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  • Review Article
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Renal albumin filtration: alternative models to the standard physical barriers

Nature Reviews Nephrology volume 9, pages 266–277 (2013)Cite this article

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Abstract

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.

Key Points

  • The functioning of the glomerular filter is still not completely understood

  • The glomerular filter is an excellent model system for filtering capillaries

  • Several models for glomerular filtration have been proposed and have made major contributions to our understanding of glomerular filtration

  • The electrokinetic model proposes that a local electrical field is established across the glomerular filter by filtration (that is, 'streaming potential'); this electrical field prevents plasma proteins from entering or crossing the glomerular filter

  • The electrokinetic model can potentially provide mechanistic explanations to several as yet unresolved characteristics of the glomerular filtration barrier (GFB)

  • A large body of experimental data has been published that is compatible with the notion of a notable streaming potential across the GFB, but more studies are needed

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Figure 1: The filtering glomerulus.
Figure 2: The electrokinetic model.
Figure 3: Charge selectivity.
Figure 4: Concentration polarization in multilayered filter systems.
Figure 5: Schematic of the pore model.
Figure 6: Schematic of the gel hypothesis.
Figure 7: The gel permeation hypothesis.

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Acknowledgements

For reasons of clarity, many important details for all models had to be omitted from this Review. In addition, we have tried to phrase the major statements in such a way that makes them rather short and easily understandable, although again, this endeavour might have resulted in insufficient acknowledgement of the huge amount of intellectual and physical work that has been invested into the development of these models. The authors' work is supported by a Boost Fund OPBo45 of the Excellence Initiative by the German Federal and State Governments (DFG), the NephCure Foundation (F001), the German Ministry for Science and Education (BMBF, 01 GN 0804), TP17 SFB/Transregio 57 of the DFG and a START grant by the Medical Faculty of the RWTH Aachen. M. J. Moeller is a member of the SFB/Transregio 57 DFG consortium “Mechanisms of organ fibrosis”.

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  1. Department of Nephrology and Clinical Immunology, RWTH University Hospital, Aachen University, Pauwelsstrasse 30, Aachen, 52074, Germany

    Marcus J. Moeller & Verena Tenten

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M. J. Moeller and V. Tenten researched data for article, contributed to the discussion of content, and reviewed/edited the manuscript before submission. M. J. Moeller wrote the article.

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Correspondence to Marcus J. Moeller.

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Moeller, M., Tenten, V. Renal albumin filtration: alternative models to the standard physical barriers. Nat Rev Nephrol 9, 266–277 (2013). https://doi.org/10.1038/nrneph.2013.58

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