Albuminuria, Wherefore Art Thou?

Abstract

No concept in kidney physiology raises as much interest and debate as proteinuria. All agree that the glomerular capillary wall is a highly selective barrier that restricts the passage of plasma proteins—thus its moniker the “glomerular filtration barrier” (GFB). Albumin is the most abundant plasma protein, and significant albuminuria is considered “selective glomerular proteinuria,” in contrast to the low molecular weight proteinuria that is classically linked to tubular abnormalities. Although most attention has been focused on GFB abnormalities as being responsible for albuminuria, Comper et al. 1 continue to present evidence for a tubular origin, with the latest appearing in this issue of JASN .2 The view they advocate is in stark disagreement with long-accepted dogma of kidney physiology and pathophysiology, but if these investigators are correct, then there would be a major shift in the way proteinuric kidney diseases are viewed and, most important, treated. Inherent in the hypothesis of a tubular origin for proteinuria is the claim that albumin's glomerular sieving coefficient (GSC) is high, at 0.02 to 0.04. This means that 2 to 4% of the albumin molecules subjected to the GFB cross into the glomerular filtrate. This estimate is approximately 50 times higher than the widely accepted GSC of approximately 0.0006.3 The difference between these values is staggering; if the higher value is correct, then it means that in normal rats (GFR of 2 ml/min), 2 to 4 g/d albumin would be filtered, as opposed to …