living donor register Safety of the Living Kidney Donor - The German National Register (SOLKID-GNR) collects data of the medical and psychosocial outcome of living kidney donors. For the first time in Germany, a prospective data collection allows a scientifically based long-term analysis of how a living kidney donation influences the psychological and physical health of living kidney donors. This will contribute directly to improve the information and care of living kidney donors.

Increased renal function decline in fast metabolizers using extended-release tacrolimus after kidney transplantation.

Fast metabolism of immediate-release tacrolimus (IR-Tac) is associated with decreased kidney function after renal transplantation (RTx) compared to slow metabolizers. We hypothesized, by analogy, that fast metabolism of extended-release tacrolimus (ER-Tac) is associated with worse renal function. We analyzed data from patients who underwent RTx at three different transplant centers between 2007 and 2016 and received an initial immunosuppressive regimen with ER-Tac, mycophenolate, and a corticosteroid.

The Tacrolimus Metabolism Rate and Dyslipidemia after Kidney Transplantation.

Fast tacrolimus (Tac) metabolism is associated with reduced survival rates after renal transplantation (RTx), mainly due to cardiovascular events. Because dyslipidemia is a leading cause of cardiovascular death, we hypothesized that most RTx patients do not achieve recommended target low-density lipoprotein cholesterol (LDL-C) levels (European cardiology society guidelines) and that fast Tac metabolizers have higher dyslipidemia rates. This study included RTx recipients who received initial immunosuppression with immediate-release tacrolimus (IR-Tac), mycophenolate, and prednisolone.

Tumor Recurrence and Graft Survival in Renal Transplant Recipients with a History of Pretransplant Malignancy: A Matched Pair Analysis.

Organ scarcity demands critical decision-making regarding eligible transplant candidates and graft allocation to ensure best benefit from renal transplantation (RTx). Among the controversial relative contraindications is a history of pretransplant malignancy (PTM). While oncological outcomes of PTM-RTx recipients are well described, data on graft-specific outcome are scarce.

Soluble urokinase-type plasminogen activator receptor (suPAR) is a risk indicator for eGFR loss in kidney transplant recipients.

The prognostic significance of suPAR in various kidney diseases has recently been demonstrated. Its role in transplantation-specific outcomes is still largely unknown. Therefore, we prospectively investigated the prognostic relevance of suPAR in patients before and one year after kidney transplantation (KTx).

Case Report: Management of a Multidrug-Resistant CMV-Strain in a Renal Transplant Recipient by High-Dose CMV-Specific Immunoglobulins, Modulation in Immunosuppression, and Induction of CMV-Specific Cellular Immunity.

The management of multidrug-resistant strains of cytomegalovirus after solid organ transplantation is challenging. This case report demonstrates the successful treatment of a multidrug-resistant strain of cytomegalovirus that may represent a valuable option for problematic cases. This report illustrates the emergence of a multidrug-resistant cytomegalovirus (CMV) UL54 mutant strain in a renal transplant recipient with severe lymphopenia and thrombocytopenia.

Clinical features of BK-polyomavirus and cytomegalovirus co-infection after kidney transplantation.

BK polyomavirus (BKPyV) and cytomegalovirus (CMV) are the main viral pathogens affecting the graft and recipient outcome after allogenic kidney transplantation. It has recently been found that infection with both viruses has a greater impact on kidney graft function than a single infection. We retrospectively analyzed a cohort of 723 recipients who received kidney transplantation between 2007 and 2015 after living and postmortal donation for differences in risk and outcome parameters regarding BKPyV (DNAemia) and CMV (CMV DNAemia) co-infection compared to sole viremias and to patients without viremia.

Effect of everolimus-based drug regimens on CMV-specific T-cell functionality after renal transplantation: 12-month ATHENA subcohort-study results.

Post-transplant cytomegalovirus (CMV) infections and increased viral replication are associated with CMV-specific T-cell anergy. In the ATHENA-study, de-novo everolimus (EVR) with reduced-exposure tacrolimus (TAC) or cyclosporine (CyA) showed significant benefit in preventing CMV infections in renal transplant recipients as compared to standard TAC + mycophenolic acid (MPA). However, immunomodulatory mechanisms for this effect remain largely unknown.

Antihypertensive Treatment in Kidney Transplant Recipients-A Current Single Center Experience.

Arterial hypertension affects the survival of the kidney graft and the cardiovascular morbidity and mortality of the recipient after kidney transplantation (KTx). Thus, antihypertensive treatment is necessary for a vast majority of these patients. Long-term data on antihypertensive drugs and their effects on allograft function after KTx is still limited, and further investigation is required.

ABO-Incompatible Living Donor Kidney Transplantation in a Human Immunodeficiency Virus-Positive Recipient From a Human Immunodeficiency Virus-Positive Donor: A Case Report.

A human immunodeficiency virus (HIV) infection is no longer an absolute contraindication for solid organ transplantation, yet such a setting is still challenging and little explored because of general reservations and medical difficulties. We describe a 51-year-old man with end-stage renal failure due to polycystic kidney disease who underwent an ABO-incompatible kidney transplantation from his 49-year-old male partner. Early postoperative course revealed an episode of suspected acute rejection, which was successfully managed with a steroid pulse.

Effect of Concentration/Dose Ratio in De Novo Kidney Transplant Recipients Receiving LCP-Tacrolimus or Immediate-Release Tacrolimus: Post Hoc Analysis of a Phase 3 Clinical Trial.

BACKGROUND A previous phase 3 clinical trial in de novo adult kidney transplant recipients (NCT01187953) compared the efficacy and safety of once-daily LCP-tacrolimus (LCPT) and twice-daily immediate-release tacrolimus (IR-Tac). However, whether the rate of tacrolimus metabolism affects outcomes between LCPT and IR-Tac was not examined. MATERIAL AND METHODS Patients were initiated on 0.