Butt, Linus and Unnersjoe-Jess, David and Hohne, Martin and Edwards, Aurelie and Binz-Lotter, Julia and Reilly, Dervla and Hahnfeldt, Robert and Ziegler, Vera and Fremter, Katharina and Rinschen, Markus M. and Helmstaedter, Martin and Ebert, Lena K. and Castrop, Hayo and Hackl, Matthias J. and Walz, Gerd and Brinkkoetter, Paul T. and Liebau, Max C. and Tory, Kalman and Hoyer, Peter F. and Beck, Bodo B. and Brismar, Hjalmar and Blom, Hans and Schermer, Bernhard and Benzing, Thomas (2020) A molecular mechanism explaining albuminuria in kidney disease. NATURE METABOLISM, 2 (5). 461-+. ISSN , 2522-5812
Full text not available from this repository. (Request a copy)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: | Article |
|---|---|
| Uncontrolled Keywords: | GLOMERULAR-BASEMENT-MEMBRANE; SLIT DIAPHRAGM; PODOCYTE DEPLETION; FILTRATION BARRIER; NEPHROTIC SYNDROME; ANALYSIS REVEALS; PROXIMAL TUBULE; CAPILLARY WALL; MUTATIONS; PROTEINS; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Wolf Hayo Castrop |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Mar 2021 12:53 |
| Last Modified: | 24 Mar 2021 12:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44646 |
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