Butt, Linus, Unnersjoe-Jess, David, Hohne, Martin, Edwards, Aurelie, Binz-Lotter, Julia, Reilly, Dervla, Hahnfeldt, Robert, Ziegler, Vera, Fremter, Katharina, Rinschen, Markus M., Helmstaedter, Martin, Ebert, Lena K., Castrop, Hayo, Hackl, Matthias J., Walz, Gerd, Brinkkoetter, Paul T., Liebau, Max C., Tory, Kalman, Hoyer, Peter F., Beck, Bodo B., Brismar, Hjalmar, Blom, Hans, Schermer, Bernhard and Benzing, Thomas (2020). A molecular mechanism explaining albuminuria in kidney disease. Nat. Metab., 2 (5). S. 461 - 484. BERLIN: NATURE RESEARCH. ISSN 2522-5812

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Butt, LinusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Unnersjoe-Jess, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hohne, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Edwards, AurelieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Binz-Lotter, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reilly, DervlaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hahnfeldt, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ziegler, VeraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fremter, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rinschen, Markus M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Helmstaedter, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ebert, Lena K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Castrop, HayoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hackl, Matthias J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Walz, GerdUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brinkkoetter, Paul T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liebau, Max C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tory, KalmanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoyer, Peter F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beck, Bodo B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brismar, HjalmarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blom, HansUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schermer, BernhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benzing, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-335228
DOI: 10.1038/s42255-020-0204-y
Journal or Publication Title: Nat. Metab.
Volume: 2
Number: 5
Page Range: S. 461 - 484
Date: 2020
Publisher: NATURE RESEARCH
Place of Publication: BERLIN
ISSN: 2522-5812
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GLOMERULAR-BASEMENT-MEMBRANE; SLIT DIAPHRAGM; PODOCYTE DEPLETION; FILTRATION BARRIER; NEPHROTIC SYNDROME; ANALYSIS REVEALS; PROXIMAL TUBULE; CAPILLARY WALL; MUTATIONS; PROTEINSMultiple languages
Endocrinology & MetabolismMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/33522

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