Forskning - Baxter Novum
Predictors of clinical outcome in end-stage renal disease (ESRD) patients.
Peter Stenvinkel/Bengt Lindholm
Malnutrition, inflammation and atherosclerosis (MIA) and other determinants of clinical outcome in ESRD patients are investigated in collaboration with Division of Renal Medicine. This project has identified several novel risk factors for cardiovascular disease such as CRP, pro-inflammatory cytokines (IL-6), low fetuin (a potent circulating inhibitor of vascular calcification), markers of oxidative stress (such as plasmalogens and 8-OHdG), markers of endothelial dysfunction (ICAM/VCAM) and markers of wasting (low lean body mass). On the other hand, a high serum cholesterol, high homocysteine, and high BMI, predicts better survival and are examples of so called reverse epidemiology in ESRD. The impact of genetic variations are studied (see below).
Peritoneal dialysis (PD): Interactions between dialysis solutions, peritoneal membrane and systemic alterations in PD patients.
PD solutions with glucose, amino acids, dipeptides, icodextrin (glucose polymers) as osmotic agents are investigated in experimental and clinical studies as regards their effects on: peritoneal transport kinetics, peritoneal membrane function, infections, metabolic and nutritional changes. New PD solutions with alternative osmotic agents or additives (such as angiotensin receptor blockers, anti-adhesive substances and heparin) are explored. Mathematical modeling is applied to better understand diffusive and convective transport, and to predict possible consequences of altered PD fluid composition and different dialysis regimens. The impact of genetic variations on peritoneal membrane characteristics are investigated in separate studies (see below).
The impact of genetic factors on clinical outcome in ESRD.
Martin Schalling/Bengt Lindholm
Single nucleotide polymorphisms (SNPs) and other forms of genetic variations are analyzed in collaboration with Louise Nordfors and colleagues at Center for Molecular Medicine. This project has so far analyzed about 50 different candidate genes (with established or suspected influence on clinical outcome in other patient cohorts), and more than 10 genes have so far been shown to be associated with clinical outcome in ESRD patients.
Uremic toxicity: The impact of small, middle and large solutes on clinical outcome in ESRD.
The state of uremia is associated with changes in almost all cells, tissues and organs as a consequence of accumulation of small and large solutes following the decline of excretory, metabolic and endocrine functions of the diseased kidneys. Dialysis can only partly compensate for this, suggesting that large solutes such as peptides and proteins which are not dialyzable account for a major part of the residual uremic toxicity in renal patients. In addition, deficiencies or functional alterations of genes, proteosomes and protein/peptides can be of importance. We study the impact of uremia on DNA (epigenetics), RNA expression, and protein/peptides due to changes in nucleotides, lipids and amino acids/peptides/proteins as a consequence of oxidative stress, reactive carbonyls, advanced glycated end-products (AGEs) and other pathways.
Nutrition and metabolism in ESRD.
Kidney failure is associated with profound metabolic and nutritional alterations including insulin resistance, anorexia, dyslipoproteinemia, amino acid alterations and malnutrition, which are worsened by co-existing co-morbidities, medications and dialysis therapy. We study this in experimental, interventional and prospective studies.