In this study the investigators will determine whether corticosteroids given at the time of urinary tract infection help prevent permanent damage to the kidneys.

Because host inflammatory response is the final and most important step in the formation of renal scars, the use of anti-inflammatory agents may be the best strategy to reduce renal scarring. In animal studies, the use of corticosteroids has been shown to be effective in preventing post-pyelonephritic scarring. We will conduct a randomized, double-blind, placebo-controlled trial to determine the efficacy of 3 days of daily adjuvant dexamethasone on the incidence of renal scarring 4 to 6 months after a first febrile urinary tract infection (UTI). We hypothesize that the proportion of children with UTI who develop renal scarring will be lower among children who are treated with both dexamethasone and antibiotics as compared with children treated with antibiotics alone.

Inclusion Criteria:

• Age: 2 months to 6 years
• Pyuria: ≥10 white blood cells per cubic millimeter (WBC/mm3) in an uncentrifuged specimen or ≥5 white blood cells per high power field (WBC/hpf) in a centrifuged specimen or ≥1+ leukocyte esterase (LE) on dipstick
• Fever: documented temperature of at least 101 °F or 38.3°C, measured anywhere on the body either at home or at doctor's office within 24 hours of diagnosis

Exclusion Criteria:

• Other concurrent systemic bacterial infection(s) such as meningitis or pneumonia;
• Planned admission to intensive care unit;
• Known bacteremia;
• Previous protocol defined UTI;
• Known major urinary tract anomalies (severe hydronephrosis, ureterocele, urethral valve, solitary or profoundly small kidney, multicystic dysplastic kidney, neurogenic bladder, pelvic or fused kidney);
• Congenital/acquired immunodeficiency;
• Bag urine collection
• Chronic diseases that could potentially interfere with response to therapy, such as chronic gastrointestinal conditions (i.e. malabsorption, inflammatory bowel disease), liver/kidney failure;
• Allergy to dexamethasone
• Antibiotic use within 7 days of enrollment (except if given in the last 48 hours)
• Systemic use of corticosteroids or other immunomodulating agents within 14 days of enrollment
• History of Kawasaki disease
• Sickle cell disease (not trait)

546 children were randomized; 271 to Adjuvant Dexamethasone and 275 to Placebo. 3 of the 271 were found ineligible post randomization & were withdrawn by the PI. 71 & 87 participants in the respective groups had negative/indeterminate cultures. The remaining 197 & 188 participants had positive urine cultures & were the basis for the analysis.

Parents were called on days 2,3 and 4 to monitor for adverse events (AEs) after administration of study medication. If the child remained febrile by day 4, daily phone calls were made until the child was afebrile. Monthly phone calls monitored for AEs; parents were reminded to call the 24-hour study line with concerns regarding their child's health. Parents were interviewed at interim visits and at the final 6-month study contact to elicit AEs.

Staff reviewed the child's medical record for any medical care visits since their last study contact for any adverse events. If child was seen or had any new symptoms within 2 weeks of taking study product, the symptoms were reported as adverse events. After 2 weeks of taking study product, if a child was seen for fever or urinary symptoms but not diagnosed with a urinary tract infection these symptoms were reported as an adverse event.