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The pathogenesis and prognostic significance of BWF and AKI are not well understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A prospective observational cohort study was conducted to evaluate the association between BWF and AKI in children hospitalized with an acute febrile illness. Secondary objectives were to examine the association of AKI and BWF with (i) host response biomarkers and (ii) mortality. AKI was defined using the Kidney Disease: Improving Global Outcomes criteria and BWF was based on parental report of tea-colored urine. Host markers of immune and endothelial activation were quantified on admission plasma samples. The relationships between BWF and AKI and clinical and biologic factors were evaluated using multivariable regression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We evaluated BWF and AKI in 999 children with acute febrile illness (mean age 1.7\u00a0years (standard deviation 1.06), 55.7% male). At enrollment, 8.2% of children had a history of BWF, 49.5% had AKI, and 11.1% had severe AKI. A history of BWF was independently associated with 2.18-fold increased odds of AKI (95% CI 1.15 to 4.16). When examining host response, severe AKI was associated with increased immune and endothelial activation (increased CHI3L1, sTNFR1, sTREM-1, IL-8, Angpt-2, sFlt-1) while BWF was predominantly associated with endothelial activation (increased Angpt-2 and sFlt-1, decreased Angpt-1). The presence of severe AKI, not BWF, was associated with increased risk of in-hospital death (RR, 2.17 95% CI 1.01 to 4.64) adjusting for age, sex, and disease severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>BWF is associated with severe AKI in children hospitalized with a severe febrile illness. Increased awareness of AKI in the setting of BWF, and improved access to AKI diagnostics, is needed to reduce disease progression and in-hospital mortality in this high-risk group of children through early implementation of kidney-protective measures.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12916-022-02410-4","type":"journal-article","created":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:03:03Z","timestamp":1656633783000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Blackwater fever and acute kidney injury in children hospitalized with an acute febrile illness: pathophysiology and prognostic significance"],"prefix":"10.1186","volume":"20","author":[{"given":"Andrea L.","family":"Conroy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Hawkes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Leligdowicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Mufumba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle C.","family":"Starr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Namasopo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandy C.","family":"John","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert O.","family":"Opoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin C.","family":"Kain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,1]]},"reference":[{"issue":"3","key":"2410_CR1","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/ki.2013.153","volume":"84","author":"AJP Lewington","year":"2013","unstructured":"Lewington AJP, Cerd\u00e1 J, Mehta RL. 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This study was approved by Makerere University School of Medicine Research Ethics Board (SOMREC, REC Protocol # REF 2011\u2013255), the Uganda National Council for Science and Technology (UNCST), and the University Health Network Research Ethics Board (UHN-REB, REB number 12\u20130039-AE) and was registered on clinicaltrials.gov (identifier: NCT04726826).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"KCK and ALC are inventors on a patent related to host biomarkers for early determination of critical or life-threatening response to illness and\/or treatment response. Dr. Chandy John is a member of the editorial board of BMC Medicine. All other authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"221"}}