calca-protein--human and Vesico-Ureteral-Reflux

Pyelonephritis is a common bacterial disease in young children and is a serious infection because of its potential to produce renal scarring. One of the concerns of physicians is therefore the diagnosis of uropathy at risk for recurrence of pyelonephritis, especially high-grade reflux. There are no French recommendations on imaging evaluation after a first episode of pyelonephritis. Voiding cystography was systematically proposed years ago and recommended by the American Academy of Pediatrics until 1999. This systematic strategy exposed all children to a painful, irradiating exam, and exposed them to urinary tract infection. The American recommendations changed in 2011 and cystography is now only proposed to children with recurrence of pyelonephritis or with ultrasound abnormalities. A collaborative review of the literature involving the Pediatric Emergency, Nephrology and Surgery Departments at Necker-Enfants-Malades Hospital led us to propose an algorithm for imaging after the first episode of pyelonephritis in children. This algorithm was based on data from the past medical history (results of prenatal ultrasonography or recurrence of pyelonephritis), the results of the ultrasound exam at the time of diagnosis, and the procalcitonin concentration, to limit the indications for voiding cystography, limiting risk for delaying high-grade reflux diagnosis. Children with low risk for high-grade reflux can be followed up with an ultrasound exam 6 months after acute infection.

Topics: Algorithms; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Cooperative Behavior; Female; Follow-Up Studies; Humans; Hydronephrosis; Infant; Infant, Newborn; Interdisciplinary Communication; Male; Pregnancy; Protein Precursors; Pyelonephritis; Recurrence; Risk Factors; Ultrasonography, Prenatal; Vesico-Ureteral Reflux

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).. 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.. 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).. 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.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Child, Preschool; Dilatation, Pathologic; Humans; Infant; Infant, Newborn; Kidney; Predictive Value of Tests; Protein Precursors; Radiography; Radionuclide Imaging; Radiopharmaceuticals; Sensitivity and Specificity; Technetium Tc 99m Dimercaptosuccinic Acid; Ultrasonography; Urinary Bladder; Urinary Tract; Urinary Tract Infections; Vesico-Ureteral Reflux

An estimated 7% of girls and 2% of boys will have a urinary tract infection before 6 years of age, and between 20 and 40% of these children are diagnosed with vesicoureteral reflux. Reflux is a risk factor for recurrent infections and renal scarring, which can lead to hypertension and kidney failure. Pediatric guidelines recommend routine voiding cystourethrography, but this is a painful and expensive examination that exposes children to radiation. Reliable non invasive markers of reflux would therefore be extremely useful. Ultrasonography and clinical decision rules have poor sensitivity for vesicoureteral reflux. In contrast, the level of procalcitonin, a marker of the severity of bacterial infections, is a good predictor of cystographic findings in children with a first febrile urinary tract infection. Indeed, a procalcitonin level below 0.5 ng/ml predicted the absence of radiological reflux with a sensitivity of more than 75% in the French princeps study. This was validated by a prospective European study, in which sensitivity reached 100% for high-grade reflux. Procalcitonin assay can thus avoid voiding cystourethrography in 40 to 50% of young children with febrile urinary tract infections.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Humans; Kidney; Protein Precursors; Ultrasonography; Urinary Tract Infections; Vesico-Ureteral Reflux

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.. 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 dimercaptosuccinic acid scintigraphy as the reference method to detect renal scarring.. 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.

Topics: Acute Disease; Calcitonin; Calcitonin Gene-Related Peptide; Child; Circumcision, Male; Female; Fever; Glycoproteins; Humans; Kidney; Male; Protein Precursors; Risk Factors; Ultrasonography; Urinary Tract Infections; Vesico-Ureteral Reflux

Procalcitonin is a sensitive biomarker for bacterial infections. Recent studies show a correlation between serum procalcitonin level and vesicoureteral reflux (VUR). The aim of this study was to evaluate the predictive value of procalcitonin in diagnosis of VUR in children with febrile urinary tract infection.. One hundred and eight children aged 2 month to 12 years with febrile urinary tract infection were evaluated. Serum procalcitonin was measured before initiation of antibiotics. Standard voiding cystourethrography (VCUG) was performed in all children as the gold standard for detection of VUR. Sensitivity and specificity of a high procalcitonin level was evaluated using the receiver operating characteristic curve.. Forty-eight patients (44%) had VUR at least in one kidney, including grade 1 to 2 in 12 patients (11.1%), grade 3 in 16 (14.8%), and grade 4 to 5 in 20 patients (18.5%). Procalcitonin level ranged from 0.05 ng/mL to 13.6 ng/mL. Procalcitonin level was significantly higher with increasing the grading of reflux. Comparing procalcitonin levels with VCUG results, a sensitivity of 97% and a specificity of 75% was obtained at a procalcitonin level of 0.59 ng/mL for diagnosis of VUR. There was a significant correlation between procalcitonin level and leukocytosis, erythrocyte sedimentation rate, and C-reactive protein.. A high procalcitonin level may be used for prediction of all grades of VUR in children with febrile urinary tract infection. A low procalcitonin level may be used for avoidance of unnecessary VCUG in some low-risk patients.

Topics: Blood Sedimentation; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Cross-Sectional Studies; Female; Humans; Infant; Leukocytosis; Male; Protein Precursors; Reproducibility of Results; Sensitivity and Specificity; Urinary Tract Infections; Vesico-Ureteral Reflux

We examined the ability of a procalcitonin (PCT) protocol to detect vesicoureteral reflux (VUR) and renal scarring (RS), evaluated procedural costs and radiation burden, and compared four representative guidelines for children with their first febrile urinary tract infection (UTI).. Children aged ≤2 years with their first febrile UTI who underwent renal ultrasonography (US), acute and late technetium-99m ((99m)Tc)-dimercaptosuccinic acid scan, and voiding cystourethrography were prospectively studied. The representative guidelines applied in a retrospective simulation included the American Academy of Pediatrics (AAP), National Institute of Clinical Excellence, top-down approach (TDA), and Italian Society of Pediatric Nephrology (ISPN). These were compared in terms of ability to detect abnormalities, procedural costs and radiation.. Of 278 children analyzed, 172 (61.9%) had acute pyelonephritis. There was VUR in 101 (36.3%) children, including 73 (26.3%) with grades III-V VUR. RS was identified in 75 (27.0%) children. To detect VUR, TDA and PCT had the highest sensitivity for grades I-V VUR (80.2%) and III-V VUR (94.5%), respectively, whereas AAP had the highest specificity for I-V VUR (77.4%) and III-V VUR (78.0%), respectively. TDA and PCT had the highest sensitivity (100%) for detecting RS. The highest cost and radiation dose was associated with TDA, whereas AAP had the least expenditure and radiation exposure. By multivariate analysis, PCT and VUR, especially grades III-V, were independent predictors of RS.. There is no perfect guideline for first febrile UTI children. The PCT protocol has good ability for detecting high-grade VUR and RS. If based on available imaging modalities and reducing cost and radiation burden, clinical suggestions in the AAP guidelines represent a considerable protocol.

Topics: Algorithms; Calcitonin; Calcitonin Gene-Related Peptide; Child, Preschool; Cohort Studies; Diagnostic Imaging; Fever; Humans; Infant; Kidney Diseases; Practice Guidelines as Topic; Protein Precursors; Pyelonephritis; Radiopharmaceuticals; Technetium Tc 99m Dimercaptosuccinic Acid; Ultrasonography; Urinary Tract Infections; Vesico-Ureteral Reflux

Procalcitonin is a reliable and specific marker of bacterial infections such as urinary tract infection. Some authors suggest measurement of serum procalcitonin as a predictor of vesicoureteral reflux (VUR). We investigated this association in children admitted because of acute pyelonephritis.. Forty-eight children with the first febrile urinary tract infection were included. Twelve patients had low-grade VUR, 9 patients had high-grade VUR, and 27 patients did not have any VUR in their imaging assessment.. There was a significant association between high-grade VUR and higher levels of procalcitonin (P = .04). The sensitivity of a procalcitonin level of 0.31 ng/mL or greater was 90% and the specificity was 32% for diagnosis of high-grade VUR.. We concluded that serum procalcitonin concentration is a sensitive and promising predictor of high-grade VUR.

Topics: Acute Disease; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child, Preschool; Female; Humans; Infant; Male; Predictive Value of Tests; Prospective Studies; Protein Precursors; Pyelonephritis; Risk Factors; Severity of Illness Index; Up-Regulation; Vesico-Ureteral Reflux

The aim of this article was to assess the usefulness of procalcitonin (PCT) as a marker for predicting dilating (grades III-V) vesicoureteral reflux (VUR) in young children with a first febrile urinary tract infection.. Children ≤2 years of age with a first febrile urinary tract infection were prospectively evaluated. Serum samples were tested for PCT at the time of admission to a tertiary hospital. All children underwent renal ultrasonography (US), Tc-dimercaptosuccinic acid renal scan, and voiding cystourethrography. The diagnostic characteristics of PCT test for acute pyelonephritis and dilating VUR were calculated.. Of 272 children analyzed (168 boys and 104 girls; median age, 5 months), 169 (62.1%) had acute pyelonephritis. There was VUR demonstrated in 97 (35.7%), including 70 (25.7%) with dilating VUR. The median PCT value was significantly higher in children with VUR than in those without (P < 0.001). Using a PCT cutoff value of ≥1.0 ng/mL, the sensitivity and negative predictive value for predicting dilating VUR were 94.3% and 95.4%, respectively, for PCT, and 97.1% and 97.8%, respectively, for the combined PCT and US studies, whereas the positive and negative likelihood ratios were 2.03 and 0.107, respectively, for PCT, and 1.72 and 0.067, respectively, for the combined studies. By multivariate analysis, high PCT values and abnormalities on US were independent predictors of dilating VUR.. PCT is useful for diagnosing acute pyelonephritis and predicting dilating VUR in young children with a first febrile urinary tract infection. A voiding cystourethrography is indicated only in children with high PCT values (≥1.0 ng/mL) and/or abnormalities found on a US.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child, Preschool; Cohort Studies; Female; Humans; Infant; Kidney; Male; Prospective Studies; Protein Precursors; Pyelonephritis; Radiography; Radiopharmaceuticals; Serum; Technetium Tc 99m Dimercaptosuccinic Acid; Ultrasonography; United States; Urinary Tract Infections; Vesico-Ureteral Reflux

Some patients with vesicoureteral reflux (VUR) develop reflux nephropathy (RN) and a number of them progress to chronic kidney disease (CKD). However, it is unclear to predict which patient will develop RN and/or CKD. The aim of this study is to evaluate the role of Interleukin-18 (IL-18), C-reactive protein (CRP) and procalcitonin (PCT) as an indicator of RN in VUR.. Ninety-three children aged 3.5-16 years with primary VUR were enrolled. Patients were divided into two groups according to the presence of renal scarring (RS). CRP, PCT, blood urea nitrogen (BUN), serum creatinine (Scr), urinary protein (Up), creatinine (Ucr) and microalbumin (Umalb), serum and urine IL-18 levels were determined during urinary tract infection (UTI) free episode.. BUN, Scr, Up/Ucr and Umalb/Ucr concentrations were higher whereas calculated creatinine clearance (Ccr) values were lower in RS (+) group compared to RS (-) group. CRP, PCT, serum and urine IL-18 levels and mean urine IL-18/Cr concentrations were similar in both groups. Serum and urine IL-18 levels did not differ according to the grade of VUR. No significant correlation was found between CRP, PCT and IL-18.. Proteinuria and microalbuminuria are valuable hallmarks of RN. CRP and PCT seem not to be reliable indicators of RN in VUR patients. Moreover, serum and urine IL-18 might not predict RN.

Topics: Adolescent; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Female; Humans; Interleukin-18; Kidney Diseases; Male; Prospective Studies; Protein Precursors; Vesico-Ureteral Reflux

Urinary tract infections (UTIs) are one of the most common sources of bacterial infections among young febrile children. Accurate diagnosis of acute pyelonephritis (APN) and vesico-ureteral reflux (VUR) are important because of their association with renal scarring, sometimes leading to long-term complications. However, the gold standard examinations are either a DMSA scan for APN and scarring, or cystography for VUR, but both present limitations (feasibility, pain, cost, etc.). Procalcitonin, a reliable marker of bacterial infections, was demonstrated to be a good predictor of renal parenchymal involvement in the acute phase and in late renal scars, as well as of high-grade VUR. These findings need further broad validations and impact studies before being implemented into daily practice. However, procalcitonin may play a role in the complex and still debated picture of which examination should be performed after UTI in children.

Topics: Adolescent; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Evidence-Based Medicine; Humans; Predictive Value of Tests; Protein Precursors; Pyelonephritis; Sensitivity and Specificity; Severity of Illness Index; Urinary Tract Infections; Vesico-Ureteral Reflux

To investigate the association between the procalcitonin (PCT) level during the first febrile urinary tract infection (UTI) in children and the presence of vesicoureteral reflux (VUR). VUR-associated UTI is among the primary causes of chronic renal failure in Turkey.. From March 2008 to November 2009, patients admitted with their first febrile UTI were included in the present prospective hospital-based study. The serum concentrations of C-reactive protein, complete blood count, and PCT were measured. All patients underwent renal ultrasonography and voiding cystourethrography.. Of the 66 patients who were diagnosed with UTI, 18 had VUR. The geometric mean of the PCT levels was significantly greater in the children with VUR than in those without (P = .006). After logistic regression adjustment, the association between the PCT levels and the presence of VUR remained significant (odds ratio 5.08, 95% confidence interval [CI] 1.43-18.02). A PCT level >0.56 ng/mL had 66.7% sensitivity (95% CI 41-86.6) and 77.1% specificity (95% CI 62.7-88) for diagnosing VUR. The area under the receiver operating characteristic curve for PCT was 0.715 (95% CI, 0.56-0.86, P = .007), and the area under the curve for C-reactive protein was 0.723 (95% CI 0.58-0.86, P = .006).. A PCT-guided strategy could help in detecting patients with VUR. Large cohort studies are needed to define an accurate cutoff value for children who are at risk of VUR, which increases the risk of renal damage and subsequent scarring.

Topics: Adolescent; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Comorbidity; Female; Humans; Infant; Logistic Models; Male; Prospective Studies; Protein Precursors; ROC Curve; Urinary Tract Infections; Vesico-Ureteral Reflux

To compare two first febrile urinary tract infection (UTI) management protocols with regards to the diagnosis of high-grade vesicoureteral reflux (VUR) and cost.. This study compared two cohorts of children under 16 years of age, admitted for a first episode of febrile UTI. The first group (in 2005) was managed according to previous recommendations (IV treatment and cystography performed for all children under 3 years of age). The second group (in 2006) was managed according to age and procalcitonin level. High-grade VUR frequency, UTI recurrence, hospitalization rate, and cost were compared between the two cohorts.. A total of 225 children were included in 2005 and 116 in 2006. High-grade VUR was found in 6.2 and 9.5% of the patients in 2005 and 2006, respectively (P=0.274). There was no statistically significant difference in the UTI recurrence rate between the two cohorts (5.3% in 2005 and 8.6% in 2006; P=0.237). The mean cost of an episode of febrile UTI was not significantly different in 2005 and 2006 (€2235 in 2005, €2256 in 2006; P=0.902), but was lower for children older than 6 months in 2006 (€1292 versus €1882 in 2005; P=0.0042).. Our management protocol for a first febrile UTI episode in children based on procalcitonin levels seems to be suitable for the diagnosis of high-grade VUR. The hospitalization rate and the mean cost of management for children older than 6 months of age was significantly reduced in 2006. The management guidelines for a first occurrence of febrile UTI in children should be reconsidered.

Topics: Adolescent; Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Cohort Studies; Female; Fever; France; Humans; Infant; Inpatients; Length of Stay; Male; Practice Guidelines as Topic; Predictive Value of Tests; Protein Precursors; Sensitivity and Specificity; Treatment Outcome; Urinary Tract Infections; Vesico-Ureteral Reflux

Predicting vesico-ureteral reflux (VUR) ≥3 at the time of the first urinary tract infection (UTI) would make it possible to restrict cystography to high-risk children. We previously derived the following clinical decision rule for that purpose: cystography should be performed in cases with ureteral dilation and a serum procalcitonin level ≥0.17 ng/mL, or without ureteral dilatation when the serum procalcitonin level ≥0.63 ng/mL. The rule yielded a 86% sensitivity with a 46% specificity. We aimed to test its reproducibility.. A secondary analysis of prospective series of children with a first UTI. The rule was applied, and predictive ability was calculated.. The study included 413 patients (157 boys, VUR ≥3 in 11%) from eight centers in five countries. The rule offered a 46% specificity (95% CI, 41-52), not different from the one in the derivation study. However, the sensitivity significantly decreased to 64% (95%CI, 50-76), leading to a difference of 20% (95%CI, 17-36). In all, 16 (34%) patients among the 47 with VUR ≥3 were misdiagnosed by the rule. This lack of reproducibility might result primarily from a difference between derivation and validation populations regarding inflammatory parameters (CRP, PCT); the validation set samples may have been collected earlier than for the derivation one.. The rule built to predict VUR ≥3 had a stable specificity (ie. 46%), but a decreased sensitivity (ie. 64%) because of the time variability of PCT measurement. Some refinement may be warranted.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Child; Decision Making; Female; Humans; Male; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Urinary Tract Infections; Vesico-Ureteral Reflux

A first febrile urinary tract infection leads to the diagnosis of vesicoureteral reflux in 20% to 40% of children. Systematic voiding cystourethrography then is recommended. However, for 60% to 80% of the children, voiding cystourethrography is a posteriori normal. Moreover, it is irradiating, painful, and expensive. Thus, selective approaches are needed. Because procalcitonin has been shown to be associated with severe pyelonephritis and renal scars, which are correlated to vesicoureteral reflux, we analyzed its relationship with vesicoureteral reflux.. A retrospective hospital-based cohort study included all children who were 1 month to 4 years of age and had a first febrile urinary tract infection. Univariate and multivariate analyses were performed.. Among 136 patients included, 25% had vesicoureteral reflux. The median procalcitonin concentration was significantly higher in children with reflux than in those without (1.2 vs 0.6 ng/mL). High procalcitonin (> or =0.5 ng/mL) was associated with reflux (odds ratio [OR]: 4.6; 95% confidence interval [CI]: 1.6-16.2). After logistic-regression adjustment for all potential confounders, the association remained significant (OR: 4.9; 95% CI: 1.7-14.0). The relationship was stronger for high-grade (> or =3) reflux (OR: 8.7; 95% CI: 1.2-382) than low-grade reflux (OR: 3.6; 95% CI: 1.1-15.3). High procalcitonin sensitivities were 85% (95% CI: 70-94) and 92% (95% CI: 65-99) for all-grade and high-grade reflux, respectively, with 44% specificity (95% CI: 35-54).. High procalcitonin is a strong and independent predictor of vesicoureteral reflux and could be used to identify low-risk patients to avoid unnecessary voiding cystourethrography.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child, Preschool; Cohort Studies; Female; Fever; Humans; Infant; Infant, Newborn; Male; Protein Precursors; Retrospective Studies; Sensitivity and Specificity; Urinary Tract Infections; Vesico-Ureteral Reflux

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child, Preschool; False Positive Reactions; Humans; Protein Precursors; Sensitivity and Specificity; Specimen Handling; Urinary Tract Infections; Urine; Vesico-Ureteral Reflux