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Podocytes are key—although albumin never reaches the slit diaphragm

Nature Reviews Nephrology volume 10, page 180 (2014)Cite this article

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We would like to thank Dr Comper for his correspondence on our Review (Renal albumin filtration: alternative models to the standard physical barriers. Nat. Rev. Nephrol. 9, 266–277; 2013)1 and the others in the Nature Reviews Nephrology collection, which raises two important issues that must be addressed (Albuminuria is controlled primarily by proximal tubules. Nat. Rev. Nephrol. 28 January 2014; doi:10.1038/nrneph.2013.58-c1).2

Firstly, Dr Comper states that “Nephrology students who read these articles would get the incorrect impression that the glomerulus and/or podocytes are central to development of albuminuria.” Contrary to what Comper proposes, the majority of researchers agree that the primary filtrate is virtually free of albumin; that is, the glomerular sieving coefficient (GSC) of albumin is extremely low (close to 0.001).3,4 Several lines of evidence support this position.1,3 For example, micropuncture studies in the rat kidney have demonstrated very low albumin concentrations in the primary filtrate. In cooled or fixed isolated perfused kidney, cubilin/megalin knockout mice or human patients with Fanconi syndrome, only very little protein is excreted in the urine (<1 g albumin per day in humans). Additionally, filtered protein has been observed in Bowman's space in histological sections only in proteinuric rodents, but not in normal controls. Other mammalian filtration systems also show a very low albumin sieving coefficient—for example, the choroid plexus in humans has a sieving coefficient of 0.003–0.0008. Finally, mutation of a podocyte-specific gene (NPHS2, which encodes podocin) is sufficient to result in nephrotic-range proteinuria.

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Acknowledgements

We apologize for not having cited all the excellent studies owing to limitations of space. M. J. Moeller is supported by a grant from TP17 SFB/Transregio 57 of the DFG, the European Research Projects on Rare Diseases Project Rare-G # 01 GM 1208A. M. J. Moeller is a member of the SFB/Transregio 57 DFG Mechanisms of Organ Fibrosis consortium.

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  1. Department of Nephrology and Clinical Immunology (Internal Medicine II), RWTH Aachen University Hospital, Pauwelsstrasse 30, D-52074, Aachen, Germany

    Marcus J. Moeller

  2. Department of Cellular and Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, 46202, IN, USA

    George A. Tanner

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Correspondence to Marcus J. Moeller.

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Moeller, M., Tanner, G. Podocytes are key—although albumin never reaches the slit diaphragm. Nat Rev Nephrol 10, 180 (2014). https://doi.org/10.1038/nrneph.2013.58-c2

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