Department of Pediatrics, Indiana University School of Medicine, 1044 West Walnut St., Building 4, Indianapolis, IN, 46202, USA.
Division of Pediatric Infectious Diseases, 3-593 Edmonton Clinic Health Academy, University of Alberta, Edmonton, AB, T6G1C9, Canada.
BMC Med. 2022 Jul 1;20(1):221. doi: 10.1186/s12916-022-02410-4.
Acute kidney injury (AKI) and blackwater fever (BWF) are related but distinct renal complications of acute febrile illness in East Africa. The pathogenesis and prognostic significance of BWF and AKI are not well understood.
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.
We evaluated BWF and AKI in 999 children with acute febrile illness (mean age 1.7 years (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.
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.
急性肾损伤（AKI）和黑水热（BWF）是东非急性发热性疾病相关但不同的肾脏并发症。BWF 和 AKI 的发病机制和预后意义尚不清楚。
进行了一项前瞻性观察队列研究，以评估 BWF 和 AKI 在因急性发热性疾病住院的儿童中的关联。次要目标是检查 AKI 和 BWF 与（i）宿主反应生物标志物和（ii）死亡率的关联。使用肾脏疾病：改善全球结果标准定义 AKI，根据父母报告茶色尿定义 BWF。入院时量化血浆样本中免疫和内皮激活的宿主标志物。使用多变量回归评估 BWF 和 AKI 与临床和生物学因素之间的关系。
我们评估了 999 名急性发热性疾病患儿的 BWF 和 AKI（平均年龄 1.7 岁（标准差 1.06），55.7%为男性）。入组时，8.2%的儿童有 BWF 病史，49.5%有 AKI，11.1%有严重 AKI。BWF 病史与 AKI 的几率增加 2.18 倍独立相关（95%CI 1.15 至 4.16）。在检查宿主反应时，严重 AKI 与免疫和内皮激活增加相关（CHI3L1、sTNFR1、sTREM-1、IL-8、Angpt-2、sFlt-1 增加），而 BWF 主要与内皮激活相关（Angpt-2 和 sFlt-1 增加，Angpt-1 减少）。严重 AKI 的存在，而不是 BWF，与住院期间死亡风险增加相关（调整年龄、性别和疾病严重程度后的 RR，2.17 95%CI 1.01 至 4.64）。
BWF 与儿童因严重发热性疾病住院时的严重 AKI 相关。在 BWF 存在的情况下，需要提高对 AKI 的认识，并改善 AKI 诊断的可及性，通过早期实施肾脏保护措施，减少该高危人群的疾病进展和住院死亡率。
