Klemens Budde

Klemens Budde
Charité Universitätsmedizin Berlin | Charité · Department of Nephrology

Doctor of Medicine

About

920
Publications
64,378
Reads
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23,999
Citations
Citations since 2017
325 Research Items
11211 Citations
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Introduction
Klemens Budde currently works at the Department of Nephrology, Charité Universitätsmedizin Berlin. Klemens does research in Clinical Kidney Transplantation, Immunosuppression, Nephrology, Rare Kidney Diseases, Tuberous Sclerosis Complex (TSC), Databases, and Artificial Intelligence.

Publications

Publications (920)
Article
Full-text available
Context: De Novo nephrolithiasis in renal transplant can have severe consequences since renal transplantation involves a single functioning kidney with medical and anatomical specificities (heterotopic transplantation on iliac vessels, immunosuppressive treatments, and comorbidities). Objective: To systematically review all available evidence on...
Article
Full-text available
There is a need to improve personalized immunosuppression in organ transplantation to reduce premature graft loss. Biomarkers are needed to better detect rejection, asymptomatic graft injury, and under-immunosuppression. Assessment of minimal necessary exposure to guide tapering and prevent immune activation is also important. There is robust clini...
Chapter
Mit dem Ziel einer effektiven Abstoßungsprophylaxe bei akzeptablen Nebenwirkungen erhalten Transplantatempfängerinnen und -empfänger lebenslang eine immunsuppressive Therapie. Die Art der Immunsuppression hängt vom immunologischen Risiko ab, welches z. B. durch Vortransplantationen, Blutgruppenkompatibilität, Anzahl der HLA-Übereinstimmungen und Vo...
Article
Full-text available
Repeated vaccination against SARS-CoV-2 increases serological response in kidney transplant recipients (KTR) with high interindividual variability. No decision support tool exists to predict SARS-CoV-2 vaccination response to third or fourth vaccination in KTR. We developed, internally and externally validated five different multivariable predictio...
Article
Full-text available
Patient care after kidney transplantation requires integration of complex information to make informed decisions on risk constellations. Many machine learning models have been developed for detecting patient outcomes in the past years. However, performance metrics alone do not determine practical utility. We present a newly developed clinical decis...
Article
Full-text available
Development of donor-specific human leukocyte antigen (HLA) antibodies (DSA) remains a major risk factor for graft loss following organ transplantation, where DSA are directed towards patches on the three-dimensional structure of the respective organ donor’s HLA proteins. Matching donors and recipients based on HLA epitopes appears beneficial for t...
Article
Full-text available
Background De novo donor-specific HLA antibodies (dnDSA) are key factors in the diagnosis of antibody-mediated rejection (ABMR) and related to graft loss. Methods This retrospective study was designed to evaluate the natural course of dnDSA in graft function and kidney allograft survival and to assess the impact of mean fluorescence intensity (MFI...
Article
Post‐transplant diabetes mellitus (PTDM) and prediabetes (impaired glucose tolerance [IGT] and impaired fasting glucose [IFG]), are associated with cardiovascular events. We assessed the diagnostic performance of fasting plasma glucose (FPG) and HbA1c as alternatives to oral glucose tolerance test (OGTT)‐derived 2‐hour plasma glucose (2hPG) using s...
Article
Background It is known that kidney transplantation (KTx) decreases mortality rate and increases life expectancy about 10 years compared with dialysis, particularly in patients with diabetes. However, cardiovascular disease is still the most common cause of death after transplantation. Purpose The evaluation of the cardiovascular risk after success...
Article
Background: Blockade of interleukin-6 (IL-6) has emerged as a promising therapeutic option for antibody-mediated rejection. Subtherapeutic anti-IL-6 antibody level or treatment cessation following prolonged cytokine neutralization may result in proinflammatory rebound phenomena via accumulation of IL-6 and/or modulated gene expression of major com...
Article
Background: The long-term outcomes of solid organ transplantation remain suboptimal. Therefore, appropriate biomarkers are needed in addition to immunosuppressive drugs and other traditional approaches for graft monitoring to achieve personalized immunosuppression and reduce premature graft loss. Methods: Donor-derived cell-free DNA (dd-cfDNA) i...
Article
Nirmatrelvir/ritonavir (Paxlovid®) consists of a peptidomimetic inhibitor (Nirmatrelvir) of the SARS-CoV-2 main protease and a pharmacokinetic enhancer (Ritonavir). It is approved for the treatment of mild-to-moderate COVID-19. This combination of nirmatrelvir and ritonavir can mediate significant and complex drug-drug interactions (DDIs), primaril...
Article
Full-text available
Calcineurin inhibitors (CNIs) have improved short-term kidney allograft survival but are nephrotoxic and vasoconstrictive. Vasoconstriction is potentially reversible after switching from CNIs to belatacept. The kidney allograft shows optimal requirements for dynamic perfusion imaging using contrast-enhanced ultrasound (CEUS). We performed standardi...
Article
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Background Remote patient management (RPM) in heart failure (HF) patients has been investigated in several prospective randomized trials. The Telemedical Interventional Management in Heart Failure II (TIM-HF2)-trial showed reduced all-cause mortality and hospitalizations in heart failure (HF) patients using remote patient management (RPM) vs. usual...
Preprint
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Background: In the information extraction and natural language processing domain, accessible datasets are crucial to reproduce and compare results. Publicly available implementations and tools can serve as benchmark and facilitate the development of more complex applications. However, in the context of clinical text processing the number of accessi...
Article
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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...
Article
Full-text available
Early detection of kidney transplant (KT) rejection remains a challenge in patient care. Non-invasive biomarkers hold high potential to detect rejection, adjust immunosuppression, and monitor KT patients. So far, no approach has fully satisfied requirements to innovate routine monitoring of KT patients. In this two-center study we analyzed a total...
Article
Full-text available
Response to SARS-CoV-2-vaccines in kidney-transplant recipients (KTR) is severely reduced. Heterologous3rd vaccination combining mRNA and vector vaccines did not increase seroconversion at 4 weeks after vaccination, but evolution of antibody levels beyond the first month remains unknown. We have recently completed a randomized-controlled trial on h...
Conference Paper
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In recent years, machine learning for clinical decision support has gained more and more attention. In order to introduce such applications into clinical practice, a good performance might be essential, however, the aspect of trust should not be underestimated. For the treating physician using such a system and being (legally) responsible for the d...
Article
Introduction: Antibody-mediated rejection (ABMR) is a leading cause of kidney allograft failure. Its therapy continues to be challenge, and no treatment has been approved for the market thus far. Areas covered: In this article, we discuss the pathophysiology and phenotypic presentation of ABMR, the current level of evidence to support the use of...
Article
Full-text available
The immunogenicity of SARS-CoV-2 vaccines in kidney transplant recipients is limited, resulting in inadequately low serological response rates and low immunoglobulin (Ig) levels, correlating with reduced protection against death and hospitalization from COVID-19. We retrospectively examined the time course of anti-SARS-CoV-2 Ig antibody levels afte...
Preprint
Background Repeated vaccination against SARS-CoV-2 increases serological response in kidney transplant recipients (KTR) with high interindividual variability. No decision support tool exists to predict SARS-CoV-2 vaccination response in KTR. Methods We developed, internally and externally validated five different multivariable prediction models of...
Preprint
Full-text available
Patient care after kidney transplantation requires integration of complex information to make informed decisions on risk constellations. Many machine learning models have been developed for detecting patient outcomes in the past years. However, performance metrics alone do not determine practical utility. Often, the actual performance of medical pr...
Article
Full-text available
Mortality from COVID-19 among kidney transplant recipients (KTR) is high, and their response to three vaccinations against SARS-CoV-2 is strongly impaired. We retrospectively analyzed the serological response of up to five doses of the SARS-CoV-2 vaccine in KTR from 27 December 2020 until 31 December 2021. Particularly, the influence of the differe...
Article
Full-text available
Background: Obesity in the recipient is linked to inferior transplant outcome. Consequently, access to kidney transplantation (KT) is often restricted by body mass index (BMI) thresholds. Bariatric surgery (BS) has been established as a superior treatment for obesity compared to conservative measures, but it is unclear whether it is beneficial for...
Article
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Background Transplant glomerulopathy (TG) may indicate different disease entities including chronic AMR (antibody-mediated rejection). However, AMR criteria have been frequently changed, and long-term outcomes of allografts with AMR and TG according to Banff 2017 have rarely been investigated. Methods 282 kidney allograft recipients with biopsy-pr...
Article
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Clinical study endpoints that assess the efficacy of interventions in patients with chronic renal insufficiency can be adopted for use in kidney transplantation trials, given the pathophysiological similarities between both conditions. Kidney dysfunction is reflected in the glomerular filtration rate (GFR), and although a predefined (e.g., 50%) red...
Article
Full-text available
The diagnosis of acute T cell-mediated rejection (aTCMR) after kidney transplantation has considerable relevance for research purposes. Its definition is primarily based on tubulointerstitial inflammation and has changed little over time; aTCMR is therefore a suitable parameter for longitudinal data comparisons. In addition, because aTCMR is manage...
Article
Full-text available
Conditional marketing authorization (CMA) facilitates timely access to new drugs for illnesses with unmet clinical needs, such as late graft failure after kidney transplantation. Late graft failure remains a serious, burdensome, and life-threatening condition for recipients. This article has been developed from content prepared by members of a work...
Article
Full-text available
Patient-reported outcomes (PROs) that assess individuals’ perceptions of life participation, medication adherence, disease symptoms, and therapy side effects are extremely relevant in the context of kidney transplantation. All PROs are potentially suitable as primary or secondary endpoints in interventional trials that aim to improve outcomes for t...
Article
In kidney transplant recipients, late graft failure is often multifactorial. In addition, primary endpoints in kidney transplantation studies seek to demonstrate the short-term efficacy and safety of clinical interventions. Although such endpoints might demonstrate short-term improvement in specific aspects of graft function or incidence of rejecti...
Article
Full-text available
Antibody-mediated rejection (AMR) is caused by antibodies that recognize donor human leukocyte antigen (HLA) or other targets. As knowledge of AMR pathophysiology has increased, a combination of factors is necessary to confirm the diagnosis and phenotype. However, frequent modifications to the AMR definition have made it difficult to compare data a...
Article
Different types of kidney transplantations are performed worldwide, including biologically diverse donor/recipient combinations, which entail distinct patient/graft outcomes. Thus, proper immunological and non-immunological risk stratification should be considered, especially for patients included in interventional randomized clinical trials. This...
Preprint
Full-text available
Scientific publications about machine learning in healthcare are often about implementing novel methods and boosting the performance - at least from a computer science perspective. However, beyond such often short-lived improvements, much more needs to be taken into consideration if we want to arrive at a sustainable progress in healthcare. What do...
Article
Background: The most common definition of delayed graft function (DGF) relies on dialysis during the first week post-transplant and does not consider DGF severity. The impact of DGF severity on long-term graft outcome remains controversial. Methods: We analysed 627 deceased-donor kidney transplant recipients (KTRs) transplanted in 2005-2015 at o...
Article
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Interstitial fibrosis and tubular atrophy, a major cause of kidney allograft dysfunction, has been linked to premature cellular senescence. The mTOR inhibitor Rapamycin protects from senescence in experimental models, but its antiproliferative properties have raised concern early after transplantation particularly at higher doses. Its effect on sen...
Article
Full-text available
Background Antibody-mediated rejection (ABMR) is a cardinal cause of renal allograft loss. This rejection type, which may occur at any time after transplantation, commonly presents as a continuum of microvascular inflammation (MVI) culminating in chronic tissue injury. While the clinical relevance of ABMR is well recognized, its treatment, particul...
Preprint
Immunogenicity of SARS-CoV-2 vaccines in kidney transplant recipients is limited, resulting in inadequately low serological response rates and low immunoglobulin (Ig) levels, correlating with reduced protection against death and hospitalization from COVID-19. We retrospectively examined the time course of anti-SARS-CoV-2 Ig antibody levels after up...
Article
Full-text available
Timely recognition and treatment of acute kidney graft rejection is important to prevent premature graft failure. A predefined urinary marker set for acute T cell-mediated rejection (TCMR) containing 14 peptides was tested for this purpose in a multicenter in-place validation study. Methods: Three hundred twenty-nine prospectively collected and 3...
Article
Full-text available
Background: Antiviral drugs have shown little impact in patient infected with acute respiratory coronavirus 2 (SARS-CoV-2). Especially for immunocompromised persons positive for SARS-CoV-2, novel treatments are warranted. Recently, the U.S. FDA has granted an emergency use authorization (EUA) to two monoclonal antibodies (mAb) targeting the viral s...
Article
Full-text available
Transplant recipients exhibit an impaired protective immunity after SARS-CoV-2 vaccination, potentially caused by mycophenolate (MPA) immunosuppression. Recent data from autoimmune patients suggest that temporary MPA hold might significantly improve booster vaccination outcomes. We applied a fourth dose of SARS-CoV-2 vaccine to 29 kidney transplant...
Preprint
Full-text available
Mortality from COVID-19 among kidney transplant recipients (KTR) is high, and their response to three vaccinations against SARS-CoV-2 is strongly impaired. We retrospectively analyzed serological response of up to five doses of SARS-CoV-2 vaccine in KTR from December 27, 2020, until December 31, 2021. Particularly, the influence of different dose a...
Article
Full-text available
Immunosuppression increases the risk of severe coronavirus disease 2019 (COVID-19). Morbidity and mortality of this disease in kidney transplant patients are higher than in the general population. As the vaccination response of transplant patients is weak, serological monitoring was performed. In this cohort study, we analyzed the determinants of v...
Article
Full-text available
This article gives a personal, historical, account of the impact of the COVID-19 pandemic on transplantation services. The content is based on discussions held at two webinars in November 2020, at which kidney transplantation experts from prestigious institutions in Europe and the United States reflected on how the pandemic affected working practic...
Article
Full-text available
Background: Tacrolimus is the calcineurin inhibitor of choice for preventing acute rejection episodes in kidney transplant patients. However, tacrolimus has a narrow therapeutic range that requires regular monitoring of blood concentrations to minimize toxicity. A new once-daily tacrolimus formulation, LCP-tacrolimus (LCPT), has been developed, whi...
Preprint
Importance Response to SARS-CoV-2 vaccines in kidney transplant recipients (KTR) is severely reduced. Heterologous 3 rd vaccination combining mRNA and vector vaccines did not increase seroconversion at four weeks after vaccination but evolution of antibody levels beyond the first month remain unknown. Objective To assess changes in antibody respon...
Article
Full-text available
Background: Arterial stiffness and phase angle (PhA) have gained importance as a diagnostic and prognostic parameter in the management of cardiovascular disease. There are few studies regarding the differences in arterial stiffness and body composition between renal transplant recipients (RTRs) receiving belatacept (BELA) vs. calcineurin inhibitor...
Article
Objectives: To investigate the effect of extracorporeal cytokine reduction by CytoSorb (CytoSorbents, Monmouth Junction, NJ) on COVID-19-associated vasoplegic shock. Design: Prospective, randomized controlled pilot study. Setting: Eight ICUs at three sites of the tertiary-care university hospital Charité-Universitätsmedizin Berlin. Patients:...
Article
Background We compared filter survival and citrate-induced complications during continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in COVID-19 and Non-COVID-19 patients. Methods In this retrospective study we included all consecutive adult patients (n = 97) treated with RCA-CRRT. Efficacy and complications of R...
Article
Full-text available
Contrast-enhanced ultrasound (CEUS) is a widely used diagnostic tool for analyzing perfusion and characterizing lesions in several organs. However, to date, it has not been sufficiently investigated whether there is an association between CEUS findings and kidney function. This study aimed at identifying the potential relationship between kidney fu...
Preprint
Transplant recipients exhibit an impaired protective immunity after SARS-CoV-2 vaccination, potentially caused by mycophenolate (MPA) immunosuppression. Recent data from autoimmune patients suggest that temporary MPA hold might significantly improve booster vaccination outcomes. We applied a fourth dose of SARS-CoV-2 vaccine during temporary (5 wee...
Article
Full-text available
The Banff 2017 report permits the diagnosis of pure chronic antibody-mediated rejection (cAMR) in absence of microcirculation inflammation. We retrospectively investigated renal allograft function and long-term outcomes of 67 patients with cAMR, and compared patients who received antihumoral therapy (cAMR-AHT, n = 21) with patients without treatmen...
Preprint
Full-text available
To evaluate the outcomes of kidney transplantations (KTs) in the Eurotransplant Senior Program (ESP) with a focus on the very old, defined as recipients ≥75 years. This retrospective clinical study included 85 patients, who under the ESP protocol underwent deceased donor kidney transplantation from January 2010 to July 2018 at the Charité–Universit...
Article
Full-text available
Background: Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc). Autoantibodies (Abs) against endothelial cell antigens have been implicated in SSc and SRC. However, their detailed roles remain poorly defined. Pro-inflammatory cytokine interleukin-6 (IL-6) has been found to be increased in SSc, but its rol...
Article
Background Calcineurin inhibitors (CNIs) are standard of care after kidney transplantation, but they are associated with nephrotoxicity and reduced long-term graft survival. Belatacept, a selective T cell costimulation blocker, is approved for the prophylaxis of kidney transplant rejection. This phase 3 trial evaluated the efficacy and safety of co...
Article
Full-text available
Background. Donor-derived cell-free DNA (dd-cfDNA) is increasingly recognized as a valuable biomarker for acute transplant injury, with possible indications in the detection of cellular or humoral rejection and the guidance of immunosuppressive therapy. There is an ongoing debate on whether relative or absolute quantification of dd-cfDNA is more r...
Article
Background: Accumulating evidence suggests that solid organ transplant recipients, as opposed to the general population, show strongly impaired responsiveness towards standard SARS-CoV-2 mRNA-based vaccination, demanding alternative strategies for protection of this vulnerable group. Methods: In line with recent recommendations, a third dose of eit...
Article
Objective: Regional Citrate Anticoagulation (RCA) for Continuous Renal Replacement Therapy (CRRT) is widely used and leads to an excellent clottingfree filter survival. Despite strict adherence to protocols, in some cases recurrent early filter-clotting occurs. The aim of this observational study was to evaluate the underlying causes and the effica...
Article
Objective: Regional Citrate Anticoagulation (RCA) for Continuous Renal Replacement Therapy (CRRT) is widely used and leads to an excellent clottingfree filter survival. Despite strict adherence to protocols, in some cases recurrent early filter-clotting occurs. The aim of this observational study was to evaluate the underlying causes and the effica...
Article
Full-text available
Despite an increasing quality of life after renal transplantation, the number of recipients undertaking paid professional work remains relatively low. Employment after kidney transplantation became a new important marker of clinically significant health recovery. Furthermore, for social and economic reasons, returning to work and participation in s...
Poster
Full-text available
Expert survey with strategic evaluation of approach and usability of a prototype ("digital platform as a solution for improving communication in the context of waiting list management"). Usability testing of the transplant module of the "comjoodoc" platform, which enables data exchange between dialysis and transplant centers. Overall, the approach...
Preprint
Background: Accumulating evidence suggests that solid organ transplant recipients, as opposed to the general population, show strongly impaired responsiveness towards standard SARS-CoV-2 mRNA-based vaccination, demanding alternative strategies for protection of this vulnerable group. Methods: In line with recent recommendations, a third dose of eit...