The effects of urine alkalinization on kidney function in critically ill patients with COVID-19: a proof-of-concept randomized clinical trial

DOI record: { "DOI": "10.1186/s40635-025-00739-7", "ISSN": [ "2197-425X" ], "URL": "http://dx.doi.org/10.1186/s40635-025-00739-7", "abstract": "<jats:title>Abstract</jats:title>\n <jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>Acute kidney injury (AKI) is a common complication of COVID-19. While the exact mechanisms remain unclear, direct viral infection of renal tubular epithelial cells is hypothesized. Given the pH-dependent entry of coronaviruses into host cells, urine alkalinization was proposed as a potential preventive strategy.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>This was a proof-of-concept prospective, randomized clinical trial in critically ill patients with COVID-19. Patients were randomized to urine alkalinization versus usual care. The intervention group received intravenous 8.4% sodium bicarbonate to achieve a urine pH ≥ 7.5 up to 10 days after randomization. The primary outcome was the proportion of patients achieving target urine pH. Secondary outcomes included changes in urine tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), AKI development, renal replacement therapy, and adverse effects.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>The trial was terminated early due to slow recruitment and the end of the COVID-19 pandemic. Sixteen patients were enrolled (median age 48 years old, 75% male). More patients in the intervention group achieved target urine pH than in the control group (75% vs 37.5%, <jats:italic>P</jats:italic> = 0.315). There was a separation of urine pH between both groups throughout 10 days (<jats:italic>P</jats:italic> = 0.097 for interaction). However, the intervention did not significantly impact urine [TIMP-2]x[IGFBP7] concentrations (<jats:italic>P</jats:italic> = 0.813 for interaction) or clinical outcomes, including AKI occurrence (risk ratio 0.6 (95% confidence interval 0.21, 1.70), <jats:italic>P</jats:italic> = 0.619). More patients in the intervention group experienced hypernatremia and metabolic alkalosis. Notably, patients with elevated urine [TIMP-2]x[IGFBP7] concentrations and AKI had higher ICU and 60-day mortality.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Conclusions</jats:title>\n <jats:p>While urine alkalinization is feasible and can increase urine pH, we could not demonstrate differences in AKI rates or changes in urine [TIMP-2]x[IGFBP7] concentrations in critically ill COVID-19 patients.</jats:p>\n </jats:sec>", "alternative-id": [ "739" ], "article-number": "33", "assertion": [ { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Received", "name": "received", "order": 1, "value": "16 December 2024" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Accepted", "name": "accepted", "order": 2, "value": "23 February 2025" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "First Online", "name": "first_online", "order": 3, "value": "7 March 2025" }, { "group": { "label": "Declarations", "name": "EthicsHeading" }, "name": "Ethics", "order": 1 }, { "group": { "label": "Ethics approval and consent to participate", "name": "EthicsHeading" }, "name": "Ethics", "order": 2, "value": "The study was approved by a National Research Ethics Committee in the UK (London—Harrow) (REC reference 21/HRA/0440) and carried out in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki). Written informed consent was obtained from participants or provided by a personal or professional consultee if the patient did not have capacity to consent for themselves. In a case where a consultee had given permission for the patient to take part, the patient was invited to give informed consent to continue participation or to withdraw from further participation as soon as they regained capacity." }, { "group": { "label": "Consent for publication", "name": "EthicsHeading" }, "name": "Ethics", "order": 3, "value": "Written consent for publication was obtained from participants or provided by a personal or professional consultee if the patient did not have capacity to consent for themselves. In a case where a consultee gave permission for the patient to take part, the patient was informed and invited to give informed consent for publication as soon as they regained capacity." }, { "group": { "label": "Competing interests", "name": "EthicsHeading" }, "name": "Ethics", "order": 4, "value": "MO has received research funding from Baxter and Biomerieux. The funding was paid to the institution. JAK discloses consulting fees from BioMérieux, AstraZeneca, Bayer, Novartis, Mitsubishi Tenabe, and Chugai Pharma; and employment and stock with Spectral Medical. NL, JPT, MM, and SS declare no conflict of interest." } ], "author": [ { "affiliation": [], "family": "Lumlertgul", "given": "Nuttha", "sequence": "first" }, { "affiliation": [], "family": "Kellum", "given": "John A.", "sequence": "additional" }, { "affiliation": [], "family": "Powell-Tuck", "given": "Jonah", "sequence": "additional" }, { "affiliation": [], "family": "Mathew", "given": "Moncy", "sequence": "additional" }, { "affiliation": [], "family": "Sardiwal", "given": "Sunita", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0001-9500-9080", "affiliation": [], "authenticated-orcid": false, "family": "Ostermann", "given": "Marlies", "sequence": "additional" } ], "container-title": "Intensive Care Medicine Experimental", "container-title-short": "ICMx", "content-domain": { "crossmark-restriction": false, "domain": [ "link.springer.com" ] }, "created": { "date-parts": [ [ 2025, 3, 7 ] ], "date-time": "2025-03-07T16:33:31Z", "timestamp": 1741365211000 }, "deposited": { "date-parts": [ [ 2025, 3, 7 ] ], "date-time": "2025-03-07T16:33:35Z", "timestamp": 1741365215000 }, "funder": [ { "name": "Baxter Global" } ], "indexed": { "date-parts": [ [ 2025, 3, 7 ] ], "date-time": "2025-03-07T17:10:20Z", "timestamp": 1741367420314, "version": "3.38.0" }, "is-referenced-by-count": 0, "issue": "1", "issued": { "date-parts": [ [ 2025, 3, 7 ] ] }, "journal-issue": { "issue": "1", "published-online": { "date-parts": [ [ 2025, 12 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2025, 3, 7 ] ], "date-time": "2025-03-07T00:00:00Z", "timestamp": 1741305600000 } }, { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2025, 3, 7 ] ], "date-time": "2025-03-07T00:00:00Z", "timestamp": 1741305600000 } } ], "link": [ { "URL": "https://link.springer.com/content/pdf/10.1186/s40635-025-00739-7.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/article/10.1186/s40635-025-00739-7/fulltext.html", "content-type": "text/html", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/content/pdf/10.1186/s40635-025-00739-7.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "297", "original-title": [], "prefix": "10.1186", "published": { "date-parts": [ [ 2025, 3, 7 ] ] }, "published-online": { "date-parts": [ [ 2025, 3, 7 ] ] }, "publisher": "Springer Science and Business Media LLC", "reference": [ { "DOI": "10.1093/ndt/gfab303", "author": "MK Sullivan", "doi-asserted-by": "publisher", "first-page": "271", "issue": "2", "journal-title": "Nephrol Dial Transplant", "key": "739_CR1", "unstructured": "Sullivan MK, Lees JS, Drake TM, Docherty AB, Oates G, Hardwick HE, Russell CD, Merson L, Dunning J, Nguyen-Van-Tam JS et al (2022) Acute kidney injury in patients hospitalized with COVID-19 from the ISARIC WHO CCP-UK Study: a prospective, multicentre cohort study. 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