The glomerular endothelial cell coat is essential for glomerular filtration

Abstract

The endothelial cell surface layer (ESL) is believed to contribute to the glomerular barrier, and the nature of its molecular structure is still largely unknown. The ESL consists of the membrane-bound glycocalyx and the loosely attached endothelial cell coat (ECC). A brief injection of hypertonic sodium chloride into the left renal artery was used to displace, elute, and collect non-covalently bound components of the renal ESL in rats. This procedure increased the fractional clearance of albumin 12-fold without detectable morphological changes as assessed by electron microscopy compared with the control group injected with isotonic saline. Mathematical modeling suggested a reduced glomerular charge density. Mass spectrometry of the renal eluate identified 17 non-covalently bound proteins normally present in the ECC. One of these proteins, orosomucoid, has previously been shown to be important for capillary permselectivity. Another protein, lumican, is expressed by glomerular endothelial cells and likely contributes to maintaining an intact barrier. Thus, the absence of one or more of these proteins causes proteinuria and illustrates the importance of the ECC in glomerular permselectivity.