Ongoing projects in Renal medicine
Ongoing project
Vascular Access for Hemodialysis, a Registrybased Study with Special Focus on Differences Between Sex and Regions
Gunilla Welander, Torbjörn Linde, ext.collab. Birgitta Sigvant
Dialysis access is an area of challenge and a factor that can improve quality of hemodialysis care and reduce patient mortality. This PhD project is based on registry data in the Swedish Renal Registry. Major research questions are type of vascular access in incident hemodialysis patients and complications and survival of the different types of vascular access and factors that can influence this.
Hemodialysis and Inflammation Focusing on Complement Activation and Circulating Microparticles
Philip de Laval, Inga Soveri, Bengt Fellström, Bo Nilsson, ext. coll. Peter Garred and Tora Almquist
During dialysis treatment, the blood meets foreign surfaces. Even with today's biocompatible materials, however, reaction to the contact and inflammatory response are expected. The aim of this PhD-program is to identify processes that lead to or maintain systemic inflammation and complement activation observed in hemodialysis patients. In addition to plasma, protein deposits on used dialysis filters surfaces is studied. An ex-vivo study with an anti-FXII antibody as an anticoagulant in the dialysis circuit is planned.
Novel Cardiovascular Riskmarkers in Hemodialysis
Magnus Westerlund, Inga Soveri, Bengt Fellström, Josefin Mörtberg, Maria Eriksson Svensson, ext. coll. Niclas Eriksson, Ping-Hsun Wu , Östen Ljunggren, Torbjörn Linde and Anders Larsso
The overall aim with this PhD project is to investigate the association between novel cardiovascular biomarkers and outcomes such as all-cause death, cardiovascular death, and cardiovascular events in patients on hemodialysis. In addition, the aim is to advance the understanding on what effect a hemodialysis treatment per se actually has on cardiac damage markers, iron metabolism and other biomarkers by evaluating the effect of a single dialysis session.
IgA Nephrapathy - Basic Studies and Novel Treatment
Maria Tydén, Inga Soveri, Josefin Mörtberg, Bengt Fellström ext. coll. Mazdak Nurmi and Anders Larsson
This ongoing PhD-program, is a joint venture between Uppsala and Västerås, and explores gut reactivity, microbiota, gut permeability, urine proteomics, complement activation and progression in IgAN and is a continuation of a long-term focus on gut mucosal reactivity in IgAN. The planned studies follow a treatment study in patients with IgA nephropathy using a corticosteroid compound acting primarily in the gut (budesonide) that demonstrated reduction in proteinuria and stabilization of renal function (GFR).
Recurrence of IgAN in Renal Transplants
Jacqueline Haller, Inga Soveri, Tomas Lorant, Bengt Fellström ext. coll. Hannes Olausson and Annika Wernersson-Östman
This is new PhD-program aim to characterize patients with recurrence of IgAN after renal transplantation. The prime research question is what are the underlying mechanisms for recurrence and if there are any new means for prevention and treatment. A focus will be the influence of complement activation and the potential therapeutic role of complement inhibitors.
The Obese Kidney - Potential Mechanisms and Effects of Weight Loss
Patrik Ene, Lars Lind, Magnus Sundbom, Hans Furuland, Niclas Abrahamsson, Maria Eriksson Svensson
In this PhD-program, proposed and novel mechanisms that could be part of the development of obesity-related glomerulopathy and the impact of weight loss induced by low-calorie diet and bariatric surgery on kidney function in severely obese patients without concomitant diabetes or hypertension are evaluated. This is done in the POEM-cohort and in an exploratory single center study with a before-and-after study design where the effects on kidney function induced by rapid weigth loss induced by a combination of a 4-week standardized low-calorie diet (LCD) and bariatric surgery in an ordinary clinical setting.
Other ongoing research projects
Svensk Njurmedicinsk biobank - An Important Infrastrutoe in Future Biomarker Research
Inga Soveri
All eligible patients who are kidney-biopsied are included in a national healthcare-integrated biobank with follow-up data suitable for: 1) exploratory biomarker studies, 2) development and validation of risk assessment algorithms and 3) future clinical studies of “master protocol” design. Sample management is adapted so that analyzes of complement activation, microparticles, biological aging and various "omics" methods can be applied. Centers: Uppsala, Västerås, Gävle, Linköping, Umeå, Gothenburg, Region Skåne.
Human Artery Proteomics in Uraemia
Inga Soveri ext. coll. Jonas Bergquist, SciLife Uppsala, Bo Ek, Tomas Lorant, Peter Stenvinkel, Anna Witasp and Paul Shiels
In the development of cardiovascular disease, extensive changes take place in the function and structure of the target organs and these changes can be characterized by changes in protein type and amount of protein in the organs. In kidney transplantation, the patient's own artery (usually the external iliac artery) is perforated with a “vessel punch” in order to be able to connect the transplant's artery to the patient's. We study the protein composition of this vessel piece (which has been in a uremic environment) with the aim to identify proteins that characterize processes leading to accelerated cardiovascular disease. This knowledge can lead to new, targeted treatments that prevent cardiovascular disease in kidney patients.
Recova - Recognition and Correction of Volume Alterations
Hans Furuland, Jenny Stenberg
Achieving optimal management of fluid status is a key objective in dialysis. Recova® is a tool for early recognition and correction of volume alterations in hemodialysis patients, which combines systematic clinical assessment of fluid status with bioimpedance measurement in target weight determination. The Recova tool was develop in a former PhD project. The tool is now being implemented in clinical care and effects on patient’s quality of life (QoL), hospitalization and other parameters are being evaluated. In addition, an upscale with a staggered entry approach to other dialysis clinics in Sweden is planned, to prospectively evaluate the Recova-tool regarding fluid management in hemodialysis
Experimental Studies of Human Adipose and Muscle Tissue-focus Perirenal Tissue
Maria Eriksson Svensson, Maria Joao Pereira, Amir Sedigh
Previous research has identified adipose tissue not only as a storage place for energy, but also as a highly active endocrine organ producing and secreting several hormones but also other peptides and enzymes. This is an exploratory study to identify molecular mechanisms that may play a key role in the function of human adipose tissue and to increase our understanding of the interaction between adipose tissue and kidney - the adipo-renal axis. This is done by characterizing and exploring five different fat depots related to the kidney and muscle tissue from health kidney donors to explore similarities and differences between adipose tissue and muscle with a specific focus on brown adipose tissue.
Other available resources
Nätverket för Kliniskt Njurmedicinskt Behandlingsforskning
In 2020, a national “Clinical network for chronic kidney disease research” was initiated with a steering group of the network with representatives from all university hospitals in Sweden and representatives of the Swedish Renal Registry. Current multi-center studies within stroke anticoagulation/ prophylaxis and new treatment options för chronic kidney disease are ongoing. For more information, please contact Maria Eriksson Svensson or Hans Furuland
Biobanks and Databases
Biobanks have been collected from the AURORA and ALERT randomized controlled trials and the Århus hemodialysis cohort and have been used to analyze genomic aberrations in inflammation-related genes as well as telomere length in DNA material, and shown a striking relationship to the degree of inflammation, oxidative stress, fetuin levels and patient survival. Currently, post hoc analyses of databases and biobanks are ongoing and largely based upon new biomarkers generated from the use of PEA technology. In addition, development of risk prediction algorithms leading to development of risk predictors for renal transplant and dialysis patients are ongoing. For more information regarding these databases and biobanks, please contact Bengt Fellström.