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A molecular mechanism explaining albuminuria in kidney disease

Butt, Linus (author)
Univ Cologne, Dept Internal Med 2, Fac Med, Cologne, Germany.;Univ Cologne, Ctr Mol Med Cologne, Fac Med, Cologne, Germany.;Univ Hosp Cologne, Cologne, Germany.
Jess, David Unnersjö (author)
KTH,Biofysik,Science for Life Laboratory, SciLifeLab,Univ Cologne, Dept Internal Med 2, Fac Med, Cologne, Germany.;Univ Cologne, Ctr Mol Med Cologne, Fac Med, Cologne, Germany.;Univ Hosp Cologne, Cologne, Germany.
Hohne, Martin (author)
Univ Cologne, Dept Internal Med 2, Fac Med, Cologne, Germany.;Univ Cologne, Ctr Mol Med Cologne, Fac Med, Cologne, Germany.;Univ Hosp Cologne, Cologne, Germany.
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Edwards, Aurelie (author)
Boston Univ, Dept Biomed Engn, Boston, MA USA.
Binz-Lotter, Julia (author)
Univ Cologne, Dept Internal Med 2, Fac Med, Cologne, Germany.;Univ Cologne, Ctr Mol Med Cologne, Fac Med, Cologne, Germany.;Univ Hosp Cologne, Cologne, Germany.
Reilly, Dervla (author)
Univ Cologne, Dept Internal Med 2, Fac Med, Cologne, Germany.;Univ Cologne, Ctr Mol Med Cologne, Fac Med, Cologne, Germany.;Univ Hosp Cologne, Cologne, Germany.
Hahnfeldt, Robert (author)
Univ Cologne, Dept Internal Med 2, Fac Med, Cologne, Germany.;Univ Cologne, Ctr Mol Med Cologne, Fac Med, Cologne, Germany.;Univ Hosp Cologne, Cologne, Germany.
Ziegler, Vera (author)
Univ Regensburg, Inst Physiol, Regensburg, Germany.
Fremter, Katharina (author)
Univ Regensburg, Inst Physiol, Regensburg, Germany.
Rinschen, Markus M. (author)
Univ Cologne, Dept Internal Med 2, Fac Med, Cologne, Germany.;Univ Cologne, Ctr Mol Med Cologne, Fac Med, Cologne, Germany.;Univ Hosp Cologne, Cologne, Germany.;Scripps Res Inst, Ctr Mass Spectrometry & Metabol, La Jolla, CA USA.
Helmstaedter, Martin (author)
Univ Freiburg, Dept Med 4, Fac Med, Med Ctr, Freiburg, Germany.;Univ Freiburg, Signalling Res Ctr BIOSS & CIBSS, Freiburg, Germany.
Ebert, Lena K. (author)
Univ Cologne, Dept Internal Med 2, Fac Med, Cologne, Germany.;Univ Cologne, Ctr Mol Med Cologne, Fac Med, Cologne, Germany.;Univ Hosp Cologne, Cologne, Germany.
Castrop, Hayo (author)
Univ Regensburg, Inst Physiol, Regensburg, Germany.
Hackl, Matthias J. (author)
Univ Cologne, Dept Internal Med 2, Fac Med, Cologne, Germany.;Univ Cologne, Ctr Mol Med Cologne, Fac Med, Cologne, Germany.;Univ Hosp Cologne, Cologne, Germany.
Walz, Gerd (author)
Univ Freiburg, Dept Med 4, Fac Med, Med Ctr, Freiburg, Germany.;Univ Freiburg, Signalling Res Ctr BIOSS & CIBSS, Freiburg, Germany.
Brinkkoetter, Paul T. (author)
Univ Cologne, Dept Internal Med 2, Fac Med, Cologne, Germany.;Univ Cologne, Ctr Mol Med Cologne, Fac Med, Cologne, Germany.;Univ Hosp Cologne, Cologne, Germany.
Liebau, Max C. (author)
Univ Cologne, Fac Med, Dept Pediat, Cologne, Germany.;Univ Cologne, Ctr Mol Med, Fac Med, Cologne, Germany.
Tory, Kalman (author)
Semmelweis Univ, Dept Pediat 1, MTA SE Lendulet Nephrogenet Lab, Budapest, Hungary.
Hoyer, Peter F. (author)
Univ Duisburg Essen, Univ Childrens Hosp, Clin Pediat 2, Essen, Germany.
Beck, Bodo B. (author)
Univ Cologne, Inst Human Genet, Fac Med, Cologne, Germany.
Brismar, Hjalmar (author)
Karolinska Institutet,KTH,Biofysik
Blom, Hans, 1968- (author)
KTH,Biofysik
Schermer, Bernhard (author)
Univ Cologne, Dept Internal Med 2, Fac Med, Cologne, Germany.;Univ Cologne, Ctr Mol Med Cologne, Fac Med, Cologne, Germany.;Univ Hosp Cologne, Cologne, Germany.;Univ Cologne, Fac Med, CECAD, Cologne, Germany.
Benzing, Thomas (author)
Univ Cologne, Dept Internal Med 2, Fac Med, Cologne, Germany.;Univ Cologne, Ctr Mol Med Cologne, Fac Med, Cologne, Germany.;Univ Hosp Cologne, Cologne, Germany.;Univ Cologne, Fac Med, CECAD, Cologne, Germany.
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Univ Cologne, Dept Internal Med 2, Fac Med, Cologne, Germany;Univ Cologne, Ctr Mol Med Cologne, Fac Med, Cologne, Germany.;Univ Hosp Cologne, Cologne, Germany. Biofysik (creator_code:org_t)
2020-05-11
2020
English.
In: Nature Metabolism. - : Springer Nature. - 2522-5812. ; 2:5, s. 461-474
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Mammalian kidneys constantly filter large amounts of liquid, with almost complete retention of albumin and other macromolecules in the plasma. Breakdown of the three-layered renal filtration barrier results in loss of albumin into urine (albuminuria) across the wall of small renal capillaries, and is a leading cause of chronic kidney disease. However, exactly how the renal filter works and why its permeability is altered in kidney diseases is poorly understood. Here we show that the permeability of the renal filter is modulated through compression of the capillary wall. We collect morphometric data prior to and after onset of albuminuria in a mouse model equivalent to a human genetic disease affecting the renal filtration barrier. Combining quantitative analyses with mathematical modelling, we demonstrate that morphological alterations of the glomerular filtration barrier lead to reduced compressive forces that counteract filtration pressure, thereby resulting in capillary dilatation, and ultimately albuminuria. Our results reveal distinct functions of the different layers of the filtration barrier and expand the molecular understanding of defective renal filtration in chronic kidney disease.

Subject headings

NATURVETENSKAP  -- Biologi -- Biofysik (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Biophysics (hsv//eng)

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art (subject category)

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