The exchange across capillary walls, with reference to glomerular and peritoneal capillary permeability. Physiological, pathophysiological and clinical aspects
Principal investigator; Rippe, Bengt, Professor, MD/PhD
Clinical speciality: Renal medicine (nephrology)
Co-workers, not Lund University: Wieslander Anders
Research area/areas: Urology and Nephrology
The cells of the body require a constant "internal milieu" provided by the microcirculation, across which small solutes, macromolecules and fluid are exchanged. Disturbances in the microcirculation can be seen during shock, inflammation, in oedematous conditions etc. The basic mechanisms responsible for the microvascular exchange are still not fully elucidated.
The present project is aimed at describing the physiology of the exchanges of fluid and solutes, especially macromolecules, across capillary endothelia. We are focusing on the exchange in the peritoneum during peritoneal dialysis (PD) and on transglomerular transport of proteins and mechanisms of microalbuminuria. We have demonstrated a bimodal size-selectivity of capillary walls and developed new equations for describing transvascular protein exchange across high-selectivity endothelial pathways (small pores) and low-selectivity pathways (large pores). We have shown an unchanged or a higher transcapillary protein passage in mice lacking endothelial vesicles (no transcytosis). Based on computer simulations, we early proposed the existence of transendothelial water pathways, accounting for much of the osmotic fluid flow in PD, later identified as Aquaporin-1 (P Agre, Nobel Prize 2003).
With respect to glomerular transport, we have studied glomerular sieving (GS) of proteins and Ficoll in vivo as a function of molecular size, charge and of glomerular filtration rate (GFR). The GS of large Ficolls (radius 60-80Å) appears identical to that of large proteins. This has been utilized to study microalbuminuria in ischemia/reperfusion, trauma, sepsis, anaphylaxis, myocardial infarction, diabetes etc.
This clinical project has basic science implications. It has increased our understanding of the basic transport mechanisms for proteins across vascular walls. The three-pore model of peritoneal transport has resulted in a computer model, by which it is possible to predict peritoneal transport alterations in various physiological conditions. The proteinuria research had lead to a deeper insight into the pathophysiology of microalbuminuria and nephrotic syndrome.
Link to project homepage: http://med.lu.se/klinvetlund/njurmedicin
5 recent original publications
Venturoli D, Rippe B.
Ficoll and dextran vs. globular proteins as probes for testing glomerular permselectivity: effects of molecular size, shape, charge and deformability.
Am J Physiol, Renal Physiol. 2005; 288: F605-F613
Rippe C, Asgeirsson D, Venturoli D, Rippe A, Rippe B
Effects of glomerular filtration rate on Ficoll sieving coefficients (theta) in rats
Kidney Int. 2006; 69: 1326-1332
Rosengren B-I, Rippe A, Rippe C, Swärd K, Rippe B
Transvascular protein transport in mice lacking endothelial caveolae
Am J Physiol. 2006; 291: H1371-H1377
Axelsson J, Rippe A, Venturoli D, Swärd P, Rippe B
Effects of early endotoxemia and dextran-induced anaphylaxis on the glomerular filtration barrier in rats
Am J Physiol. Renal Physiol.. 2009; 296: F242-F248
Axelsson J, Sverrisson K, Rippe A, Fissell W, Rippe B
Reduced diffusion of charge modified, conformationally intact anionic Ficoll relative to neutral Ficoll across the rat glomerular filtration barrier in vivo
Am J Physiol. Renal physiol.. 2011; 301: F708-F712
Further publications here (new window)
|Total financing:||4.0 MSEK||Gov grant for clinical research ("ALF"):||2.3 MSEK|
|Total external financing:||1.7 MSEK||Natl and intl prioritized grants:||0.8 MSEK|