OBJECTIVE:To revise the American Academy of Pediatrics practice parameter regarding the diagnosis and management of initial urinary tract infections (UTIs) in febrile infants and young children.METHODS:Analysis of the medical literature published since the last version of the guideline was supplemented by analysis of data provided by authors of recent publications. The strength of evidence supporting each recommendation and the strength of the recommendation were assessed and graded.RESULTS:Diagnosis is made on the basis of the presence of both pyuria and at least 50,000 colonies per mL of a single uropathogenic organism in an appropriately collected specimen of urine. After 7 to 14 days of antimicrobial treatment, close clinical follow-up monitoring should be maintained to permit prompt diagnosis and treatment of recurrent infections. Ultrasonography of the kidneys and bladder should be performed to detect anatomic abnormalities. Data from the most recent 6 studies do not support the use of antimicrobial prophylaxis to prevent febrile recurrent UTI in infants without vesicoureteral reflux (VUR) or with grade I to IV VUR. Therefore, a voiding cystourethrography (VCUG) is not recommended routinely after the first UTI; VCUG is indicated if renal and bladder ultrasonography reveals hydronephrosis, scarring, or other findings that would suggest either high-grade VUR or obstructive uropathy and in other atypical or complex clinical circumstances. VCUG should also be performed if there is a recurrence of a febrile UTI. The recommendations in this guideline do not indicate an exclusive course of treatment or serve as a standard of care; variations may be appropriate. Recommendations about antimicrobial prophylaxis and implications for performance of VCUG are based on currently available evidence. As with all American Academy of Pediatrics clinical guidelines, the recommendations will be reviewed routinely and incorporate new evidence, such as data from the Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR) study.CONCLUSIONS:Changes in this revision include criteria for the diagnosis of UTI and recommendations for imaging.

The diagnosis and proper management of u r inary tract infections (UTIs) in infants and children is an important aspect of pediatric practice. Dr. Hellerstein has provided a concise, affordable, and readable monograph on this subject for the practicing pediatrician. As common as these infections are, areas of controversy cont inue and several are discussed: optimal methods for collecting noncontaminated specimens in infants, when and in whom radiographic studies should be done, the significance of vesicoureteral reflux, the optimal duration of therapy, and when to institute chemoprophylaxis for recurrent infections.

The purpose of this study was to validate serum creatinine (SCr) concentrations assayed in the Central Biochemistry Laboratory of the National Institutes of Health (NIH)-funded Chronic Kidney Disease in Children (CKiD) study utilizing an enzymatic assay (Siemens Advia 2400) against a method traceable to reference isotope dilution mass spectroscopy (IDMS) developed by the National Institute of Standards and Technology (NIST). High-performance liquid chromatography (HPLC) measured SCr after external validation utilizing IDMS-based standard reference materials. Sera from the first 201 subjects enrolled in CKiD were analyzed and compared for creatinine concentration by enzymatic and HPLC methods. Fifty "normal" pediatric sera were subsequently analyzed. Finally, a "pediatric" reference standard was prepared and examined for accuracy and precision. Enzymatic SCr concentrations (median 1.4 mg/dl) of CKiD subjects were well correlated with HPLC (r = 0.984) but were slightly higher (+7%; p < 0.001). Agreement was poorer at lower SCr (median 0.4 mg/dl) when using samples from normal children and the "pediatric" reference standard. However, the Roche enzymatic assay was comparable with HPLC in accuracy and precision. Referring physicians should be aware of the accuracy and reproducibility of their laboratory's SCr assay. Our enzymatic assay agreed well with HPLC in CKiD subjects with elevated SCr. We suggest that NIST develop a pediatric SCr standard reference material for use by assay manufacturers to improve accuracy and precision of assays at the low SCr levels observed in most pediatric patients.

The study provides the pediatric practitioner with a tool to determine whether the child with an apparently normal solitary kidney requires an in-depth investigation. Medical records from January 1, 1995 to December 31, 2006 identified 96 children with solitary kidneys and showed 78 with a normal appearing, hypertrophied solitary kidney. Study groups included (1) children 1 to 2 years, (2) girls older than 2 years and boys 2 to 13 years, and (3) boys older than 13 years. Serum creatinine concentrations and estimated glomerular filtration rate were calculated for each group. The mean serum creatinine concentrations in group 1 was 0.4 ± 0.1 mg/dL, group 2 was 0.6 ± 0.2 mg/dL, and group 3 was 1.1 ± 0.2 mg/dL. An estimated glomerular filtration rate 2 SD below the mean suggests further investigation. An estimated glomerular filtration rate 2 SD below the mean was 78 mL/min/1.73m 2 in group 1, 73 mL/min/1.73m 2 in group 2, and 70 mL/min/1.73m 2 in group 3.

Renal functional reserve (RFR) has been measured in 14 RFR studies on 12 pediatric patients. These children had evidence of a decrease in the number of nephrons due to upper urinary tract damage or absence of one kidney. The studies were done because the children were considered at risk for glomerular hyperfiltration in the absence of evidence of chronic kidney disease. They had normal serum electrolytes, normal urinalyses and glomerular filtration rates above 60 ml/min/1.73 m(2). Seven studies showed an absence of glomerular hyperfiltration, two studies confirmed glomerular hyperfilration and one study fell into the "questionable" range for glomerular hyperfiltration. The study was technically unsatisfactory in four instances, two of which were in children with gross anatomic abnormalities. The report illustrates the use of RFR in evaluation of children in a pediatric renal clinic.

This report is to provide primary care physicians with a convenient method for identifying children with impaired kidney function. This is important because of the prevalence of chronic kidney disease in adults and because intervention may delay disease progression. The glomerular filtration rate (GFR) measured using cimetidine clearance and calculated using height and serum creatinine concentration were compared during 222 clearance studies in 32 pediatric patients over 8 years. A child 1 year or older with a calculated GFR < 60 mL/min/ 1.73 m(2) has a significantly reduced GFR and should be referred to a pediatric nephrologist for further evaluation.

Purpose of review The evaluation and management of urinary tract infections in infants and children is undergoing changes due to the impact of evidence-based studies and new technology.Recent findings The uncircumcised male infant is at increased risk for a urinary tract infection, but there is marked difference in the frequency of circumcision carried out to lower the risk of infection in the United States compared with Europe. Commentaries presenting different interpretations of the current data make for interesting reading and present the many sides of this issue. Vesicoureteric reflux, previously viewed as the major risk factor for acquired renal damage, now shares this role with nonreflux nephropathy. Procalcitonin has been evaluated as a biochemical tool to identify patients at risk for kidney damage, with dime rcaptosucci n ic acid scintigraphy as the reference method to detect renal scarring.Summary The previously accepted concept that vesicoureteric reflux as detected radiologically is almost always the key factor in acquired renal injury secondary to a urinary tract infection is no longer accepted. Current studies show that nonreflux nephropathy occurs as often as reflux nephropathy. There is now a question of the value of imaging studies designed to identify vesicoureteric reflux and of the use of suppressive antibiotics for vesicoureteric reflux. There exist useful evidence-based studies for antibiotic therapy for upper and lower tract urinary tract infections, but no such data are available for guidance in selecting imaging studies for the infant or child with a first febrile urinary tract infection.

The purpose of this study was to describe the reproducibility of timed-urine collections for renal clearance studies and the effect variations in urine collection has on measurement of glomerular filtration rate (GFR). Data from 222 cimetidine clearance studies (GFR-Cim) were obtained from 32 pediatric renal patients over a period of 8 years. There were three to 18 studies per child aged 4.8 years to 21 years at the time of a study. The urinary creatinine excretion rate is measured during supervised urine collection periods. The creatinine excretion rates in each child were compared to obtain data on the reproducibility of the urine collections. The coefficient of variation (CV) of the creatinine excretion rate is approximately 10% in both children and adults. The variation in GFR to be expected during repeated renal clearance studies in subjects with stable GFR, using voided urine collections, was similar in children and adults, with a CV of 12% to 14%.

Glomerular filtration rate (GFR) was measured in 216 studies in 151 children using the cimetidine protocol. This was compared with the GFR calculated using Léger’s pharmacokinetic equation and with that calculated using k*L/[Cr]s (constant × length in centimeters divided by serum creatinine concentration). The GFR calculated using the equation GFR=k*L/[Cr]s yielded a closer approximation to the measured GFR than that using Léger’s pharmacokinetic equation. Currently there is focus on screening children for decreased GFR to identify those with asymptomatic chronic kidney disease at a time when intervention may delay progression to chronic renal failure. This study showed close approximation of the calculated GFR with the measured GFR using the equation GFR=k*L/[Cr]s, when the values for k were determined in the laboratory in which creatinine was measured.

Renal functional reserve was measured during 89 studies in 78 children as the difference between the baseline glomerular filtration rate (GFR) and that following a protein meal. GFR was measured using creatinine as the filtration marker in children pre-treated with cimetidine. The children had been on a diet free of meat, fish, and fowl for 24 h. The protein meal to stimulate GFR was derived from milk, cheese, eggs, and baked goods. The increase in GFR following the protein meal was due mainly to an increase in the glomerular filtration of creatinine, with a small contribution by decreased serum creatinine concentration. This study confirmed that renal functional reserve can be measured using a meat-free protein meal to stimulate GFR. The protocol employed is a relatively noninvasive and inexpensive procedure for identifying glomerular hyperfiltration in children.

Glomerular filtration rate (GFR) and urine and serum concentrations of cystatin C and creatinine were measured in 40 boys and 42 girls. The fractional excretion of cystatin C (FE Cyst C) increased in proportion to the decrease in GFR. Since serum creatinine concentration (S-Creatinine) in the numerator of the fractional excretion equation and serum cystatin C concentration (S-Cystatin C) in the denominator have similar numerical values, they cancel out. The result is an equation in which the FE Cyst C is equal to the ratio of urinary cystatin C to urinary creatinine (u[cystatin-C/Cr]). The ratio of u[cystatin C/Cr] was compared with GFR. Using a receiving operating characteristic (ROC) plot, the data showed that a ratio of u[cystatin C/Cr]*100 that is ≥0.100 has a sensitivity of 90.0% for identification of children with GFR ≤60 ml/min per 1.73 m2. The false-positive rate is 16.1%. The u[cystatin C/Cr] ratio is a reliable screening tool for detecting decreased GFR that does not require a serum sample.

One hundred forty-four children with a clinical diagnosis of overactive bladder were observed for a mean of 3.15 ± 1.92 years. Initial management consisted of a behavioral modification program that included increased fluid intake, a timed voiding schedule and, if applicable, treatment of constipation. Those who failed to improve with the preceding intervention within 10 days to 2 weeks received an anticholinergic medication. Follow-up information was obtained by telephone. Caretakers and/or patients were asked a standard set of questions. The outcome with respect to urinary urgency, urinary frequency, daytime incontinence, posturing and urinary tract infections was recorded. After an average follow-up period of 3 years, 68 (47.2%) of the 144 children recovered from all symptoms of overactive bladder and 61 (42.4%) had decreased symptoms. Fifteen of the children, or 10.4%, still had all of the symptoms originally associated with overactive bladder. Children who had posturing as one of their symptoms had a significantly increased risk of urinary tract infection.

This review focuses on antibiotic treatment of acute urinary tract infections (UTIs) in children who are neurologically and anatomically intact. Neonates younger than 28 days with a febrile UTI should be hospitalized, given supportive care and treated with parenteral amoxicillin and cefotaxime. Following a good response to 3 to 4 days of parenteral antibacterial therapy, outpatient treatment with an oral antibiotic should be given to complete 14 days of therapy. Infants from 28 days to 3 months who appear clinically ill with a febrile UTI should be hospitalized, receive supportive care and parenteral administration of a 3(rd) generation cephalosporin or gentamicin. When these infants are clinically improved and afebrile for 24 hours they should be discharged to complete 14 days of therapy with an oral antibiotic. Infants from 28 days to 3 months of age who are not acutely ill with a febrile UTI may be managed as outpatients. Ceftriaxone or gentamicin should be administered parenterally and given each 24 h until the infant is afebrile for 24 hours. Fourteen days of therapy should be completed with an oral antibiotic. Children with complicated pyelonephritis should be hospitalized, receive supportive care and parenteral ceftriaxone or gentamicin each 24 hours until clinically improved and without fever for 24 hours. They should then complete 10 to 14 days of therapy with an oral antibiotic as an outpatient. Children with uncomplicated pyelonephritis should be rehydrated in the outpatient department (if necessary) and receive parenteral ceftriaxone or gentamicin each 24 hours until without fever for 24 hours. If clinically improved they should receive an oral antibiotic to complete 10 to 14 days of therapy. Children with cystitis who are only mildly symptomatic should be managed with supportive care until the result of the urine culture and sensitivity are available. Children with cystitis who are moderately to severely symptomatic should receive an oral antibiotic and supportive care immediately. If the therapy is effective, children with cystitis should show a good clinical response in 2 to 3 days. If the response is satisfactory and the culture shows an organism susceptible to the antibiotic used, complete 5 to 7 days of treatment with the oral antibiotic.

The goals of this study were to describe the pattern of voiding disorders in children in our community, to describe clinical criteria for making the specific diagnoses, and to comment on management. The medical records of 226 children referred because of voiding dysfunction or urinary tract infections (UTI) were evaluated. Children with normal voiding patterns when uninfected, with monosymptomatic nocturnal enuresis, and with known neurologic or anatomic abnormalities were excluded. Detrusor instability, an abnormal voiding pattern characterized by urgency with or without frequency, was the diagnosis in 175 of the 226 children. Children with detrusor instability who used various posturing maneuvers to avoid urinary incontinence had a significantly higher incidence of UTIs than those who did not attempt to obstruct urine outflow. Detrusor instability appeared to be secondary to constipation in 19 of the children. The other diagnoses were extraordinary daytime urinary frequency, infrequent voiding, monosymptomatic daytime wetting, transient voiding dysfunction, giggle incontinence, dysfunctional voiding, and unexplained dysuria. It is concluded that children with detrusor instability who use posturing maneuvers to avoid incontinence are at high risk for recurrent UTIs. Constipation is 1 cause of detrusor instability. Dysfunctional voiding, the form of voiding dysfunction most likely to result in renal damage, was present in only 2 of 226 children seen for voiding disorders.

Successful treatment of an episode of acute pyelonephritis.,or cystitis in a child is usually no problem. The challenge is to prevent kidney damage and recurrent infections by identifying risk factors. An ultrasonogram and a cystogram of the urinary tract are recommended for the child with a first episode of acute pyelonephritis. These studies should identify children with obstructive abnormalities and vesicoureteric reflux (VUR). Other interventions that may be helpful include circumcision of the newborn male delivered in a hospital the use of prophylactic antibiotics for children with VUR who have a history of urinary tract infection, avoidance of broad-spectrum antibiotics for treatment of upper respiratory tract infections except when essential, careful management of children with voiding dysfunction,and prophylactic measures for sexually active adolescent girls who are prone to urinary tract infections.

The outcome of using prophylactic antibiotics in children considered at risk for a urinary tract infection (UTI) was documented in 66 children during the period of suppressive antibiotics and for a follow-up period of 3.7+/-2.2 years (range 0.92-9.83 years). A breakthrough UTI occurred in 13 girls but none of the boys during the initial course of prophylactic antibiotics. During the follow-up period, 33 girls and 5 boys had no recurrence of infection, while 25 girls and 3 boys had UTIs. Statistical analysis of the data using chi-square and risk estimate relating factors for infection to the occurrence of a UTI showed that during the period of initial prophylactic antibiotic there was significant risk of infection among children with voiding dysfunction and abnormal kidneys and during the follow-up there was increased risk of infection among those with voiding dysfunction and vesicoureteric reflux (VUR) of grade 3 or greater severity. Lesser grades of VUR and constipation did not significantly increase the risk of UTI. These observations should be useful in developing a study to define the risks and benefits of prophylactic antibiotic in "at-risk" children.

Unilateral multicystic dysplastic kidney (MCDK) in a normal infant is believed to be a sporadic disorder, with an incidence of about 1 in 4,300 live births. Isolated unilateral MCDK occurring in a family without other genitourinary abnormalities has not been described. We report a family in which isolated unilateral MCDK occurred in a woman and her two children. The mother presented with a palpable abdominal mass during infancy, which on excision was found to be a MCDK. Both the children were found to have MCDK on prenatal ultrasonography, which was later confirmed on postnatal evaluation. The MCDK in the children continues to involute on follow-up urinary tract ultrasonography. The inheritance of MCDK appears to be autosomal dominant in this family.