Alkali therapy protects renal function, suppresses inflammation, and improves cellular metabolism in kidney disease
| Autor: | 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 |
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| Přispěvatelé: | University of Zurich |
| Rok vydání: | 2022 |
| Předmět: |
Inflammation
Male 610 Medicine & health 10071 Functional Genomics Center Zurich 2700 General Medicine General Medicine Alkalies 10263 Institute of Experimental Immunology Kidney 10052 Institute of Physiology Mice Animals Humans 10035 Clinic for Nephrology 10239 Institute of Laboratory Animal Science Female Renal Insufficiency Chronic Acidosis 11493 Department of Quantitative Biomedicine |
| DOI: | 10.5167/uzh-218512 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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