Makoto Mizutani1, Shunji Hasegawa2, Takeshi Matsushige1, Naoki Ohta1, Setsuaki Kittaka1, Madoka Hoshide1, Takeshi Kusuda1, Kazumasa Takahashi1, Kiyoshi Ichihara3, Shouichi Ohga4. 1. Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan. 2. Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan. Electronic address: shunji@yamaguchi-u.ac.jp. 3. Department of Clinical Laboratory Sciences, Faculty of Health Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan. 4. Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Abstract
BACKGROUND: Acute focal bacterial nephritis (AFBN) is a severe form of upper urinary tract infection (UTI) with neurological manifestations and focal renal mass lesions on computed tomography (CT). Prolonged antibiotic therapy may improve the renal outcome, but the early differential diagnosis of AFBN from acute pyelonephritis (APN) is challenging. We searched for effective biomarkers of AFBN based on the pathophysiology of upper UTIs. METHODS: Of 52 upper UTI cases treated at Yamaguchi University between 2009 and 2016, 38 pediatric patients with AFBN (n=17) or APN (n=21) who underwent ultrasonography and/or CT were enrolled. The clinical data and serum cytokine concentrations were analyzed to differentiate AFBN from APN. RESULTS: AFBN patients tended to be older, and have a higher body temperature, longer febrile period, more frequent neurological symptoms, higher immature neutrophil count, lower lymphocyte count, higher procalcitonin and urine β2-microglobulin levels. AFBN patients showed higher serum levels of IFN-γ, IL-6, IL-10 and soluble TNF-receptor 1 (sTNFR1) (all p<0.05). Although the cytokine levels were variably correlated among each other, multiple logistic regression analysis revealed that combination of IFN-γ and IL-6 levels were most relevant for distinguishing AFBN from APN. The discriminant power of the logistic equation was 0.86 in terms of the area under the curve by the ROC analysis. CONCLUSIONS: Circulating 4 out of 7 cytokines in AFBN patients were at higher levels compared with those in APN patients. IFN-γ and IL-6 levels might most effectively distinguish AFBN from APN.
BACKGROUND: Acute focal bacterial nephritis (AFBN) is a severe form of upper urinary tract infection (UTI) with neurological manifestations and focal renal mass lesions on computed tomography (CT). Prolonged antibiotic therapy may improve the renal outcome, but the early differential diagnosis of AFBN from acute pyelonephritis (APN) is challenging. We searched for effective biomarkers of AFBN based on the pathophysiology of upper UTIs. METHODS: Of 52 upper UTI cases treated at Yamaguchi University between 2009 and 2016, 38 pediatric patients with AFBN (n=17) or APN (n=21) who underwent ultrasonography and/or CT were enrolled. The clinical data and serum cytokine concentrations were analyzed to differentiate AFBN from APN. RESULTS:AFBNpatients tended to be older, and have a higher body temperature, longer febrile period, more frequent neurological symptoms, higher immature neutrophil count, lower lymphocyte count, higher procalcitonin and urine β2-microglobulin levels. AFBNpatients showed higher serum levels of IFN-γ, IL-6, IL-10 and soluble TNF-receptor 1 (sTNFR1) (all p<0.05). Although the cytokine levels were variably correlated among each other, multiple logistic regression analysis revealed that combination of IFN-γ and IL-6 levels were most relevant for distinguishing AFBN from APN. The discriminant power of the logistic equation was 0.86 in terms of the area under the curve by the ROC analysis. CONCLUSIONS: Circulating 4 out of 7 cytokines in AFBNpatients were at higher levels compared with those in APN patients. IFN-γ and IL-6 levels might most effectively distinguish AFBN from APN.
Authors: Nader Shaikh; Judith M Martin; Alejandro Hoberman; Megan Skae; Linette Milkovich; Andrew Nowalk; Christi McElheny; Robert W Hickey; Diana Kearney; Massoud Majd; Eglal Shalaby-Rana; George Tseng; John F Alcorn; Jay Kolls; Marcia Kurs-Lasky; Zhiguang Huo; William Horne; Greg Lockhart; Hans Pohl; Timothy R Shope Journal: J Pediatr Date: 2019-03-21 Impact factor: 4.406