Alkali therapy protects renal function, suppresses inflammation, and improves cellular metabolism in kidney disease

Eva Maria Pastor Arroyo, Nima Yassini, Elif Sakiri, Giancarlo Russo, Soline Bourgeois, Nilufar Mohebbi, Kerstin Amann, Nicole Joller, Carsten A. Wagner, Pedro Henrique Imenez Silva*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)557-577
Number of pages21
JournalClinical Science
Volume136
Issue number8
DOIs
Publication statusPublished - Apr 2022
Externally publishedYes

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© 2022 The Author(s).

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