Inflammatoriska njursjukdomar
Research in Renal Disease and Uremia
Head of the research group is prof Bengt Fellström
The Renal Unit of the Department of Medical Sciences has a long tradition of clinical and experimental research, which focuses on pathogenesis and treatment of renal disease, development of extracorporeal treatments and medical long-term complications in chronic kidney disease (CKD), dialysis and renal transplantation. A large number of research students have passed through the unit and completed their PhD theses.
Cardiovascular complications
Cardiovascular disease (CVD) is extremely common in patients with renal insufficiency, which includes dialysis and renal transplant patients. Our efforts are targetting the importance of endothelial dysfunction, vascular calcification and stiffness, oxidative stress, inflammation and immune dysregulation as contributing factors to the high rate of CVD. The most recent studies relate to systemic inflammation in ureamia, its relationship to oxidative stress , shortening of telomere nucleoproetin and subsequent influence on patient survival in uremia. Such studies have been performed in several subgroups of renal patients throughout the years. The important part of our efforts is treatment studies, which to a large extent have been initiated from our own unit. Such studies include the ALERT trial in renal transplant patients, the AURORA trial in hemodialysis patients, the CORD in hemo-and peritoneal patients and the SHARP trial in preuremic and dialysis patients.
IgA nephropathy
We are currently looking into the importance of gastrointestinal hyperreactivity to alimentary antigens. The connection between gastrointestinal immune reactivity and subsequent development of IgA nephropathy is investigated. Furthermore, pilot studies are done in patients with early IgA nephropathy using a corticosteroid compound acting primarily in the gut (budesonide). The pilot study has been finished which confirmed the hypothesis and we are soon entering a randomized control study along the same lines.
Chronic allograft nephropathy
We have a substantial track record on both clinical and experimental studies in chronic allograft nephropathy (CAN). We have demonstrated upregulation of growth factors in CAN and also targeted metabolic abnormalities as progression factors of CAN. We are presently investigating early markers of CAN in biopsies, based upon findings from Tissue Micro Array investigations in lost grafts. Along with identification of epitopes on inflammatory cell infiltrate, we also target growth factors and receptors, viral antigens, metalloproteinases, adhesion molecules in the search for early markers of CAN. Furthermore, a large number of treatment studies have been done in experimental models of CAN and we have also finished a statin study in CAN patients. Presently we are participating in three different treatment protocols which include switching of immunosuppressive regimen from calcineurine-based treatment to mycophenolate or mTOR inhibitors.
Genomic studies
Superb biobanks have been collected with genomic materials from patients participating in the ALERT trial, the AURORA trial and the MIMICK trial. We are now in the process of analyzing genomic abnormalities and relationships to CVD and CAN in the ALERT trial. Forthcoming studies with genomic material from the AURORA trial will prospectively be analyzed and related to the excellent clinical data base which is being collected. In genomic material from the MIMICK study we have analyzed 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, fetuinlevels and patient survival in the MIMICK trial.
For additional information please contact Bengt Fellström, bengt.fellstrom@medsci.uu.se.
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