The Role of Cytokines in Urinary Tract Infection and Renal Scarring in Children

• Main Authors: Ji-Nan, 許績男
• Other Authors: 呂克桓
• Format: Others
• Language: en_US
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/50063959502607986321

博士 === 中山醫學大學 === 醫學研究所 === 95 === Backgrounds and Objectives: Urinary tract infection (UTI) is a common clinical disorder in younger infants and children. The cumulative incidence of UTIs has been reported to be 2-8% by 10 years of age. Isotope uptake studies with 99mTc-dimercaptosuccinic acid (DMSA) scan have shown that the renal parenchyma is affected in about 55-75% of children with febrile UTI. Approximately 10-65% of these children may result in permanent renal damage and renal scarring after the infection. Further, renal scarring later in life may lead to the development of subsequent hypertension, proteinuria and renal insufficiency that is one of the major causes of end-stage renal disease in many countries. The inflammatory cytokines interleukin (IL)-1β, IL-6 and IL-8 play an important role in response to bacterial infection and the progression of renal inflammation. However, there have been relatively few studies of the role of these cytokines in children with acute pyelonephritis and subsequent renal scarring. The aims of this prospective study were to investigate the IL-1β, IL-6 and IL-8 responses in children with first-time acute pyelonephritis confirmed by DMSA scan, and also to evaluate the relationships of cytokines with other inflammatory markers, vesicoureteral reflux as well as renal scarring. Methods: The protocol was designed into two parts according to the variety of cytokines: 1) A total of 78 children aged 1 month to 10 years with a diagnosis of first-time febrile UTI were included. The following inflammatory markers were assessed: fever; white blood cells (WBC) count; C-reactive protein (CRP); as well as serum and urine IL-6 and IL-8. Serum and urine samples were collected for IL-6 and IL-8 measurements by enzyme-linked immunosorbent assay (ELISA) before and after antibiotic treatment of the infection. All children underwent renal ultrasound examination and DMSA scan for detection of anomalies of the urinary tract and the presence of pyelonephritic lesions within the first 1 week of hospitalization. The patients were divided into the acute pyelonephritis group (n = 42) and the lower UTI group (n = 36) according to the results of DMSA scans. We also collected 20 children with other febrile illnesses and 12 healthy children with age- and sex-matched served as conntrols. Follow-up DMSA scans were performed again at 6-12 months after the initial infection to detect renal scarring. 2)A total of 75 children aged 1-121 months with a diagnosis of first-time febrile UTI were studied. The following inflammatory markers were assessed: fever; CRP; WBC count; neutrophil count; and urine IL-1β. Urine samples were collected for IL-1β measurement by ELISA before and after antibiotic treatment of the infection. The 75 children were divided into acute pyelonephritis (n = 41) and lower UTI (n = 34) groups according to the findings of DMSA scans. Follow-up DMSA scan was performed at 6-12 months after the acute pyelonephritis to detect renal scarring. Twenty children with other febrile illnesses served as non-renal febrile controls. Results: 1) Serum and urine IL-6 and IL-8 studies: Fever, WBC count and CRP levels were significantly higher in children with acute pyelonephritis than in those with lower UTI (all P <0.001). There were significant differences in the initial serum and urine levels of IL-6 and IL-8 among the children with acute pyelonephritis and lower UTI and non-renal febrile controls and healthy controls (all P <0.001). Compared to post treatment, the initial serum and urine IL-6 and IL-8 levels were significantly higher for both the acute pyelonephritis (P <0.001) and lower UTI groups (P <0.001). Renal scarring was detected at the follow-up DMSA scans in 12 (30.8%) of the 39 children with follow-up DMSA scans. Both serum and urine IL-6 levels during the acute phase of pyelonephritis were significantly higher in the children with renal scarring than in those without (P <0.05 and P <0.01, respectively). The mean age of children with renal scarring was significantly lower compared to those without (P <0.05). 2) Urine IL-1β study: Fever, WBC count, neutrophil count and CRP were significantly higher in the children with acute pyelonephritis than in those with lower UTI (all P <0.001). The initial urine IL-1β levels of children with acute pyelonephritis were significantly higher when compared with lower UTI and non-renal febrile controls (P <0.001). The children with acute pyelonephritis had significantly higher initial urine IL-1β levels than after appropriate antibiotic treatment (P <0.001). Urine IL-1β in children with acute pyelonephritis was positively correlated with fever, CRP, WBC, neutrophil and leucocyturia. Renal scarring wasfound in 12 (29.3%) of the 41 children with acute pyelonephritis. Initial urine IL-1β levels were significantly lower in children with renal scarring than in those without renal scarring (P <0.01). Conclusions: These results demonstrate that systemic inflammatory markers (fever, CRP, WBC count and neutrophil count) were significantly higher in children with acute pyelonephritis than in those with lower UTI. Serum or urine IL-1β, IL-6 and IL-8 levels are useful diagnostic markers for early recognition of acute pyelonephritis in febrile children. Furthermore, our findings demonstrate that in young children with first-time acute pyelonephritis, elevations of the acute-phase serum and urine IL-6 levels were correlated with the development of subsequent renal scarring. Our results also indicate that acute urine IL-1β level might be used as a predictor of later renal scarring.