The overarching goal of the Amsterdam Dialysis Research & Innovation Center (ADRIC) is to reduce the cardiovascular burden and improve the quality of life beyond the standard of care of patients with end-stage kidney disease who are treated with dialysis. In ADRIC, researchers from Amsterdam UMC and adjoining dialysis centers (Nephrocare Diapriva, Dianet Amsterdam, Niercentrum aan de Amstel) combine their expertise and resources in order to optimize outcomes.

About

ADRIC was founded in 2022 and is a joint venture of Amsterdam UMC with multiple affiliated dialysis centers to facilitate research in patients with end stage kidney disease (ESKD). In total, approximately 400 patients are treated in these centers. ADRIC is embedded in the research institute Amsterdam Cardiovascular Sciences (ACS) and Amsterdam Public Health (APH).

Research

The research activity of Amsterdam Dialysis Research & Innovation Center works toward preventing and curing cardiovascular diseases in patients with ESKD.

1. In search of the origin

Unraveling the mechanisms of cardiovascular disease in ESKD patients with the focus on prevention. This is in combination with fundamental research as conducted within the Amsterdam Cardiovascular Sciences Research Program ‘Diabetes & Hypertensive diseases'.

2. Diagnosis & Prognosis

In the future, we aim to offer patients a more tailor made treatment with regard to dialysis modality, dialysate composition, drug prescription, dietary advice, and new blood purification techniques. Furthermore, using patient characteristics, we might be able to predict patient reported outcomes and treatment complications better. This would give us the opportunity to intervene before an adverse outcome has occurred. To achieve this goal, research and analyses in large cohorts are a necessity and are embedded in the Amsterdam Public Health Research Program ‘Health Behaviors & Chronic Diseases’.

3. Intervention & Prevention

ADRIC is the platform for experimental and clinical intervention studies with new dialysis modalities, dialysate composition, life style, diet, innovative drugs, and new blood purification techniques (e.g. apheresis and immunoadsorption). Here we study interventions directed to improvement of microcirculatory perfusion and end-organ functioning, better hemodynamic stability during and after the dialysis treatment, improved blood pressure control, prevention of thrombo-embolic, ischaemic and haemorrhagic events, and prevention of serious hemostatic derangements, including hyper or hypokalemia, dysnatremias, and acid-base disturbances among dialysis patients. Furthermore, clinical studies are aimed at prevention and treatment of cardiovascular disease, and heart failure in particular, in patients with ESKD. Finally, application of new apheresis and immunoadsorption techniques is an important focus in terms of new therapy indications, efficacy and potential adverse effects (e.g.g, acid-base disturbances). The research is embedded in the Amsterdam Cardiovascular Sciences Research Program ‘Diabetes & Hypertensive diseases'.

Team & researchers

Our team consists of nephrologists, epidemiologists, nurse practitioners, research nurses and PhD candidates various engaged in various research lines such as vascular calcification, heart failure, the effect of salts in dialysis and the effect of various dialysis modalities on adverse events and quality of life. The primary goal – an improved quantity and quality of life for dialysis patients – is shared by all teams.

Clinical investigators (nephrologists): prof. dr. Liffert Vogt, dr. Brigit van Jaarsveld, dr. Muriel Grooteman, prof. dr. Menso Nubé, dr. Lily Jakulj, dr. Camiel de Roij van Zuijdewijn, dr. Rik Olde Engberink, dr. Aegida Neradova and dr. Fenna van Breda.

Epidemiologists: dr. Brigit van Jaarsveld and dr. Camiel de Roij van Zuijdewijn.

Research nurses: Marlon van de Putte, Gertrude Wijngaarden, Claudette Promes and Marie-Louise Nelissen.

Current PhD candidates: Wafa Karar, Micky Karsten, Sabrine Chaara, Esmee Driehuis, Bas van Lieshout, Sanédy Simon.

Projects

Sodium Alignment in Hemodialysis (SALINE)
In this randomized cross-over intervention trial, we will study whether dialysate sodium alignment during hemodialysis can lower skin sodium content and thereby improve hemodynamics and quality of life. We will compare hemodialysis and hemodiafiltration with a standardized dialysate sodium concentration of 139 mmol/L with individualized dialysate sodium alignment in 26 subjects. To assess the long-term consequences of skin sodium accumulation, we will include 50 subjects in a cohort study. The study is expected to start in 2025.
DOMESTICO
DOMESTICO or the Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes is a nationwide, combined retrospective and prospective, observational cohort study that included adult patients who started with a form of dialysis. The retrospective part of DOMESTICO (2012-2017, n = ± 1300 pts) focuses on clinical outcomes of home dialysis, in particular technique failure and hospitalization, compared to in-center hemodialysis, and on identifying modifiable factors. The prospective part of DOMESTICO (2017-2022, n = ± 2000 pts) focuses on 1. Determining the effects of home dialysis on various aspects of quality of life compared to in-center hemodialysis, measured by patient reported outcome measures (PROMs); and 2. Performing a cost-effectiveness analysis of the various forms of home dialysis compared to in-center hemodialysis, which should contribute to higher value-based health care (i.e. maximum value of patient care at the best costs).
MIMOSA
The Microcirculation, dialysis MOdality and SAlt (MIMOSA) study is a randomized
cross-over trial with an anticipated inclusion of 23 participants. All
participants will be subjected to 5 different dialysis types: hemodialysis (HD)
with a dialysate sodium (NaD) equal to plasma sodium (NaP), HD with a NaD 3
mmol/L lower than NaP, isolated ultrafiltration for 30 minutes followed by HD
with a NaD equal to NaP, high-volume hemodiafiltration (hvHDF) with a NaD equal
to NaP and hvHDF with a NaD 3 mmol/L lower than NaP. The primary aim is to
assess whether differences in these modalities can be observed in the
sequestered (‘non-osmotic’) sodium content and the microcirculation.
Furthermore, we aim to investigate whether the effect on the microcirculation
is related to a potential change in the sequestered sodium content. The
inclusion is anticipated to start in the fourth quarter of 2023.
POTASSIUM STUDY
Single-blind, interventional cross-over study to analyze how potassium handling, volume and sodium status change in stable anuric chronic hemodialysis patients (CKD-5D) in response to higher dialysate potassium. Hemodialysis patients will be treated using widely used dialysate solutions as part of standard care containing potassium either 2 mmol/L or 4 mmol/L in random order. The primary outcome will be red blood cell (RBC) potassium, reflecting total body potassium. Secondary endpoints will include serum potassium, potassium removal, hyperkalemia occurrence, ECG changes, serum sodium, sodium removal, total ultrafiltration volume, total body water, and systolic blood pressure as well as changes in serum bicarbonate, insulin, and plasma aldosterone. The Potassium in dialysis study is part of the K+onsortium (Kalium Studie) funded by the Dutch Kidney foundation.
RENAL LIFECYCLE TRIAL
Sodium Glucose Transporter 2 inhibitors (SGLT2i) induce a cardiorenal protective effects independent of diabetes status and baseline eGFR in large cardiovascular outcome trials (CVOTs). Patients with severe chronic kidney disease (CKD) have thus far been excluded from these CVOTs ,while especially these patients are at high risk cardiovascular morbidity and mortality. The Renal Lifecycle trial is a trial to assess the effect of dapagliflozin (an SGLT2i) on renal and cardiovascular outcomes in patients with severe CKD. It is an investigator initiated, randomized, double blind, parallel multicenter trial conducted in the Netherlands, Belgium, Australia and Germany. Patients with an eGFR <25ml/min/1.73m2 (on a stable dose of RAAS inhibition), dialysis patients with a residual diuresis of >500ml/24h and renal transplant recipients with an eGFR <45ml/min/1.73m2 will be randomized to either dapagliflozin or placebo. The primary outcome is a combined endpoint of all-cause mortality, kidney failure and hospitalization or heart failure. . ADRIC participates in this CVOT designed and coordinated by investigators at UMC Groningen (Renal Lifecycle Trial – Renal lifecycle trial (renal-lifecycle.com).
STOP HF in PD
The STOP Heart Failure in Peritoneal Dialysis (STOP HF in PD) trial is a sub-study of the Renal Lifecycle Trial, designed and coordinated by ADRIC-investigators and funded by the Dutch Kidney Foundation. Its aim is to study the effects of dapagliflozin on cardiac function and physical functionality in patients treated with peritoneal dialysis. Cardiac ultrasound, cardiac MRI, functionality tests and measurements of CKD- and PD-associated mediators of heart failure will be performed at baseline, after 6 months and 1 year in one hundred PD-treated patients included in the Renal Lifecycle Trial. The primary outcome is the difference in change in Left Ventricular Global Longitudinal Strain (LV-GLS) at 6 months of treatment. Translational validation of clinical findings of STOP HF in PD are performed in collaboration with the Amsterdam UMC Department of Physiology, as part of the Horizon 2020 MSCA-ITN IMPROVE-PD consortium (https://improvepd.eu) in a murine cardiomyopathy model, in which mice are subjected to PD-infusions and SGLT2-inhibition, and cardiac phenotype is measured by echocardiography, cardiac MRI, pressure-volume loop recordings and histology.
PERITONEAL DIALYSIS EFFLUENT DERIVED EXTRACELLULAR VESICLES (PDE-EVS) TO ESTABLISH PD-INDUCED PERITONEAL ALTERATIONS AND CARDIOVASCULAR RISK
Extracellular vesicles (EVs) are nano-sized structures containing proteins, micro-RNAs and lipids reflecting their cells of origin and have a role in intercellular communication. EVs have been widely investigated as potential easy-accessible and stable biomarkers, particularly in inflammatory conditions. In collaboration with the Amsterdam UMC Exosomes Research Group/Cancer Center Amsterdam and ExBiome B.V. we develop a clinically applicable and robust technique to isolate and analyze the molecular cargo of PDE-EVs, in order to study PD-induced peritoneal alterations and cardiovascular risk.
DIALYSIS BIOBANK
The aim of the Amsterdam Dialysis Biobank is to increase knowledge regarding ESKD, dialysis treatment and its (cardiovascular) complications. In our biobank, incident patients treated with hemo- and peritoneal dialysis are included. To enable future research, samples of blood, urine, feces, saliva and PD-effluent are collected and stored annually along with clinical characteristics of the included patients.
TURN-Long COVID: Investigating the Cause and Treatment of Post-COVID

The cause of post-COVID remains unknown, and the symptoms vary greatly between patients. Recently, Brent Appelman, Prof. Wiersinga, and colleagues discovered autoantibodies in post-COVID patients that attack the body’s own cells. This suggests that post-COVID may be an autoimmune disease.

To test this hypothesis, they are launching the TURN-Long COVID study in collaboration with ADRIC: a randomized, placebo-controlled clinical trial that will examine whether immunoadsorption—a treatment that filters harmful autoantibodies from the blood—can reduce symptoms. The team received €1,268,643 from ZonMw for this research.

“In the TURN-Long COVID study, we screen participants for autoantibodies using a new diagnostic test. Only patients with these antibodies will participate,” explains Brent Appelman. “This precision-targeted immunotherapy can help us understand the role of autoantibodies in post-COVID and potentially open the door to other treatments, such as rituximab, daratumumab, efgartigmod, FcRn inhibitors, and intravenous immunoglobulin (IVIG).” Read more here (in Dutch).

HIV Studies: The NOVA Study and ACTHIVE Vaccination Studies

HIV Studies: The NOVA Study and ACTHIVE Vaccination Studies The NOVA study, conducted by the H-Team, investigates how early HIV treatment affects the immune system and the virus. These insights contribute to the development of new treatment strategies, such as therapeutic vaccination or broadly neutralizing antibodies, that could ultimately enable people with HIV to suppress the virus on their own without the long-term use of HIV medications. Additionally, we support the HIV vaccination program led by Prof. Dr. Rogier Sanders from Amsterdam UMC. In order to study enough immune cells, our department uses leukapheresis to harvest leukocytes.

Read more:
Cohort studie naar vroege behandeling van acute HIV-infectie – H-TEAM (in Dutch)

HIV-1 envelope trimer vaccine induces sex-associated differences in antibody responses: a phase 1 clinical trial | Nature Communications

Previous studies

HOLLANT
HOLLANT is a randomized cross-over trial in 40 prevalent dialysis patients assessing the effect of dialysis modality on intradialytic hemodynamic stability, patient well-being and organ damage. Every participant was subjected to two weeks of treatment with conventional hemodialysis (‘standard hemodialysis’; sHD), HD with cool dialysate (cHD), low-volume hemodiafiltration (lvHDF) and high-volume HDF (hvHDF). During the second week of each treatment modality, blood pressure (BP) was assessed every 15 minutes during dialysis. Furthermore, patients were asked to fill in the Dialysis Symptom Index to assess whether the complaints during dialysis differed between the four treatment types. Third and fourth, markers of organ damage and inflammation were determined. Lastly, three cardiac ultrasounds were made during the last treatment of every modality to determine difference in cardiac geometric patterns. The data collection of HOLLANT has ended. The protocol can be found here and the results of the primary analysis here.
Kinetics of extracellular vesicles during hemodialysis
Various cell types shed small particles upon activation and/or injury, so called extracellular vesicles (EVs). These EVs contain many different proteins and are too large to travers dialyzer membranes. Both the contact between circulating blood cells and the extracorporeal circuit, and recurrent hypotension during hemodialysis, predispose to micro-inflammation and cell activation, which are related to morbidity and mortality. Hence, the assessment of EVs might be a valuable tool to assess dialysis-induced adverse side-effects, not only in the dialyser but also in the body. In a recent study, we found an increase in EVs during treatment with different dialysis modalities. In a pilot study, we aim to assess the kinetics of EVs in routine HD. The results of this pilot study will enable us to determine the optimal timing and specific locations for assessment.

Events

Amsterdam UMC dialysis research & innovation center (ADRIC) invites you the their symposium where cliniciand and researchers present their first result of dialysis research to the nephrology field.

Please visit the event page for more information.

Contact

Project office ADRIC
E-mail adress: ADRIC@amsterdamumc.nl