{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T22:01:47Z","timestamp":1779919307077,"version":"3.53.1"},"reference-count":67,"publisher":"Portland Press Ltd.","issue":"8","license":[{"start":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T00:00:00Z","timestamp":1649289600000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,4,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Chronic kidney disease (CKD) affects approximately 10\u201313% 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\u2013endothelin 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.<\/jats:p>","DOI":"10.1042\/cs20220095","type":"journal-article","created":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T14:38:03Z","timestamp":1649342283000},"page":"557-577","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Alkali therapy protects renal function, suppresses inflammation, and improves cellular metabolism in kidney disease"],"prefix":"10.1042","volume":"136","author":[{"given":"Eva\u00a0Maria","family":"Pastor Arroyo","sequence":"first","affiliation":[{"name":"Institute of Physiology, University of Zurich, Zurich, Switzerland"},{"name":"National Center of Competence in Research, NCCR Kidney.CH, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nima","family":"Yassini","sequence":"additional","affiliation":[{"name":"Institute of Physiology, University of Zurich, Zurich, Switzerland"},{"name":"Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elif","family":"Sakiri","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo","family":"Russo","sequence":"additional","affiliation":[{"name":"Functional Genomics Center Z\u00fcrich, University of Z\u00fcrich and ETH Zurich, Zurich, Switzerland"},{"name":"EMBL Partner Institute for Genome, Editing Life Science Center, Vilnius University, Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soline","family":"Bourgeois","sequence":"additional","affiliation":[{"name":"Institute of Physiology, University of Zurich, Zurich, Switzerland"},{"name":"National Center of Competence in Research, NCCR Kidney.CH, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilufar","family":"Mohebbi","sequence":"additional","affiliation":[{"name":"National Center of Competence in Research, NCCR Kidney.CH, Switzerland"},{"name":"Division of Nephrology, University Hospital Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Amann","sequence":"additional","affiliation":[{"name":"Department of Nephropathology, Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Joller","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten\u00a0A.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Institute of Physiology, University of Zurich, Zurich, Switzerland"},{"name":"National Center of Competence in Research, NCCR Kidney.CH, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2805-3601","authenticated-orcid":false,"given":"Pedro\u00a0Henrique","family":"Imenez Silva","sequence":"additional","affiliation":[{"name":"Institute of Physiology, University of Zurich, Zurich, Switzerland"},{"name":"National Center of Competence in Research, NCCR Kidney.CH, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2022,4,21]]},"reference":[{"key":"2022042110155226400_B1","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/S0140-6736(17)30788-2","article-title":"Global kidney health 2017 and beyond: a roadmap for closing gaps in care, research, and policy","volume":"390","author":"Levin","year":"2017","journal-title":"Lancet North Am. 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