Renal albumin filtration: alternative models to the standard physical barriers

Human kidneys produce more than 4 million litres of virtually protein-free primary urine in a lifetime. In healthy individuals, the sieving process is accomplished by the glomerular filter without the smallest sign of clogging, even in old age. How nature accomplishes this extraordinary task is a mystery, but unravelling the functioning of the glomerular filter is important. The basic principles that govern glomerular filtration are probably also true for peripheral filtering by fenestrated capillaries. In addition, understanding the sieving process is a prerequisite to understanding the pathogenesis of proteinuria (that is, the leakage of plasma proteins into the urine). Proteinuria is the hallmark of glomerular disease and a major risk factor for systemic cardiovascular complications, a fact that emphasizes the relationship between the glomerular and peripheral filtering capillaries. In this Review, we briefly summarize the major models that have been proposed for the mechanisms of glomerular filtration and discuss their strengths and limitations. A special emphasis is placed on the 'electrokinetic model' that we have proposed, a model that could potentially resolve many of the seemingly strange characteristics of the glomerular filtration barrier.