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A molecular mechanism explaining albuminuria in kidney disease

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A molecular mechanism explaining albuminuria in kidney disease. / Butt, Linus; Unnersjö-Jess, David; Höhne, Martin; Edwards, Aurelie; Binz-Lotter, Julia; Reilly, Dervla; Hahnfeldt, Robert; Ziegler, Vera; Fremter, Katharina; Rinschen, Markus M; Helmstädter, Martin; Ebert, Lena K; Castrop, Hayo; Hackl, Matthias J; Walz, Gerd; Brinkkoetter, Paul T; Liebau, Max C; Tory, Kálmán; Hoyer, Peter F; Beck, Bodo B; Brismar, Hjalmar; Blom, Hans; Schermer, Bernhard; Benzing, Thomas.

In: NAT METAB, Vol. 2, No. 5, 05.2020, p. 461-474.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Butt, L, Unnersjö-Jess, D, Höhne, M, Edwards, A, Binz-Lotter, J, Reilly, D, Hahnfeldt, R, Ziegler, V, Fremter, K, Rinschen, MM, Helmstädter, M, Ebert, LK, Castrop, H, Hackl, MJ, Walz, G, Brinkkoetter, PT, Liebau, MC, Tory, K, Hoyer, PF, Beck, BB, Brismar, H, Blom, H, Schermer, B & Benzing, T 2020, 'A molecular mechanism explaining albuminuria in kidney disease', NAT METAB, vol. 2, no. 5, pp. 461-474. https://doi.org/10.1038/s42255-020-0204-y

APA

Butt, L., Unnersjö-Jess, D., Höhne, M., Edwards, A., Binz-Lotter, J., Reilly, D., Hahnfeldt, R., Ziegler, V., Fremter, K., Rinschen, M. M., Helmstädter, M., Ebert, L. K., Castrop, H., Hackl, M. J., Walz, G., Brinkkoetter, P. T., Liebau, M. C., Tory, K., Hoyer, P. F., ... Benzing, T. (2020). A molecular mechanism explaining albuminuria in kidney disease. NAT METAB, 2(5), 461-474. https://doi.org/10.1038/s42255-020-0204-y

Vancouver

Butt L, Unnersjö-Jess D, Höhne M, Edwards A, Binz-Lotter J, Reilly D et al. A molecular mechanism explaining albuminuria in kidney disease. NAT METAB. 2020 May;2(5):461-474. https://doi.org/10.1038/s42255-020-0204-y

Bibtex

@article{ca0dc363867848c28bd03e99c8d2096d,
title = "A molecular mechanism explaining albuminuria in kidney disease",
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.",
keywords = "Albuminuria/etiology, Animals, Capillaries, Disease Models, Animal, Female, Genotype, Glomerular Filtration Barrier, Glomerular Filtration Rate, Humans, Kidney Glomerulus/pathology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Models, Theoretical, Podocytes/pathology, RNA/genetics, Renal Insufficiency, Chronic/complications, Vasodilation",
author = "Linus Butt and David Unnersj{\"o}-Jess and Martin H{\"o}hne and Aurelie Edwards and Julia Binz-Lotter and Dervla Reilly and Robert Hahnfeldt and Vera Ziegler and Katharina Fremter and Rinschen, {Markus M} and Martin Helmst{\"a}dter and Ebert, {Lena K} and Hayo Castrop and Hackl, {Matthias J} and Gerd Walz and Brinkkoetter, {Paul T} and Liebau, {Max C} and K{\'a}lm{\'a}n Tory and Hoyer, {Peter F} and Beck, {Bodo B} and Hjalmar Brismar and Hans Blom and Bernhard Schermer and Thomas Benzing",
year = "2020",
month = may,
doi = "10.1038/s42255-020-0204-y",
language = "English",
volume = "2",
pages = "461--474",
journal = "NAT METAB",
issn = "2522-5812",
publisher = "Springer",
number = "5",

}

RIS

TY - JOUR

T1 - A molecular mechanism explaining albuminuria in kidney disease

AU - Butt, Linus

AU - Unnersjö-Jess, David

AU - Höhne, Martin

AU - Edwards, Aurelie

AU - Binz-Lotter, Julia

AU - Reilly, Dervla

AU - Hahnfeldt, Robert

AU - Ziegler, Vera

AU - Fremter, Katharina

AU - Rinschen, Markus M

AU - Helmstädter, Martin

AU - Ebert, Lena K

AU - Castrop, Hayo

AU - Hackl, Matthias J

AU - Walz, Gerd

AU - Brinkkoetter, Paul T

AU - Liebau, Max C

AU - Tory, Kálmán

AU - Hoyer, Peter F

AU - Beck, Bodo B

AU - Brismar, Hjalmar

AU - Blom, Hans

AU - Schermer, Bernhard

AU - Benzing, Thomas

PY - 2020/5

Y1 - 2020/5

N2 - 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.

AB - 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.

KW - Albuminuria/etiology

KW - Animals

KW - Capillaries

KW - Disease Models, Animal

KW - Female

KW - Genotype

KW - Glomerular Filtration Barrier

KW - Glomerular Filtration Rate

KW - Humans

KW - Kidney Glomerulus/pathology

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Models, Theoretical

KW - Podocytes/pathology

KW - RNA/genetics

KW - Renal Insufficiency, Chronic/complications

KW - Vasodilation

U2 - 10.1038/s42255-020-0204-y

DO - 10.1038/s42255-020-0204-y

M3 - SCORING: Journal article

C2 - 32694662

VL - 2

SP - 461

EP - 474

JO - NAT METAB

JF - NAT METAB

SN - 2522-5812

IS - 5

ER -