BBB Seminar: Börje Haraldsson

Mechanism behind proteinuria; is there a role for the glomerular endothelium?

Börje Haraldsson,
Nephrology, Institute of Medicine, Sahlgrenska Academy and University Hospital, Gothenburg, Sweden

Glomerular disease is the most common cause of renal failure, a condition leading to increased morbidity and premature death. For the society, the costs of transplantation and dialysis are enormous, amounting to 20 billion dollars annually for the US alone, and increasing. In the last decade, our knowledge of the hereditary forms of glomerular disease has expanded due to the discovery of important podocyte-specific proteins such as nephrin, podocin, etc. However, most kidney diseases are acquired and for these conditions, such as glomerulonephritis and diabetic nephropathy, the underlying molecular mechanisms remain poorly understood. Hence therapy is unspecific, often ineffective and there are considerable side effects. Regarding the glomerular barrier, there has been a debate on glomerular size and charge selectivity. Today this debate seems to be settled and it is safe to conclude that the barrier is highly selective, in agreement with the classical finding of Brenner and coworkers. An important question is if proteinuria is caused by changes in the podocytes, in the basement membrane or in the endothelium.

In this talk, I will discuss the individual components and focus on the role of the glomerular endothelial cell and its surface layer, ESL. ESL is composed of two layers: 1. The glycocalyx consisting of membrane-bound proteoglycans and anchored proteins. 2. The somewhat thicker endothelial cell coat (ECC) with secreted proteins and glycose aminoglycans together with plasma proteins. These molecules are non-covalently linked to components of the glycocalyx and form a charged fiber matrix reducing the effective concentration of albumin and similar plasma proteins at the actual endothelial cell membrane level. The endothelial surface layer is intricate, poorly understood and likely to be much more important for glomerular permeability than hitherto appreciated.

Host: Olav Tenstad, Department of Biomedicine