Alkali therapy protects renal function, suppresses inflammation, and improves cellular metabolism in kidney disease
Pastor Arroyo EM, Yassini N, Sakiri E, Russo G, Bourgeois S, Mohebbi N, Amann KU, Joller N, Wagner CA, Imenez Silva PH (2022)
Publication Type: Journal article
Publication year: 2022
Journal
Book Volume: 136
Pages Range: 557-577
Journal Issue: 8
DOI: 10.1042/CS20220095
Abstract
Chronic kidney disease (CKD) affects approximately 10-13% of the population worldwide and halting its progression is a major clinical challenge. Metabolic acidosis is both a consequence and a possible driver of CKD progression. Alkali therapy counteracts these effects in CKD patients, but underlying mechanisms remain incompletely understood. Here we show that bicarbonate supplementation protected renal function in a murine CKD model induced by an oxalate-rich diet. Alkali therapy had no effect on the aldosterone-endothelin axis but promoted levels of the anti-aging protein klotho; moreover, it suppressed adhesion molecules required for immune cell invasion along with reducing T-helper cell and inflammatory monocyte invasion. Comparing transcriptomes from the murine crystallopathy model and from human biopsies of kidney transplant recipients (KTRs) suffering from acidosis with or without alkali therapy unveils parallel transcriptome responses mainly associated with lipid metabolism and oxidoreductase activity. Our data reveal novel pathways associated with acidosis in kidney disease and sensitive to alkali therapy and identifies potential targets through which alkali therapy may act on CKD and that may be amenable for more targeted therapies.
Authors with CRIS profile
Involved external institutions
University of Zurich / Universität Zürich (UZH)
Switzerland (CH)
Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis (Kidney.CH)
Switzerland (CH)
Switzerland (CH)
Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis (Kidney.CH)
Switzerland (CH)
How to cite
APA:
Pastor Arroyo, E.M., Yassini, N., Sakiri, E., Russo, G., Bourgeois, S., Mohebbi, N.,... Imenez Silva, P.H. (2022). Alkali therapy protects renal function, suppresses inflammation, and improves cellular metabolism in kidney disease. Clinical Science, 136(8), 557-577. https://doi.org/10.1042/CS20220095
MLA:
Pastor Arroyo, Eva Maria, et al. "Alkali therapy protects renal function, suppresses inflammation, and improves cellular metabolism in kidney disease." Clinical Science 136.8 (2022): 557-577.
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