Urinary Measurement of Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 Helps Diagnose Acute Pyelonephritis in a Preclinical Model

Background. The study assessed whether measurement of urinary biomarkers of acute kidney injury could be helpful in diagnosing acute pyelonephritis and subsequent scarring. Method. Escherichia coli J96 (0.3？mL inoculum containing /mL) was directly injected into the renal cortex of 3-week-old female Sprague Dawley rats ( ), with saline substituted in a control group ( ). Following the injection, urine was collected 2, 7, 14, 28, and 42 days after injection. Urinary neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (Kim-1), and interleukin-18 were quantitatively measured using enzyme-linked immunosorbent assay (ELISA). The levels of the biomarkers were adjusted for creatinine. Time course changes within a group or between the groups were compared. Correlation analysis was performed to understand the relationship between urinary levels and histological scarring. Results. Significantly elevated urinary NGAL was evident at two and seven days after injection, and Kim-1 was elevated at two days after injection. Receiver operating characteristic analyses confirmed the sensitivity of these markers at these times. No urinary marker at acute stage of APN was correlated with the amount of future scarring, negating their predictive value. Conclusion. Urinary NGAL and Kim-1 could be helpful in diagnosing febrile urinary tract infection in children. 1. Introduction Febrile urinary tract infection (fUTI) has been reported in 1-2% of boys and 3–7% of girls younger than 6 years of age [1, 2]. Early diagnosis and treatment of fUTI are important, because missed or delayed diagnosis may result in the failure of appropriate treatment and possibly lead to long-term consequences, including renal scarring, hypertension, and chronic renal failure [3–5]. Unfortunately, the early and accurate diagnosis of fUTI is often challenging in children because of the lack of localizing signs and symptoms, difficulty in urine collection, and higher risks of contaminated samples. Although urine culture remains as the gold standard for diagnosing UTI [6], instant diagnosis is impossible due to the required incubation period of at least 24？h or more and another 2-3 days for complete identification of the bacteria, reducing the performance of this test in managing acutely sick children. Additionally, urine tests and imaging have unacceptable sensitivity and specificity in diagnosing fUTI. Hence, there is a clear need for a noninvasive, rapid, and highly sensitive test that will facilitate the early diagnosis of fUTI. Sensitive urine tests of potential biomarkers of fUTI