Prediction of moderate and high grade vesicoureteral reflux after a first febrile urinary tract infection in children: construction and internal validation of a clinical decision rule.

PURPOSE: Urinary tract infection leads to a diagnosis of moderate or high grade (III or higher) vesicoureteral reflux in approximately 15% of children. Predicting reflux grade III or higher would make it possible to restrict cystography to high risk cases. We aimed to derive a clinical decision rule to predict vesicoureteral reflux grade III or higher in children with a first febrile urinary tract infection. MATERIALS AND METHODS: We conducted a secondary analysis of prospective series including all children with a first febrile urinary tract infection from the 8 European participating university hospitals. RESULTS: A total of 494 patients (197 boys, reflux grade III or higher in 11%) were included. Procalcitonin and ureteral dilatation on ultrasound were significantly associated with reflux grade III or higher and then combined into a prediction model with an ROC AUC of 0.75 (95% CI 0.69-0.81). Given the prespecified constraint of achieving at least 85% sensitivity, our model led to the clinical decision rule, for children with a first febrile urinary tract infection cystography should be performed in cases with ureteral dilatation and serum procalcitonin level 0.17 ng/ml or higher, or without ureteral dilatation (ie ureter not visible) when serum procalcitonin level is 0.63 ng/ml or higher. The rule had 86% sensitivity (95% CI 74-93) with 47% specificity (95% CI 42-51). Internal cross-validation produced 86% sensitivity (95% CI 79-93) and 43% specificity (95% CI 39-47). CONCLUSIONS: A clinical decision rule was derived to enable a selective approach to cystography in children with urinary tract infection. The rule predicts high grade vesicoureteral reflux with approximately 85% sensitivity and avoids half of the cystograms that do not find reflux grade III or higher. Further validation is needed before its widespread use.

Procalcitonin is a predictor for high-grade vesicoureteral reflux in children: meta-analysis of individual patient data.

OBJECTIVE: To assess the predictive value of procalcitonin, a serum inflammatory marker, in the identification of children with first urinary tract infection (UTI) who might have high-grade (≥3) vesicoureteral reflux (VUR). STUDY DESIGN: We conducted a meta-analysis of individual data, including all series of children aged 1 month to 4 years with a first UTI, a procalcitonin (PCT) level measurement, cystograms, and an early dimercaptosuccinic acid scan. RESULTS: Of the 152 relevant identified articles, 12 studies representing 526 patients (10% with VUR ≥3) were included. PCT level was associated with VUR ≥3 as a continuous (P = .001), and as a binary variable, with a 0.5 ng/mL preferred threshold (adjusted OR, 2.5; 95% CI, 1.1 to 5.4). The sensitivity of PCT ≥0.5 ng/mL was 83% (95% CI, 71 to 91) with 43% specificity rate (95% CI, 38 to 47). In the subgroup of children with a positive results on dimercaptosuccinic acid scan, PCT ≥0.5 ng/mL was also associated with high-grade VUR (adjusted OR, 4.8; 95% CI, 1.3 to 17.6). CONCLUSIONS: We confirmed that PCT is a sensitive and validated predictor strongly associated with VUR ≥3, regardless of the presence of early renal parenchymal involvement in children with a first UTI.

Procalcitonin to reduce the number of unnecessary cystographies in children with a urinary tract infection: a European validation study.

OBJECTIVE: To validate high serum procalcitonin (PCT) as a predictor of vesicoureteral reflux (VUR) in children with a first febrile urinary tract infection (UTI). STUDY DESIGN: This secondary analysis of prospective hospital-based cohort studies included children ages 1 month to 4 years with a first febrile UTI. RESULTS: Of the 398 patients included in 8 centers in 7 European countries, 25% had VUR. The median PCT concentration was significantly higher in children with VUR than in those without: 1.6 versus 0.7 ng/mL (P = 10(-4)). High PCT (> or =0.5 ng/mL) was associated with VUR (OR: 2.3; 95% CI, 1.3 to 3.9; P = 10(-3)). After adjustment for all cofactors, the association remained significant (OR: 2.5; 95% CI, 1.4 to 4.4; P = 10(-3)). The strength of the relation increased with the grade of reflux (P = 10(-5)). The sensitivity of procalcitonin was 75% (95% CI, 66 to 83) for all-grade VUR and 100% (95% CI, 81 to 100) for grade > or =4 VUR, both with 43% specificity (95% CI, 37 to 48). CONCLUSIONS: High PCT is a strong, independent and now validated predictor of VUR that can be used to identify low-risk patients and thus avoid one third of the unnecessary cystourethrographies in children with a first febrile UTI.

Community-acquired urinary tract infection in hospitalized children: etiology and antimicrobial resistance. A comparison between first episode and recurrent infection.

Urinary tract infection (UTI) is common in infants and children, and Escherichia coli is the leading pathogen. The aims of this study were to compare first episode of UTI with recurrent infection, reveal organisms that cause UTI, uropathogen resistance, and presence of bacteria producing extended-spectrum ß-lactamase (ESBL). The first-UTI group included 456 children. E coli was the leading pathogen (80.5%), and Pseudomonas aeruginosa was found in 1.5%. The uropathogens were resistant to gentamicin (3.41%) and cefuroxime (5.71%), and highly resistant to cefamezin (37.39%). The recurrent-infection group included 106 children. E coli was also the leading pathogen, but 7.5% of the isolates were P aeruginosa (P = .002 compared with first-episode group); 6.6% were ESBL-producing bacteria compared with 1.1% in the first-episode group (P = .002). E coli is the leading pathogen in both groups. P aeruginosa and ESBL-producing bacteria were more common in the recurrent infection group.

Power Doppler sonography versus Tc-99m DMSA scintigraphy for diagnosing acute pyelonephritis in children: are these two methods comparable?

PURPOSE This study assessed the role of renal power Doppler ultrasonography (PDU) to identify acute pyelonephritis (APN) and to determine whether PDU can replace Tc-99m DMSA renal scintigraphy in the diagnosis of APN in children. METHODS A prospective study was conducted in 40 infants and young children (78 kidneys were evaluated) with a mean age of 25.9 months (range, 1 to 68 months) who were hospitalized with a first episode of high fever and bacteruria, possibly APN. All children were examined by PDU and Tc-99m DMSA within the first 3 days after admission. Patients with congenital abnormalities, hydronephrosis, and urinary reflux were excluded. RESULTS Twenty-seven of the 78 kidneys appeared abnormal on Tc-99m DMSA, and 20 of them were abnormal on PDU. Fifty-one of 78 kidneys were normal on Tc-99m DMSA, and 3 of 51 appeared diseased on PDU. The accuracy of PDU was 87%, sensitivity was 74%, and specificity was 94%. The positive predictive and negative predictive values were both 87%. When considering the numbers of lesions in 27 kidneys with positive Tc-99m DMSA studies (38 lesions), PDU did not disclose 16 lesions (false-negative results). Thus, the sensitivity of PDU for diagnosing lesions of APN decreased to 58%. CONCLUSIONS A positive PDU finding should obviate the use of Tc-99m DMSA in patients thought to have possible APN. However, because of a large number of false-negative results (26%) and underestimation of the number of pyelonephritic lesions (low sensitivity of 58%), PDU cannot replace Tc-99m DMSA in the diagnosis of APN in children.

Association of procalcitonin with acute pyelonephritis and renal scars in pediatric UTI.

BACKGROUND AND OBJECTIVE: Urinary tract infections (UTIs) are common childhood bacterial infections that may involve renal parenchymal infection (acute pyelonephritis [APN]) followed by late scarring. Prompt, high-quality diagnosis of APN and later identification of children with scarring are important for preventing future complications. Examination via dimercaptosuccinic acid scanning is the current clinical gold standard but is not routinely performed. A more accessible assay could therefore prove useful. Our goal was to study procalcitonin as a predictor for both APN and scarring in children with UTI. METHODS: A systematic review and meta-analysis of individual patient data were performed; all data were gathered from children with UTIs who had undergone both procalcitonin measurement and dimercaptosuccinic acid scanning. RESULTS: A total of 1011 patients (APN in 60.6%, late scarring in 25.7%) were included from 18 studies. Procalcitonin as a continuous, class, and binary variable was associated with APN and scarring (P < .001) and demonstrated a significantly higher (P < .05) area under the receiver operating characteristic curve than either C-reactive protein or white blood cell count for both pathologies. Procalcitonin ≥0.5 ng/mL yielded an adjusted odds ratio of 7.9 (95% confidence interval [CI]: 5.8-10.9) with 71% sensitivity (95% CI: 67-74) and 72% specificity (95% CI: 67-76) for APN. Procalcitonin ≥0.5 ng/mL was significantly associated with late scarring (adjusted odds ratio: 3.4 [95% CI: 2.1-5.7]) with 79% sensitivity (95% CI: 71-85) and 50% specificity (95% CI: 45-54). CONCLUSIONS: Procalcitonin was a more robust predictor compared with C-reactive protein or white blood cell count for selectively identifying children who had APN during the early stages of UTI, as well as those with late scarring.

Renal function in children with beta-thalassemia major and thalassemia intermedia.

In beta-thalassemia, profound anemia and severe hemosiderosis cause functional and physiological abnormalities in various organ systems. In recent years, there have been few published studies demonstrating proteinuria, aminoaciduria, low urine osmolality, and excess secretion of the tubular damage markers, such as urinary N-acetyl-D-glucosaminidase (U(NAG)) and beta2 microglobulin, in patients with thalassemia. The object of this study was to analyze renal tubular and glomerular function in pediatric patients with beta-thalassemia and to correlate the renal findings to iron overload. Thirty-seven patients with beta-thalassemia major and 11 with thalassemia intermedia were studied. Twelve children without iron metabolism disorders or renal diseases served as a control group. No difference in blood urea nitrogen (BUN), serum creatinine, creatinine clearance, electrolytes, fractional excretion of sodium and potassium, and tubular phosphorus reabsorption was found. Serum uric acid was equal in the two groups, but its urine excretion was significantly higher in the thalassemic group. U(NAG) and U(NAG) to creatinine ratio (U(NAG/CR)) were elevated in all patients with thalassemia compared with the control group (p < 0.001) and were directly correlated to the amount of transfused iron but not to actual ferritin level. We found that renal tubular function is impaired in children with beta- thalassemia major and intermedia. It is not known whether these functional abnormalities would have any long-term effects on the patients. Further studies are needed, and means of preventing these disturbances should be sought.

Tubular and glomerular function in children after renal transplantation.

Glomerular and tubular function of transplanted kidneys were assessed in 46 children aged 15.7 +/- 4.6 yr, 4.2 +/- 2.8 yr after renal transplantation. There were 34 cadaveric, and 12 living-related donors. Twelve patients (26%) had acute episodes (acute tubular necrosis, rejection, or urinary tract infection) during follow-up. All patients were on triple immunosuppression. The mean serum creatinine was 1.5 +/- 0.6 mg/dL. Creatinine clearance (Ccreat) calculated from a 24-h urine collection was 48.0 +/- 19.7 mL/min/1.73 m(2), and that estimated from the Schwartz formula, 61.0 +/- 22.5 mL/min/1.73 m(2). A positive correlation was found between the calculated and estimated clearances. Mean urine concentrating ability was 487 +/- 184 mOsmol/kg, with a value lower than 400 mOsmol/kg in 35% of patients. There was a positive correlation between urine osmolality and estimated Ccreat. Metabolic acidosis (bicarbonate <22 mmol/L) was found in 41% of patients, with relatively alkaline urine and high chloride level. Fractional excretion (FE) of sodium was above 1% in 68% of patients (mean 1.66 +/- 1.06%), and FE(Mg) was above 3% (mean 10.9 +/- 5.2%) in 93% of patients. Tubular reabsorption of phosphate (TP)/glomerular filtration rate (GFR) was 3.2 +/- 0.8 mg/dL glomerular filtrate (GF). FE(K), FE(UA), and Ca/creatinine in urine were normal. There were no functional group differences between the cadaveric and living-related kidneys. Significant group differences were found in those with acute episodes and those with a normal course. Estimated Ccreat was 54 +/- 20 vs. 67 +/- 20 mL/min/1.73 m(2) in the acute episodes and the normal course groups, respectively. Also, the FE(NA), FE(UA), and FE(Mg) were higher in the acute episodes group -2.3 +/- 1.6, 10.6 +/- 4.4, and 14.8 +/- 6.5%, respectively, compared with the normal course group -1.4 +/- 0.6, 8.2 +/- 2.8, and 9.6 +/- 4.0%, respectively. There were no between-group differences in plasma bicarbonate, FE(K), TP/GFR, and urine osmolality. We believe that most, if not all tubular dysfunctions in the transplanted kidney are secondary to renal failure and interstitial damage from acute episodes and nephrotoxic drugs. These dysfunctions are similar to those in chronic renal failure, where interstitial fibrosis plays a role in kidney function deterioration.

Procalcitonin as a marker of acute pyelonephritis in infants and children.

In the absence of specific symptomatology in children, the early diagnosis of acute pyelonephritis is a challenge, particularly during infancy. In an attempt to differentiate acute pyelonephritis from lower urinary tract infection (UTI), we measured serum procalcitonin (PCT) levels and compared these with other commonly used inflammatory markers. We evaluated the ability of serum PCT levels to predict renal involvement, as assessed by dimercaptosuccinic acid (DMSA) scintigraphy. Serum C-reactive protein (CRP), leukocyte counts, and PCT levels were measured in 64 children admitted for suspected UTI. Renal parenchymal involvement was assessed by (99m)Tc-DMSA scintigraphy in the first 7 days after admission. In acute pyelonephritis, the median PCT level was significantly higher than in the lower UTI group (3.41, range 0.36-12.4 microg/l vs. 0.13, range 0.02-2.15 microg/l, P<0.0001). In these two groups, respectively, median CRP levels were 120 (range 62-249 mg/l) and 74.5 (range 14.5-235 mg/l, P=0.012) and leukocyte counts were 15,910/mm(3) (range 10,200-26,900) and 14,600/mm(3) (range 8,190-26,470, P=0.34). For the prediction of acute pyelonephritis, the sensitivity and specificity of PCT were 94.1% and 89.7%, respectively; CRP had a sensitivity of 100%, but a specificity of 18.5%. We conclude that serum PCT may be an accurate marker for early diagnosis of acute pyelonephritis.

Power Doppler ultrasonography in the diagnosis of acute childhood pyelonephritis.

In the absence of specific symptomatology in children, the early diagnosis of acute pyelonephritis (APN) is a challenge, particularly during infancy. In an attempt to differentiate APN from lower urinary tract infection (UTI), we evaluated the ability of power Doppler ultrasonography (PDU) to predict renal parenchymal involvement, as assessed by dimercaptosuccinic acid ((99m )Tc-DMSA) scintigraphy. The study comprised 62 patients, 46 girls and 16 boys, aged 2 weeks to 5 years, admitted to the pediatric department with febrile UTI. All children were examined by PDU and DMSA scintigraphy within the first 3 days of admission. In the group of 31 patients with one or more DMSA scan abnormalities, the PDU showed a matching perfusion defect in 27 (87%). Of 26 children with normal DMSA scintigraphy, the PDU evaluation was also normal in 24. The sensitivity and specificity of PDU for the detection of affected kidneys were 87% and 92.3%, and the positive predictive value and negative predictive value were 93.1% and 85.7%, respectively. These data indicate the PDU has a high sensitivity and specificity for differentiating APN from lower UTI and may be a useful and practical tool for the diagnosis of APN in infants and children.