Corticosteroids to prevent kidney scarring in children with a febrile urinary tract infection: a randomized trial.
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ABSTRACT: Background
To evaluate the efficacy of adjuvant systemic corticosteroids in reducing kidney scarring. A previous study suggested that use of adjuvant systemic corticosteroids reduces kidney scarring in children radiologically confirmed to have extensive pyelonephritis. Efficacy of corticosteroids for children with febrile urinary tract infection (UTI) has not been studied.Methods
Children aged 2 months to 6 years with their first febrile UTI were randomized to corticosteroids or placebo for 3 days (both arms received antimicrobial therapy); kidney scarring was assessed using 99mTc-dimercaptosuccinic acid kidney scan 5-24 months after the initial UTI.Results
We randomized 546 children of which 385 had a UTI and 254 had outcome kidney scans (instead of the 320 planned). Rates of kidney scarring were 9.8% (12/123) and 16.8% (22/131) in the corticosteroid and placebo groups, respectively (p = 0.16), corresponding to an absolute risk reduction of 5.9% (95% confidence interval: - 2.2, 14.1).Conclusion
While children randomized to adjuvant corticosteroids tended to develop fewer kidney scars than children who were randomized to receive placebo, a statistically significant difference was not achieved. However, the study was limited by not reaching its intended sample size.Clinical trial registration
Clinicaltrials.gov , NCT01391793, Registered 7/12/2011 Graphical abstract.
SUBMITTER: Shaikh N
PROVIDER: S-EPMC7529851 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThis study aimed to evaluate the effect of oral dexamethasone in reducing kidney scars in infants with a first febrile urinary tract infection (UTI).MethodsChildren aged between 2 and 24 months with their first presumed UTI, at high risk for kidney scarring based on procalcitonin levels (≥1 ng/mL), were randomly assigned to receive dexamethasone in addition to routine care or routine care only. Kidney scars were identified by kidney scan at 6 months after initial UTI. Projections of enrollment and follow-up completion showed that the intended sample size could not be reached before funding and time to complete the study ran out. An amendment to the protocol was approved to conduct a Bayesian analysis.ResultsWe randomized 48 children, of whom 42 had a UTI and 18 had outcome kidney scans (instead of 128 planned). Kidney scars were found in 0/7 and 2/11 patients in the treatment and control groups respectively. The probability that dexamethasone could prevent kidney scarring was 99% in the setting of an informative prior probability distribution (which fully incorporated in the final inference the information on treatment effect provided by previous studies) and 98% in the low-informative scenario (which discounted the prior literature information by 50%). The probabilities that dexamethasone could reduce kidney scar formation by up to 20% were 61% and 53% in the informative and low-informative scenario, respectively.ConclusionsDexamethasone is highly likely to reduce kidney scarring, with a more than 50% probability to reduce kidney scars by up to 20%.Trial registration numberEudraCT number: 2013-000388-10; registered in 2013 (prospectively registered) A higher resolution version of the Graphical abstract is available as Supplementary information.
| S-EPMC8497283 | biostudies-literature
Project description:To identify risk factors for recurrent urinary tract infection (UTI) and renal scarring in children who have had 1 or 2 febrile or symptomatic UTIs and received no antimicrobial prophylaxis.This 2-year, multisite prospective cohort study included 305 children aged 2 to 71 months with vesicoureteral reflux (VUR) receiving placebo in the RIVUR (Randomized Intervention for Vesicoureteral Reflux) study and 195 children with no VUR observed in the CUTIE (Careful Urinary Tract Infection Evaluation) study. Primary exposure was presence of VUR; secondary exposures included bladder and bowel dysfunction (BBD), age, and race. Outcomes were recurrent febrile or symptomatic urinary tract infection (F/SUTI) and renal scarring.Children with VUR had higher 2-year rates of recurrent F/SUTI (Kaplan-Meier estimate 25.4% compared with 17.3% for VUR and no VUR, respectively). Other factors associated with recurrent F/SUTI included presence of BBD at baseline (adjusted hazard ratio: 2.07 [95% confidence interval (CI): 1.09-3.93]) and presence of renal scarring on the baseline (99m)Tc-labeled dimercaptosuccinic acid scan (adjusted hazard ratio: 2.88 [95% CI: 1.22-6.80]). Children with BBD and any degree of VUR had the highest risk of recurrent F/SUTI (56%). At the end of the 2-year follow-up period, 8 (5.6%) children in the no VUR group and 24 (10.2%) in the VUR group had renal scars, but the difference was not statistically significant (adjusted odds ratio: 2.05 [95% CI: 0.86-4.87]).VUR and BBD are risk factors for recurrent UTI, especially when they appear in combination. Strategies for preventing recurrent UTI include antimicrobial prophylaxis and treatment of BBD.
| S-EPMC4485012 | biostudies-literature
Project description:BackgroundAn association between bladder-bowel dysfunction (BBD) and urinary tract infection (UTI) is well-known. However, a question less explored is whether children with UTI early in life also have increased prevalence of BBD after they are toilet-trained. In this study, consecutively selected children with pyelonephritis during their first year of life were assessed for BBD at pre-school age.MethodsNinety-two children (51 boys) hospitalized due to pyelonephritis during their first year of life were assessed for BBD at median age 5.4 years. A validated BBD questionnaire, along with urine flow and residual volume measurements, was used for diagnosing BBD. During follow-up, the group was well-characterized regarding renal status, vesicoureteral reflux (VUR), and recurrent UTI.ResultsBBD was diagnosed in 35/92 (38%), of which the majority was sub-diagnosed with dysfunctional voiding (DV). There was a strong association between BBD and recurrent UTI during follow-up (p < 0.0001), but only a slight association with VUR status at presentation. Nevertheless, in the group with both BBD and VUR, recurrent UTI was four times higher (12/13, 92%) than in children who had neither VUR nor BBD (23%), (p = 0.0008). BBD was also associated with kidney damage (p = 0.017).ConclusionIn children with pyelonephritis during the first year of life, 38% had BBD at pre-school age, regardless of whether they had VUR or not. The study shows an important association between BBD and recurrent UTI, so an assessment of BBD is therefore recommended for pre-school children with UTI, especially when they have history of pyelonephritis during infancy.
| S-EPMC8084797 | biostudies-literature
Project description:BackgroundAlthough urinary tract infection (UTI) resolves with prompt treatment in a majority of children, some children, especially those aged less than 5 years, also develop renal parenchymal scarring (RPS). RPS causes high blood pressure that may lead to severe chronic kidney disease and end-stage renal disease (ESRD). Although the risk of UTI is higher in white children than in black children, it is unknown whether RPS is more common in white children than in black children as data are scarce in this regard. A common genetic predisposition to kidney disease in African Americans and the sub-Saharan African blacks is the possession of apolipoprotein L1 (APOL1). APOL1 risk variants regulate the production of APOL1. APOL1 circulates in the blood, and it is also found in the kidney tissue. While circulating, APOL1 kills the trypanosome parasites; an increased APOL1 in kidney tissues, under the right environmental conditions, can also result in the death of kidney tissue (vascular endothelium, the podocytes, proximal tubules, and arterial cells), which, ultimately, is replaced by fibrous tissue. APOL1 may influence the development of RPS, as evidence affirms that its expression is increased in kidney tissue following UTI caused by bacteria. Thus, UTI may be a putative environmental risk factor responsible for APOL1-induced kidney injury.ObjectiveThe aim of this proposal was to outline a study that seeks to determine if the possession of two copies of either G1 or G2 APOL1 variant increases the risk of having RPS, 6 months following a febrile UTI among Nigerian under-five children.MethodsThis case-control association study seeks to determine whether the risk of RPS from febrile UTI is conditional on having 2 APOL1 risk alleles (either G1 or G2). Cases will be children with a confirmed RPS following a febrile UTI. Controls will be age-, gender-, and ethnic-matched children with a febrile UTI but without RPS. Children with vesicoureteral reflux and other congenital anomalies of the urinary tract are to be excluded. Association between predictor variables (ethnicity, APOL1 G1 or G2, and others) and RPS will be tested at bivariate logistic regression analyses. Predictors that attained significance at a P value of ˂.05 will be considered for multiple logistic regressions. Likelihood-based tests will be used for hypothesis testing. Estimation will be done for the effect size for each of the APOL1 haplotypes using a generalized linear model.ResultsThe study is expected to last for 3 years.ConclusionsThe study is contingent on having a platform for undergoing a research-based PhD program in any willing university in Europe or elsewhere. The findings of this study will be used to improve the care of African children who may develop RPS following febrile UTI.Registered report identifierRR1-10.2196/9514.
| S-EPMC6024104 | biostudies-literature
Project description:PurposeRecent studies have demonstrated trends of decreasing voiding cystourethrogram utilization rates and delayed vesicoureteral reflux diagnosis in some children. It is possible that such delays could lead to more children sustaining repeated episodes of febrile urinary tract infection, and potential kidney injury, prior to diagnosis and treatment.Materials and methodsUsing single institutional, cross-sectional cohorts of patients in 2 time periods (2005 and 2015), we compared clinical presentation and renal outcomes among patients 13 years and younger with history of febrile urinary tract infection presenting for initial voiding cystourethrogram. Outcomes included 1) recurrent urinary tract infection, 2) presence of vesicoureteral reflux, 3) grade of vesicoureteral reflux, and 4) renal scarring. Associations between year of presentation and outcomes of recurrent urinary tract infection and vesicoureteral reflux diagnosis were evaluated using multivariable logistic regression models. For the outcome of renal scarring, a logistic regression model was fitted for propensity score matched cohorts.ResultsCompared to children presenting in 2005, those in 2015 had 3 times the odds of recurrent urinary tract infection (OR 3.01, 95% CI 2.18-4.16, p <0.0001). Time period was not associated with the odds of vesicoureteral reflux (OR 0.98, 95% CI 0.77-1.23, p=0.85). Those in 2015 were more likely to present with vesicoureteral reflux grade >3 (OR 2.22, 95% CI 1.13-4.34, p=0.02) but not vesicoureteral reflux grade >2 (OR 1.11, 95% CI 0.74-1.67, p=0.60). Renal scarring was more common among children presenting in 2015 (OR 2.9, 95% CI 1.03-8.20, p=0.04).ConclusionsCompared to 2005, children presenting in 2015 for post-urinary tract infection voiding cystourethrogram have increased likelihood of recurrent urinary tract infection and renal scarring, despite similar likelihood of vesicoureteral reflux diagnosis.
| S-EPMC8106649 | biostudies-literature
Project description:IntroductionThe clinical features of UTI in young children may not localize to the urinary tract and closely resemble other febrile illnesses. In malaria endemic areas, a child presenting with fever is often treated presumptively for malaria without investigation for UTI. Delayed or inadequate treatment of UTI increases the risk of bacteremia and renal scarring in young children and subsequently complications as hypertension and end stage renal disease in adulthood.MethodsA cross-sectional study was carried out in a hospital in western Kenya. Inpatients and outpatients 2 months to five years with axillary temperature ≥37.5°C and no antibiotic use in the previous week were enrolled between September 2012 and April 2013. Urine dipstick tests, microscopy, and cultures were done and susceptibility patterns to commonly prescribed antibiotics established. UTI was defined as presence of pyuria (a positive urine dipstick or microscopy test) plus a positive urine culture.ResultsA total of 260 subjects were recruited; 45.8% were female and the median age was 25months (IQR: 13, 43.5). The overall prevalence of UTI was 11.9%. Inpatients had a higher prevalence compared to outpatients (17.9% v 7.8%, p = 0.027). UTI co-existed with malaria but the association was not significant (OR 0.80, p = 0.570). The most common organisms isolated were Escherichia coli (64.5%) and Staphylococcus aureus (12.9%) and were sensitive to ciproflaxin, cefuroxime, ceftriaxone, gentamycin and nitrofurantoin but largely resistant to more commonly used antibiotics such as ampicillin (0%), amoxicillin (16.7%), cotrimoxazole (16.7%) and amoxicillin-clavulinate (25%).ConclusionOur study demonstrates UTI contributes significantly to the burden of febrile illness in young children and often co-exists with other infections. Multi-drug resistant organisms are common therefore choice of antimicrobial therapy should be based on local sensitivity pattern.
| S-EPMC5360311 | biostudies-literature
Project description:Urinary tract infections are the initial manifestation in 30% of urinary tract malformations. Identifying these patients, who could benefit from a specific treatment, is still challenging. Hyponatremia during urinary tract infection has been proposed as a urinary tract malformation marker. We evaluate the prevalence of hyponatremia during febrile urinary tract infections and its association with subjacent urinary tract malformations. We performed a retrospective study of healthy patients under 16 years, diagnosed with a first episode of febrile urinary tract infection, who had undergone blood testing in the acute episode and at least one renal ultrasound during follow-up (January 2014-November 2020). Hyponatremia was defined as (serum sodium ≤ 130 mEq/L). According to imaging findings, we classified patients into three groups: normal kidney ultrasound, mild pelviectasis, and significant urinary tract malformation. We performed logistic regression models to identify independent risk factors for urinary tract malformation and mild pelviectasis. We included 492 patients and 2.8% presented hyponatremia. We identified normal ultrasound in 77%, mild pelviectasis in 10.8%, and urinary tract malformation in 12% of patients. We found an association between mild pelviectasis and hyponatremia [OR 6.6 (CI95% 1.6-26.6)]. However, we found no association between hyponatremia and urinary tract malformation. The parameters that were associated with malformations were presenting a non-E. coli infection, C-reactive-protein levels over 80 mg/L, and bacteremia.ConclusionHyponatremia during the first episode of febrile urinary tract infection is present in 2.8% of patients and is associated with mild pelviectasis in imaging. However, hyponatremia does not indicate a greater need for complementary tests to screen for urinary tract malformations.What is known• Urinary tract infection is the first manifestation in 30% of children with urinary tract malformation. • Hyponatremia could be a marker to identify these children and guide the imaging approach.What is new• Around 12% of children with a first episode of febrile urinary tract infection have a urinary tract malformation. • Non-E. coli infection, C-reactive protein levels over 80 mg/L, and bacteremia are markers for malformations to guide diagnostic imaging tests, but hyponatremia (Na ≤ 130 mEq/l) is not a reliable marker.
| S-EPMC10640435 | biostudies-literature
Project description:ObjectiveTo identify risk factors for febrile recurrence of urinary tract infections (UTIs) in children with a history of UTI.Study designWe included 500 children aged 2-72 months with a history of UTI who were followed prospectively for approximately 2 years in the context of 2 previously conducted studies (Randomized Intervention for Children with Vesicoureteral Reflux and Careful Urinary Tract Infection Evaluation). We identified significant risk factors for febrile recurrences among children not receiving antimicrobial prophylaxis using univariate and multivariate logistic regression.ResultOn univariate analysis, non-Black race, febrile index UTI, bowel-bladder dysfunction, grade IV vesicoureteral reflux, renal scarring at baseline, and renal-bladder ultrasound abnormalities were associated with febrile recurrence. On multivariate analysis, the following variables independently increased the odds of febrile recurrences (OR; 95% CI): non-Black race (7.1; 1.5-127.9), bowel-bladder dysfunction (2.6; 1.1-5.3), febrile index UTI (2.5; 1.1-6.9), abnormalities on renal-bladder ultrasound scan (2.6; 1.2-5.6), grade IV vesicoureteral reflux (3.9; 1.4-10.5), and renal scarring at baseline (4.7; 1.2-19.1).ConclusionsNon-Black race and grade IV vesicoureteral reflux increased the odds of febrile recurrence of UTI. Although our findings should stimulate other studies to further explore the relationship between race and UTIs, given that the link between race and UTI recurrence is unclear, race should not be used to make decisions regarding management of children with a UTI.
| S-EPMC8960327 | biostudies-literature
Project description:This study aimed to investigate the predictive factors of concomitant bacteremia occurring in febrile infants who initially presented with pyuria and fever, and were subsequently diagnosed with culture-proven urinary tract infection (UTI). We conducted a retrospective cohort study for January 2010-October 2018 that included infants younger than six months with febrile UTI at a tertiary hospital. The study included 463 patients, of whom 34 had a concomitant bacteremic UTI. Compared to those in the non-bacteremic urinary tract infection (UTI) group, the bacteremic UTI group had a lower mean age; higher levels of C-reactive protein (CRP), delta neutrophil index (DNI, reflects the fraction of immature granulocytes) and blood urea nitrogen (BUN); lower levels of hemoglobin (Hb) and albumin; and a lower platelet count. Vesicoureteral reflux (VUR) was detected nearly twice as often in patients with bacteremic UTI compared to those with non-bacteremic UTI (59.3% vs. 30.6%; P = 0.003). Univariate logistic analyses showed that age ≤90 days; higher DNI, CRP, and creatinine levels; lower Hb and albumin levels; and the presence of VUR were predictors for bacteremic UTI. On multivariate logistic regression analysis, age ≤90 days, higher DNI and CRP levels, and the presence of VUR were independent predictors of bacteremic UTI. The area under the receiver operating characteristic curve of the multivariate model was 0.859 (95% CI, 0.779-0.939; P < 0.001). Age ≤90 days, higher DNI and CRP values may help predict bacteremia of febrile infants younger than 6 months with UTI. Vesicoureteral reflux imaging is also recommended in infants with bacteremic UTI to evaluate VUR.
| S-EPMC7066144 | biostudies-literature
Project description:There are currently no available data on the relationship between sonographic temporary nephromegaly in children during their first febrile urinary tract infection (fUTI) and recurrent fUTI. For this analysis, a multicenter retrospective cohort study of 343 children who underwent renal ultrasound during their first fUTI was conducted between 2013 and 2020. Sonographic temporary nephromegaly was defined as increased renal length during the initial fUTI, followed by normal renal length after antibiotic treatment. Compared with children without sonographic temporary nephromegaly (n = 307), the duration of fever and intravenous antibiotics was significantly longer, and C-reactive protein, creatinine, and the proportion of children who had recurrent fUTI were significantly higher, in those with sonographic temporary nephromegaly (n = 36). In an additional analysis of 100 patients who received voiding cystourethrography, a logistic regression model confirmed that the odds of vesicoureteral reflux (VUR) were significantly higher in children with temporary nephromegaly or those who experienced fUTI recurrence. In nine out of 16 children with VUR who had temporary nephromegaly, the reason for receiving voiding cystourethrography was recurrent fUTI. Our results suggest that sonographic temporary nephromegaly during an initial fUTI is predictive for recurrence and VUR, and that in children with temporary nephromegaly, VUR may be detectable before fUTI recurrence.
| S-EPMC11335903 | biostudies-literature