The Study of Long Term Sequelae and the Risk Factors of Scar Formation, as Well as Host Susceptibility Genes and Related Adhesive Genes of Uropathogenic E. coli in Acute Lobar Nephronia in Children (II)

The clinical severity of acute renal bacterial infection spans continuously from an uncomplicated lower urinary-tract infection (UTI) to frank abscess formation. Among this suite of renal inflammatory diseases, acute lobar nephronia (ALN), also known as acute focal bacterial nephritis (AFBN), has been diagnosed with ever-increasing frequency in patients, due to the advancement of non-invasive imaging-technique modalities. ALN presents as a localized nonliquefactive inflammatory renal bacterial infection, which typically involves one or more lobes. It has previously been indicated as a complicated form of acute renal infection, representing the progression of the inflammatory process of acute pyelonephritis (APN). ALN may also represent a relatively early stage of the development of renal abscess. Differential diagnosis of these renal inflammatory diseases, however, is not easy due to the great similarity in clinical presentation and laboratory findings among these diseases. We have proposed a new imaging work-up scheme that utilizes a combination of ultrasonography (US) and computed tomography (CT) for ALN diagnosis. This scheme does not only improve the efficacy of CT performance but also the overall sensitivity of diagnosing ALN. With the utilization of this diagnosing scheme, we have lately conducted a prospective treatment efficacy comparison study for pediatric ALN patients with a three-week intravenous plus oral antimicrobial therapy regimen versus a two-week antibiotic therapy protocol that is commonly utilized for treating APN patients. Treatment failures were noted only in the 表 C011E 共 3 頁第 2 頁 two-week treatment group. Prolonged fever prior to admission, and positive Escherichia coli growth (＞105 cfu/mL) in urine culture were noted as risk factors for treatment failure. We also noted that Escherichia coli is the most common pathogen cultured in ALN and the proportion of Escherichia coli cultured is much greater than that reported for first-time UTIs. Moreover, neither any underlying disease nor any structure abnormalities in urinary-tract system other than VUR were noted in these ALN patients. Further analysis of the Escherichia coli isolates from the ALN patients revealed that diverse genotypes were found among the E. coli isolates. Among the pathogenetic determinants examined, multivariate logistic regression analysis indicated that a papG II allele was the only significant urovirulence factor associated with ALN (p＜0.005; odds ratio, 17.16). This association was independent of the presence of VUR. While no specific genetic lineage was identified among the E. coli isolates studied, a papG II gene was found to be strongly associated with the cause of ALN among pediatric patients. However, MDCK assay has implicated other gene that has yet been characterized may act synergistically with papG II to enhance uroepithelial cell adhesion capability of clinical isolates from APN. Henceforth, a unique Transposome insertion technique is proposed in this study to identify this potential gene conferring its cell adhesion capability. Moreover, several previous experimental studies have suggested that intact immune system is required for a functional defense against UTI. These findings implicated that, other than bacterial factors, host factors should also take roles in the pathogenesis of ALN. In addition, such roles may be different from those for the host factors in the less severe renal inflammatory disease, such as APN. Hence, in this study, we will explore the correlations among the host factors (i.e. through examining the mRNA and expression levels of the IL-8 receptors, CXCR1 and CXCR2, and Toll-like receptor, TLR4, as well as the SNPs of the gene regulating IL-8 receptors, CXCR1 and CXCR2, and TLR4) and the disease entities (ALN, APN and healthy controls). In addition, to characterize the long-term sequelae, such as renal scarring, of those patients affected with ALN, 99mTc DMSA renal SPECT follow-ups will be scheduled for those successfully managed by different antibiotic protocols. Through this study, in combined with our earlier results for the medical management of ALN patients as well as those for the urovirulent determinant analysis of the clinical E. coli isolates, a better understanding of pathogenesis of this severe pediatric bacterial renal inflammatory disease (i.e. ALN) can be achieved, and resulting in a better treatment outcome.

Project ID:PC9808-0774
External Project ID:NSC98-2314-B182-065-MY3