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-glucosami nidase (NAG; early index of renal proximal tubular damage) and epidermal gr owth factor (EGF; early index of renal damage repair) in paediatric patient s with and without vesico-ureteric reflux (VUR) receiving prophylactic cefi xime for recurrent urinary tract infections (UTIs). Design and Setting: Urinary levels of NAG and EGF in children, with and wit hout VUR, with recurrent UTIs receiving prophylactic cefixime were compared with normal paediatric laboratory values in a university paediatric depart ment. All children were followed during an ordinary admission or in a day h ospital. Participants and Treatment: The study population consisted of 27 patients ( 15 males, 12 females; mean age 1.73 +/- 1.43 years) followed in the Paediat ric Department of the University of Verona for recurrent UTIs. All patients had experienced at least two episodes of UTIs in the previous 2 months. Pa tients received antibiotic prophylaxis with cefixime (4 mg/kg bodyweight), administered as a single bedtime dose. The overall duration of the treatmen t ranged from I to 2 months. Urine samples and cultures were taken immediat ely prior to voiding urethrocystography via the bladder catheter and were i mmediately frozen at -20 degreesC. NAG activity and EGF levels in the urine were determined using a colorimetric assay and a radioimmunoassay, respect ively. 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 pre sented with normal routine laboratory values, in particular serum creatinin e and BUN levels. In addition, urine tests and cultures yielded normal valu es in III cases. In patients without VUR receiving prophylactic cefixime, t he mean [ standard deviation (SD)] NAG level was 0.50 +/- 0.30 U/mmol creat inine (range 0.05 to 1.17). Only one of 20 patients had a slight increase a bove 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 havi ng abnormally elevated NAG values. The difference in NAG levels between the two groups was statistically significant (p < 0.001). In patients receivin g prophylactic cefixime without VUR (group 1), the mean urinary EGF level w as 25.06 +/- 16.05 <mu>g/L (range 1.58 to 49.63). In patients receiving pro phylaxis with cefixime with VUR treatment (group 2), the mean (+/- SD) urin ary EGF level was 38.23 +/- 33.99 mug/L (range 14.4 to 107). Urinary EGF le vels were not statistically different between group I and normal levels, wh ereas in group 2, EGF levels were significantly higher than normal levels o r those of group I (p < 0.05, both comparisons). Conclusions: Prophylactic treatment with cefixime was well tolerated, inclu ding renally, in children with recurrent UTIs without VUR. Renal tolerabili ty was assessed using a sensitive measure of the early signs of nephrotoxic ity, such as urinary NAG values, and markers of damage repair, such as urin ary EGF levels. The presence of VUR in patients was associated with signifi cant renal proximal tubular damage, as reflected in elevated urinary NAG va lues. The high urinary EGF values probably reflect the compensatory repair action of the kidney in patients with VUR. In conclusion, in clinical pract ice, cefixime may be safely suggested for antibiotic prophylaxis in paediat ric patients with recurrent UTIs.