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Bissinger, R.* ; Nemkov, T.* ; D Alessandro, A.* ; Grau, M.* ; Dietz, T.* ; Bohnert, B.N. ; Essigke, D.* ; Wörn, M.* ; Schaefer, L.* ; Xiao, M.* ; Beirne, J.M.* ; Kalo, M.Z.* ; Schork, A. ; Bakchoul, T.* ; Omage, K.* ; Kong, L.* ; González-Menéndez, I.* ; Quintanilla-Martinez, L.* ; Fehrenbacher, B.* ; Schaller, M.* ; Dhariwal, A.* ; Birkenfeld, A.L. ; Grahammer, F.* ; Qadri, S.M.* ; Artunc, F.

Proteinuric chronic kidney disease is associated with altered red blood cell lifespan, deformability and metabolism.

Kidney Int. 100, 1227-1239 (2021)
Postprint DOI PMC
Open Access Hybrid
Anemia is a common complication of chronic kidney disease, affecting the quality of life of patients. Among various factors, such as iron and erythropoietin deficiency, reduced red blood cell (RBC) lifespan has been implicated in the pathogenesis of anemia. However, mechanistic data on in vivo RBC dysfunction in kidney disease are lacking. Herein, we describe the development of chronic kidney disease-associated anemia in mice with proteinuric kidney disease resulting from either administration of doxorubicin or an inducible podocin deficiency. In both experimental models, anemia manifested at day 10 and progressed at day 30 despite increased circulating erythropoietin levels and erythropoiesis in the bone marrow and spleen. Circulating RBCs in both mouse models displayed altered morphology and diminished osmotic-sensitive deformability together with increased phosphatidylserine externalization on the outer plasma membrane, a hallmark of RBC death. Fluorescence-labelling of RBCs at day 20 of mice with doxorubicin-induced kidney disease revealed premature clearance from the circulation. Metabolomic analyses of RBCs from both mouse models demonstrated temporal changes in redox recycling pathways and Lands' cycle, a membrane lipid remodeling process. Anemic patients with proteinuric kidney disease had an increased proportion of circulating phosphatidylserine-positive RBCs. Thus, our observations suggest that reduced RBC lifespan, mediated by altered RBC metabolism, reduced RBC deformability, and enhanced cell death contribute to the development of anemia in proteinuric kidney disease.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Anemia ; Deformability ; Kidney Disease ; Lands’ Cycle ; Proteinuria ; Red Blood Cells ; Redox Recycling ; Cell Death ; Metabolism; Anemia; Carnitine; Acetylcarnitine; Erythropoietin; Transferrin; Stress; Health; Death; Serum
Language english
Publication Year 2021
HGF-reported in Year 2021
ISSN (print) / ISBN 0085-2538
e-ISSN 1523-1755
Journal Kidney International
Quellenangaben Volume: 100, Issue: 6, Pages: 1227-1239 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place Ste 800, 230 Park Ave, New York, Ny 10169 Usa
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)
POF-Topic(s) 90000 - German Center for Diabetes Research
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-502400-001
Grants Canadian Blood Services
Interdisziplinares Zentrum fur Klinische Forschung (IZKF) grant by the medical faculty of Tubingen University
German Research Foundation
DOI 10.1016/j.kint.2021.08.024
WOS ID WOS:000722435300017
Scopus ID 85118233211
PubMed ID 34537228
Erfassungsdatum 2021-10-15
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