Urinary excretion of N-acetyl-beta-D-glucosaminidase and epidermal growth factor in paediatric patients receiving cefixime prophylaxis for recurrent urinary tract infections

Objective: To determine the urinary excretion of N-acetyl-beta -D-glucosaminidase (NAG; early index of renal proximal tubular damage) and epidermal growth factor (EGF; early index of renal damage repair) in paediatric patients with and without vesico-ureteric reflux (VUR) receiving prophylactic cefixime for recurrent urinary tract infections (UTIs). Design and Setting: Urinary levels of NAG and EGF in children, with and without VUR, with recurrent UTIs receiving prophylactic cefixime were compared with normal paediatric laboratory values in a university paediatric department. All children were followed during an ordinary admission or in a day hospital. Participants and Treatment: The study population consisted of 27 patients (15 males, 12 females; mean age 1.73 +/- 1.43 years) followed in the Paediatric Department of the University of Verona for recurrent UTIs. All patients had experienced at least two episodes of UTIs in the previous 2 months. Patients received antibiotic prophylaxis with cefixime (4 mg/kg bodyweight), administered as a single bedtime dose. The overall duration of the treatment ranged from I to 2 months. Urine samples and cultures were taken immediately prior to voiding urethrocystography via the bladder catheter and were immediately frozen at -20 degreesC. NAG activity and EGF levels in the urine were determined using a colorimetric assay and a radioimmunoassay, respectively. The urinary creatinine level was determined using the Jaffe kinetic colorimetric method at a constant reaction temperature of 37 degreesC. The values obtained were compared with the Laboratory's own reference standards for paediatric patients. Main Outcome Measures and Results: All children in the study population presented with normal routine laboratory values, in particular serum creatinine and BUN levels. In addition, urine tests and cultures yielded normal values in III cases. In patients without VUR receiving prophylactic cefixime, the mean [ standard deviation (SD)] NAG level was 0.50 +/- 0.30 U/mmol creatinine (range 0.05 to 1.17). Only one of 20 patients had a slight increase above the normal range. In patients with VUR, the urinary NAG level was 2.55 +/- 1.66 U/mmol creatinine (range 1.37 to 6), with all seven patients having abnormally elevated NAG values. The difference in NAG levels between the two groups was statistically significant (p < 0.001). In patients receiving prophylactic cefixime without VUR (group 1), the mean urinary EGF level was 25.06 +/- 16.05 <mu>g/L (range 1.58 to 49.63). In patients receiving prophylaxis with cefixime with VUR treatment (group 2), the mean (+/- SD) urinary EGF level was 38.23 +/- 33.99 mug/L (range 14.4 to 107). Urinary EGF levels were not statistically different between group I and normal levels, whereas in group 2, EGF levels were significantly higher than normal levels or those of group I (p < 0.05, both comparisons). Conclusions: Prophylactic treatment with cefixime was well tolerated, including renally, in children with recurrent UTIs without VUR. Renal tolerability was assessed using a sensitive measure of the early signs of nephrotoxicity, such as urinary NAG values, and markers of damage repair, such as urinary EGF levels. The presence of VUR in patients was associated with significant renal proximal tubular damage, as reflected in elevated urinary NAG values. The high urinary EGF values probably reflect the compensatory repair action of the kidney in patients with VUR. In conclusion, in clinical practice, cefixime may be safely suggested for antibiotic prophylaxis in paediatric patients with recurrent UTIs.