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4. Recovery of dialysis patients with COVID-19: health outcomes 3 months after diagnosis in ERACODA

Author

Hemmelder, Marc H, Noordzij, Marlies, Vart, Priya, Hilbrands, Luuk B, Jager, Kitty J, Abrahams, Alferso C, Arroyo, David, Battaglia, Yuri, Ekart, Robert, Mallamaci, Francesca, Malloney, Sharon-Rose, Oliveira, Joao, Rydzewski, Andrzej, Sridharan, Sivakumar, Vogt, Liffert, Duivenvoorden, Raphaël, Gansevoort, Ron T, Franssen, Casper FM, van der Net, Jeroen B, Essig, Marie, du Buf-Vereijken, Peggy WG, van Ginneken, Betty, Maas, Nanda, van Jaarsveld, Brigit C, Bemelman, Frederike J, Klingenberg-Salahova, Farah, Heenan-Vos, Frederiek, Vervloet, Marc G, Nurmohamed, Azam, Abramowicz, Daniel, Verhofstede, Sabine, Maoujoud, Omar, Malfait, Thomas, Fialova, Jana, Melilli, Edoardo, Favà, Alexandre, Cruzado, Josep M, Perez, Nuria Montero, Lips, Joy, Krepel, Harmen, Adilovic, Harun, Hengst, Maaike, Konings, Constantijn JAM, Braconnier, Philippe, Weis, Daniel, Gellert, Ryszard, Alferes, Daniela G, Radulescu, Daniela, Zakharova, Elena V, Ambuehl, Patrice Max, Guidotti, Rebecca, Walker, Andrea, Lepeytre, Fanny, Rabaté, Clémentine, Rostoker, Guy, Marques, Sofia, Azasevac, Tijana, Majstorovic, Gordana Strazmester, Katicic, Dajana, Dam, Marc ten, Krüger, Thilo, Brzosko, Szymon, Liakopoulos, Vassilios, Zanen, Adriaan L, Logtenberg, Susan JJ, Fricke, Lutz, Kuryata, Olexandr, Slebe, Jeroen JP, ElHafeez, Samar Abd, Kemlin, Delphine, van de Wetering, Jacqueline, Reinders, Marlies EJ, Hesselink, Dennis A, van Gestel, J Kal-, Eiselt, Jaromir, Kielberger, Lukas, El-Wakil, Hala S, Verhoeven, Martine AM, Logan, Ian, Canal, Cristina, Facundo, Carme, Ramos, Ana M, Debska-Slizien, Alicja, Veldhuizen, Nicoline MH, Tigka, Eirini, Konsta, Maria Anna Polyzou, Panagoutsos, Stylianos, Postorino, Adele, Cambareri, Francesco, Matceac, Irina, Nistor, Ionut, Covic, Adrian, Groeneveld, JHM, Jousma, Jolanda, van Buren, Marjolijn, Diekmann, Fritz, Oppenheimer, Federico, Blasco, Miquel, Pereira, Tiago Assis, and dos Santos, Augusto Cesar Soares

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Kidney Disease, Patient Safety, Clinical Research, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Good Health and Well Being, Aged, Aged, 80 and over, COVID-19, COVID-19 Testing, Female, Humans, Intensive Care Units, Male, Middle Aged, Outcome Assessment, Health Care, Renal Dialysis, SARS-CoV-2, ERACODA Collaborators, dialysis, functional health status, mental health status, survival, Urology & Nephrology, Clinical sciences
Abstract

BackgroundCoronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis.MethodsWe analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression.ResultsIn 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8-6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome.ConclusionsMortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis.

Published
2022

5. Multiomic profiling of transplant glomerulopathy reveals a novel T-cell dominant subclass

Author

Cristoferi, Iacopo, Varol, Hilal, van Baardwijk, Myrthe, Rahiem, Layla, Lila, Karishma A., van den Bosch, Thierry P.P., Baan, Carla C., Hesselink, Dennis A., Kramann, Rafael, Minnee, Robert C., Mustafa, Dana A.M., Reinders, Marlies E.J., Roelen, Dave L., Shahzad-Arshad, Shazia P., Smith, Rex N., Stubbs, Andrew P., Colvin, Robert B., Rosales, Ivy A., and Clahsen-van Groningen, Marian C.

Published
2024
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19. Feasibility and Potential of Transcriptomic Analysis Using the NanoString nCounter Technology to Aid the Classification of Rejection in Kidney Transplant Biopsies

Author

Varol, Hilal, Ernst, Angela, Cristoferi, Iacopo, Arns, Wolfgang, Baan, Carla C., van Baardwijk, Myrthe, van den Bosch, Thierry, Eckhoff, Jennifer, Harth, Ana, Hesselink, Dennis A., van Kemenade, Folkert J., de Koning, Willem, Kurschat, Christine, Minnee, Robert C., Mustafa, Dana A. M., Reinders, Marlies E. J., Shahzad-Arshad, Shazia P., Snijders, Malou L. H., Stippel, Dirk, Stubbs, Andrew P., von der Thüsen, Jan, Wirths, Katharina, Becker, Jan U., and Clahsen-van Groningen, Marian C.

Published
2022
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21. #2237 Preliminary results of Protection of Renal Function after Conversion of fast IR-Tac Metabolizers to Envarsus® study (The Protect RENvarsus study)

Author

Thölking, Gerold, primary, Jehn, Ulrich, additional, Sommerer, Claudia, additional, Guthoff, Martina, additional, Avdiu, Alban, additional, Weinmann-Menke, Julia, additional, Kommer, Andreas, additional, Hesselink, Dennis, additional, Schagen, Maaike, additional, Kurschat, Christine, additional, Miglinas, Marius, additional, and Reuter, Stefan, additional

Published
2024
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29. Telemedicine for Kidney Transplant Recipients:Current State, Advantages, and Barriers

Author

Hezer, Bartu, Massey, Emma K., Reinders, Marlies E.J., Tielen, Mirjam, Van De Wetering, Jacqueline, Hesselink, Dennis A., Van Den Hoogen, Martijn W.F., Hezer, Bartu, Massey, Emma K., Reinders, Marlies E.J., Tielen, Mirjam, Van De Wetering, Jacqueline, Hesselink, Dennis A., and Van Den Hoogen, Martijn W.F.

Abstract

Telemedicine is defined as the use of electronic information and communication technologies to provide and support healthcare at a distance. In kidney transplantation, telemedicine is limited but is expected to grow markedly in the coming y. Current experience shows that it is possible to provide transplant care at a distance, with benefits for patients like reduced travel time and costs, better adherence to medication and appointment visits, more self-sufficiency, and more reliable blood pressure values. However, multiple barriers in different areas need to be overcome for successful implementation, such as recipients' preferences, willingness, skills, and digital literacy. Moreover, in many countries, limited digital infrastructure, legislation, local policy, costs, and reimbursement issues could be barriers to the implementation of telemedicine. Finally, telemedicine changes the way transplant professionals provide care, and this transition needs time, training, willingness, and acceptance. This review discusses the current state and benefits of telemedicine in kidney transplantation, with the aforementioned barriers, and provides an overview of future directions on telemedicine in kidney transplantation.

Published
2024

30. Modelling changes in the pharmacokinetics of tacrolimus during pregnancy after kidney transplantation:A retrospective cohort study

Author

Schagen, Maaike R., Ulu, Asiye Nur, Francke, Marith I., van de Wetering, Jacqueline, van Buren, Marleen C., Schoenmakers, Sam, Matic, Maja, van Schaik, Ron H.N., Hesselink, Dennis A., de Winter, Brenda C.M., Schagen, Maaike R., Ulu, Asiye Nur, Francke, Marith I., van de Wetering, Jacqueline, van Buren, Marleen C., Schoenmakers, Sam, Matic, Maja, van Schaik, Ron H.N., Hesselink, Dennis A., and de Winter, Brenda C.M.

Abstract

Aims: Pregnancy after kidney transplantation is realistic but immunosuppressants should be continued to prevent rejection. Tacrolimus is safe during pregnancy and is routinely dosed based on whole-blood predose concentrations. However, maintaining these concentrations is complicated as physiological changes during pregnancy affect tacrolimus pharmacokinetics. The aim of this study was to describe tacrolimus pharmacokinetics throughout pregnancy and explain the changes by investigating covariates in a population pharmacokinetic model. Methods: Data of pregnant women using a twice-daily tacrolimus formulation following kidney transplantation were retrospectively collected from 6 months before conception, throughout gestation and up to 6 months postpartum. Pharmacokinetic analysis was performed using nonlinear mixed effects modelling. Demographic, clinical and genetic parameters were evaluated as covariates. The final model was evaluated using goodness-of-fit plots, visual predictive checks and a bootstrap analysis. Results: A total of 260 whole-blood tacrolimus predose concentrations from 14 pregnant kidney transplant recipients were included. Clearance increased during pregnancy from 34.5 to 41.7 L/h, by 15, 19 and 21% in the first, second and third trimester, respectively, compared to prior to pregnancy. This indicates a required increase in the tacrolimus dose by the same percentage to maintain the prepregnancy concentration. Haematocrit and gestational age were negatively correlated with tacrolimus clearance (P ≤ 0.01), explaining 18% of interindividual and 85% of interoccasion variability in oral clearance.Conclusions: Tacrolimus clearance increases during pregnancy, resulting in decreased exposure to tacrolimus, which is explained by gestational age and haematocrit. To maintain prepregnancy target whole-blood tacrolimus predose concentrations during pregnancy, increasing the dose is

Published
2024

31. Polarized HLA Class I Expression on Renal Tubules Hinders the Detection of Donor-Specific Urinary Extracellular Vesicles

Author

Wu,Liang, van Heugten,Martijn, van den Bosch,Thierry, Duimel,Hans, López-Iglesias,Carmen, Hesselink,Dennis, Baan,Carla, Boer,Karin, Wu,Liang, van Heugten,Martijn, van den Bosch,Thierry, Duimel,Hans, López-Iglesias,Carmen, Hesselink,Dennis, Baan,Carla, and Boer,Karin

Abstract

Liang Wu,1,2 Martijn H van Heugten,3 Thierry PP van den Bosch,4 Hans Duimel,5 Carmen López-Iglesias,5 Dennis A Hesselink,2 Carla C Baan,2 Karin Boer2 1Department of Nephrology, the First Affiliated Hospital of Shaoyang University, Shaoyang, Hunan, People’s Republic of China; 2Erasmus MC Transplant Institute, University Medical Center Rotterdam, Department of Internal Medicine, Division of Nephrology and Transplantation, Rotterdam, the Netherlands; 3University Medical Center Rotterdam, Department of Internal Medicine, Division of Nephrology and Transplantation, Rotterdam, the Netherlands; 4Department of Pathology, University Medical Center Rotterdam, Rotterdam, the Netherlands; 5The Microscopy CORE Laboratory at the Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the NetherlandsCorrespondence: Liang Wu, Erasmus MC Transplant Institute, Department of Internal Medicine, University Medical Center Rotterdam Erasmus MC, Room No. Na-514, Doctor Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands, Tel +31 0622145029, Email l.wu.1@erasmusmc.nlPurpose: Kidney transplantation is the optimal treatment for patients with end-stage kidney disease. Donor-specific urinary extracellular vesicles (uEVs) hold potential as biomarkers for assessing allograft status. We aimed to develop a method for identifying donor-specific uEVs based on human leukocyte antigen (HLA) mismatching with the kidney transplant recipients (KTRs).Patients and Methods: Urine and plasma were obtained from HLA-A2+ donors and HLA-A2- KTRs pre-transplant. CD9 (tetraspanin, EV marker) and HLA-A2 double-positive (CD9+ HLA-A2+) EVs were quantified using isolation-free imaging flow cytometry (IFCM). Healthy individuals’ urine was used to investigate CD9+ HLA-class-I+ uEV quantification using IFCM, time-resolved fluoroimmunoassay (TR-FIA), and immunogold staining cryo-electron microscopy (cryo-EM). Culture-derived CD9+ HLA-class-I+ EVs were spiked into the urine to investigate u

Published
2024

32. Modifying Tacrolimus-related Toxicity After Liver Transplantation Comparing Life Cycle Pharma Tacrolimus Versus Extended-released Tacrolimus:A Multicenter, Randomized Controlled Trial

Author

Mulder, Midas B., van Hoek, Bart, Polak, Wojtek G., Alwayn, Ian P.J., de Winter, Brenda C.M., Murad, Sarwa Darwish, Verhey-Hart, Elke, Elshove, Lara, Erler, Nicole S., Hesselink, Dennis A., den Hoed, Caroline M., Metselaar, Herold J., Mulder, Midas B., van Hoek, Bart, Polak, Wojtek G., Alwayn, Ian P.J., de Winter, Brenda C.M., Murad, Sarwa Darwish, Verhey-Hart, Elke, Elshove, Lara, Erler, Nicole S., Hesselink, Dennis A., den Hoed, Caroline M., and Metselaar, Herold J.

Abstract

Background:The aim of this open-label, multicenter, randomized controlled study was to investigate whether the life cycle pharma (LCP)-tacrolimus compared with the extended-release (ER)-tacrolimus formulation results in a difference in the prevalence of posttransplant diabetes, hypertension and chronic kidney disease (CKD) at 12 mo after liver transplantation.Methods:Patients were 1:1 randomized to either of the 2 tacrolimus formulations. The primary endpoint was defined as a composite endpoint of any of 3 events: sustained (>3 mo postrandomization) posttransplant diabetes, new-onset hypertension, and/or CKD, defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 for >3 m during the follow-up.Results:In total, 105 patients were included. In the intention-to-treat analysis, a statistically significant lower proportion of liver transplant recipients in the LCP-tacrolimus group reached the composite primary endpoint at 12 mo compared with the ER-tacrolimus group (50.9% [27/53], 95% confidence interval [CI], 37.9%-63.9% versus 71.2% [37/52], 95% CI, 57.7%-81.7%; risk difference: 0.202; 95% CI, 0.002-0.382; P = 0.046). No significant difference was found in the per protocol analysis. In the intention-to-treat and per protocol population, fewer liver transplant recipients in the LCP-tacrolimus group developed CKD and new-onset hypertension compared with the ER-tacrolimus group. No differences in rejection rate, graft and patient survival were found. Conclusions:A statistically significant and clinically relevant reduction in the prevalence of the composite primary endpoint was found in the LCP-tacrolimus group compared with the ER-tacrolimus group in the first year after liver transplantation with comparable efficacy.

Published
2024

33. Tissue-resident memory T cells in human kidney transplants have alloreactive potential

Author

Hullegie-Peelen, Daphne M., Tejeda-Mora, Hector, Dieterich, Marjolein, Heidt, Sebastiaan, Bindels, Eric M.J., Hoogduijn, Martin J., Hesselink, Dennis A., Baan, Carla C., Hullegie-Peelen, Daphne M., Tejeda-Mora, Hector, Dieterich, Marjolein, Heidt, Sebastiaan, Bindels, Eric M.J., Hoogduijn, Martin J., Hesselink, Dennis A., and Baan, Carla C.

Abstract

The extent to which tissue-resident memory T (TRM) cells in transplanted organs possess alloreactivity is uncertain. This study investigates the alloreactive potential of TRM cells in kidney explants from 4 patients who experienced severe acute rejection leading to graft loss. Alloreactive T cell receptor (TCR) clones were identified in pretransplant blood samples through mixed lymphocyte reactions, followed by single-cell RNA and TCR sequencing of the proliferated recipient T cells. Subsequently, these TCR clones were traced in the TRM cells of kidney explants, which were also subjected to single-cell RNA and TCR sequencing. The proportion of recipient-derived TRM cells expressing an alloreactive TCR in the 4 kidney explants varied from 0% to 9%. Notably, these alloreactive TCRs were predominantly found among CD4+ and CD8+ TRM cells with an effector phenotype. Intriguingly, these clones were present not only in recipient-derived TRM cells but also in donor-derived TRM cells, constituting up to 4% of the donor population, suggesting the presence of self-reactive TRM cells. Overall, our study demonstrates that T cells with alloreactive potential present in the peripheral blood prior to transplantation can infiltrate the kidney transplant and adopt a TRM phenotype.

Published
2024

37. Delayed Graft Function After Kidney Transplantation: The Role of Residual Diuresis and Waste Products, as Oxalic Acid and Its Precursors.

Author

Hospers, Gideon Post, Visser, Wesley J., Verhoeven, Jeroen G. H. P., Laging, Mirjam, Baart, Sara J., Mertens zur Borg, Ingrid R. A. M., Hesselink, Dennis A., de Mik-van Egmond, Anneke M. E., Betjes, Michiel G. H., van Agteren, Madelon, Severs, David, van de Wetering, Jacqueline, Zietse, Robert, Vos, Michel J., Kema, Ido P., Kho, Marcia M. L., Reinders, Marlies E. J., and Roodnat, Joke I.

Subjects
OXALIC acid, WASTE products, KIDNEY physiology, LOGISTIC regression analysis, GLYCOLIC acid
Abstract

Delayed graft function (DGF) after kidney transplantation heralds a worse prognosis. In patients with hyperoxaluria, the incidence of DGF is high. Oxalic acid is a waste product that accumulates when kidney function decreases. We hypothesize that residual diuresis and accumulated waste products influence the DGF incidence. Patients transplanted between 2018-2022 participated in the prospective cohort study. Pre-transplant concentrations of oxalic acid and its precursors were determined. Data on residual diuresis and other recipient, donor or transplant related variables were collected. 496 patients were included, 154 were not on dialysis. Oxalic acid, and glyoxylic acid, were above upper normal concentrations in 98.8%, and 100% of patients. Residual diuresis was ≤150 mL/min in 24% of patients. DGF occurred in 157 patients. Multivariable binary logistic regression analysis demonstrated a significant influence of dialysis type, recipient BMI, donor type, age, and serum creatinine on the DGF risk. Residual diuresis and glycolic acid concentration were inversely proportionally related to this risk, glyoxylic acid directly proportionally. Results in the dialysis population showed the same results, but glyoxylic acid lacked significance. In conclusion, low residual diuresis is associated with increased DGF incidence. Possibly accumulated waste products also play a role. Pre-emptive transplantation may decrease the incidence of DGF. [ABSTRACT FROM AUTHOR]

Published
2024
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38. Challenges for the improvement of valganciclovir prophylaxis in solid organ transplantation and the possible role of therapeutic drug monitoring in adults.

Author

Vugt, Lukas K., Hesselink, Dennis A., and Winter, Brenda C. M.

Abstract

Cytomegalovirus (CMV) infection frequently occurs after solid organ transplantation and is associated with an increased morbidity and mortality. Fortunately, the development of valganciclovir prophylaxis has lowered the incidence of CMV infection and its complications in immunosuppressed solid organ transplant recipients. However, breakthrough infections during valganciclovir prophylaxis and late CMV infection after cessation of valganciclovir prophylaxis still occur with the current prophylactic strategy. Additionally, valganciclovir resistance has emerged among CMV strains, which complicates the treatment of CMV infections. Furthermore, the use of valganciclovir is associated with myelotoxicity, which can lead to the premature withdrawal of prophylaxis. It is important to address these current issues in order to improve the standard care after solid organ transplantation. This paper will therefore discuss the clinical practice of valganciclovir prophylaxis, elaborate on its issues and suggest how to improve the current prophylactic strategy with a possible role for therapeutic drug monitoring. [ABSTRACT FROM AUTHOR]

Published
2024
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42. Patterns of the Within-Host Evolution of Human Norovirus in Immunocompromised Individuals and Implications for Treatment

Author

Izquierdo-Lara, Ray, primary, Villabruna, Nele, additional, Hesselink, Dennis A., additional, Schapendonk, Claudia M.E., additional, Ribó Pons, Sol, additional, Meier, Jenny I.J., additional, Goodfellow, Ian, additional, Dalm, Virgil, additional, Fraaij, Pieter L. A., additional, van Kampen, Jeroen, additional, Koopmans, Marion, additional, and Graaf, Miranda de, additional

Published
2024
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44. Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19)

Author

van Kampen, Jeroen J. A., van de Vijver, David A. M. C., Fraaij, Pieter L. A., Haagmans, Bart L., Lamers, Mart M., Okba, Nisreen, van den Akker, Johannes P. C., Endeman, Henrik, Gommers, Diederik A. M. P. J., Cornelissen, Jan J., Hoek, Rogier A. S., van der Eerden, Menno M., Hesselink, Dennis A., Metselaar, Herold J., Verbon, Annelies, de Steenwinkel, Jurriaan E. M., Aron, Georgina I., van Gorp, Eric C. M., van Boheemen, Sander, Voermans, Jolanda C., Boucher, Charles A. B., Molenkamp, Richard, Koopmans, Marion P. G., Geurtsvankessel, Corine, and van der Eijk, Annemiek A.

Published
2021
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