Subsequent Renal Scarring Research Articles

Prediction Model for Urinary Tract Infection in Pediatric Urological Surgery Patients

BackgroundUrinary tract infection (UTI) is a common complication in pediatric urological surgery patients and is associated with long-term sequelae, including subsequent recurrent infections and renal scarring. In this study, we aimed to explore the risk factors for UTI in pediatric urological surgery patients and construct a predictive model for UTI.Materials and MethodsA total of 2,235 pediatric patients who underwent urological surgery at a tertiary hospital between February 2019 and January 2020 were included. A multivariate logistic regression model was applied to identify the predictive factors, and a predictive model was constructed using a receiver operating characteristic curve. A multifactorial predictive model was used to categorize the risk of UTI based on the weight of the evidence.ResultsA total of 341 patients with UTI were identified, which corresponded to a prevalence of 15.26% in pediatric urological surgery patients. Multivariate analysis identified six significant risk factors for UTI, including age <12.0 months, upper urinary tract disease, not using an indwelling drainage tube, hospital stay ≥10 days, administration of two or more types of antibiotics, and stent implantation. A combination of the aforementioned factors produced an area under the curve value of 88.37% for preventing UTI in pediatric urological surgery patients. A multifactorial predictive model was created based on the combination of these factors.ConclusionsThe constructed multifactorial model could predict UTI risk in pediatric urological surgery patients with a relatively high predictive value.

Serum soluble ST2 as a marker of renal scar in pediatric upper urinary tract infection

Background and objectivesUpper urinary tract infection is the most common serious bacterial infection in childhood. Patients with upper urinary tract infection have a risk for renal scarring with subsequent complications including hypertension, proteinuria, and progressive renal failure. However, the predictive biomarkers of renal scarring in children with upper urinary tract infection are still unknown. In this study, we evaluated whether soluble ST2 levels can be biomarkers of subsequent renal scarring in patients with upper urinary tract infection. Design, setting, participants, and measurementsWe retrospectively studied pediatric patients with upper urinary tract infection at a tertiary center. Twenty-eight children had an upper urinary tract infection with (n = 14) and without (n = 14) renal scarring and underwent 99mtechnetium dimercaptosuccinic acid imaging. In addition, 13 control subjects were enrolled. The clinical data and serum cytokine levels, including soluble ST2 levels, were compared between those with and without renal scars. ResultsSerum soluble ST2 levels were significantly higher in the scar group than in the non-scar group, whereas there was no difference in the levels of serum interferon-γ, interleukin-6, interleukin-10, soluble tumor necrosis factor receptor 1, and transforming growth factor-β between the scar and non-scar groups. The area under the curve for differentiating between the non-scar and scar groups on the basis of measurements of serum soluble ST2 was 0.79, with a sensitivity and specificity of 92.9% and 64.3%, respectively. ConclusionThese results suggest that serum soluble ST2 levels on admission could be a useful biomarker of subsequent renal scarring in pediatric patients with upper urinary tract infection.

Study of 99 m-Tc DMSA (Dimercaptosuccinicacid) Scintigraphy in children with urinary tract infection

Introduction: DMSA scan is superior to ultrasonography in detecting cortical scars, although the later identifies dilatation of the collecting systems and renal swelling. This study was conducted to know the role of 99m- Tc Dimercaptosuccinic acids (DMSA) scan in children with UTI, its role in the early detection of renal scar. Materials and Methods: A study was conducted among 125 children at Dr. B.R. Ambedkar Medical College, Bangalore from August 2015- October 2017. The study group included both inpatient and outpatient children with urinary tract infection. The patients with culture positive urinary tract infections during first and recurrent attacks were studied and followed from 3 months to 2 years. On follow- up 99m -Tc DMSA scan was conducted, if needed USG abdomen and MCU scan were conducted. Results: 44% of the children showed abnormal features both by DMSA scan and USGand 21.6% of the children had normal scan but found to have abnormality in DMSA scan. On follow- up of the children, it was noticed that in 56% of the DMSA scan was normal, in 6% of children who initially had renal scar, on follow up did not have renal scar. 24% of the children persisted to have renal scar on follow up and 12% who initially had normal DMSA scan, on follow up had scar. In that 12 children with renal scar, all the children had VUR grade 4-5. Conclusion: 99m-Tc DMSA scintigraphy is the gold standard for early identification and evaluation of acute renal inflammation and subsequent renal scarring. This study recommends both renal ultrasound scanning and 99m-Tc DMSA scintigraphy to be routinely performed in infants and children with a first febrile UTI because ultrasonography alone as low sensitivity for the detection of renal cortical abnormalities.

Assessment of renal parenchymal changes using isotope renography for genitourinary indications in pediatric age group-a study of 47 cases

Background: With the introduction of isotope renography using DMSA (Dimercaptosuccinic acid), more stress than ever has been put on the evaluation of renal parenchyma in a morphologically normal but injured kidney. Objective: To study the pattern of renal dysfunction and anomalies noted after isotope renography using DMSA. Materials and methods: A retrospective study was conducted at department of Paediatrics of Amala Institute of Medical Sciences, Thrissur after evaluating the hospital records involving children undergoing isotope renography using DMSA (IRDMSA) for genitourinary indications between August 1st 2012 and August 1st 2013. Results: The common indications for IRDMSA were found to be urinary tract infections (UTI) (61.7%), multicystic dysplastic kidneys (MCDK) (12.7%), posterior urethral valve (PUV) (6.3%) and unilateral hydronephrosis (6.3%). Among the UTI group, 10.7% had the evidence of bilateral renal scarring and 42.8% unilateral renal scarring. Only 32.1% had bilaterally normal kidneys. Analysis of 7 cases with significantly reduced differential function (DF< 30/70) showed associated vesicoureteral reflux (VUR) in 100% cases. A male predominance was noticed even though only one case had posterior urethral valve. Right kidney was found to be more susceptible than the left. A study of the scar topography showed majority to be localized to the upper pole and superolateral border. 100% of the MCDKs were found to be non-functional and was not visualized in the renogram. Conclusion: IRDMSA is a reliable imaging modality in the follow up of acute pyelonephritis in children, detecting structural abnormalities and also for identifying kidneys in children at risk for subsequent renal scarring.

Labial adhesion and urinary tract problems: The importance of genital examination

Urinary tract infection (UTI) is a common bacterial illness in children. Delay in the treatment of UTI may lead to acute renal parenchymal damage and subsequent renal scarring. It is well established that several risk factors increase the tendency for UTI - one being labial adhesion (LA). The purpose of this study was to emphasize the importance of genital examination in girls with nephrourologic symptoms, particularly UTIs, in order to detect LA. Data were collected from the files of 46 girls with LA, including: the girl's age, thickness of LA, any recurrence and treatment options of LA, and the reason for admission to hospital. The LAs were grouped in terms of thickness as thin, moderate and dense, and also partial or complete. The average age of the girls at the first visit was 51.9 ± 37.57 months (min-max: 3.5-157 months). Twenty-seven (58.7%) of the girls had history of recurrent UTI. There was a marked association between the presence of UTI and the type of adhesions. The percentages of UTIs in girls with complete and partial LA were 84.0% and 28.6%, respectively (P < 0.05). The percentages of UTIs in girls with thick and thin LA were 100% and 44.1%, respectively (P < 0.05). None of the girls' primary care physicians or pediatricians recognized LA at the time of a periodic health examination. In the present study, girls with complete and thick LA had a greater tendency towards having UTIs than those with partial and thin LA, respectively. After treatment of LA, the UTIs did not recur in any girls. None of the girls in this study had undergone a previous genital examination. Therefore, this study suggests that physicians do not often perform genital examinations. Limitations of this study were the small sample size and the short follow-up period. In addition, although all of the girls were examined by the same physician, the thickness of the membrane is subjective and solely depends on the physician's experience. This study showed that although genital examination is a routine part of a physical examination, it is not always performed. Therefore, it is recommend that genital examination should be performed in girls with nephrourologic complaints, particularly for UTI. By timeously determining the presence of LA, many unnecessary and invasive investigations could be avoided in these children.

The diagnosis of febrile urinary tract infection in children may be facilitated by urinary biomarkers.

We prospectively assessed the feasibility of two urinary markers of renal injury as potential diagnostic tests for acute febrile urinary tract infection (UTI) and subsequent renal scarring. The patient cohort comprised children aged 0 to 4 years who visited the emergency room. The children were divided into three groups, namely, a febrile UTI (fUTI), febrile control (FC) and a non-febrile control (NFC) group, respectively, which were matched for sex and age. An enzyme-linked immunosorbent assay for neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) was performed on urine collected from each child. The urine levels of both markers were compared between the three groups, and the diagnostic accuracy was determined based on the area under the receiver-operator characteristic curve (AUC). In the fUTI group, the predictability of subsequent renal scarring was assessed by associating urinary levels with dimercaptosuccinic acid findings 6 months after an UTI episode. Significantly elevated levels of urinary NGAL and KIM-1 were observed in the fUTI group, as well as with increased urine esterase, serum C-reactive protein, and pyuria. The AUC was 72 % for KIM-1 and 96 % for NGAL. The AUC of KIM-1 for the prediction of scarring was 71 % (p < 0.05). The diagnosis of febrile UTI and the prediction of subsequent scarring may be facilitated by assaying urine biomarkers with acceptable accuracy.

Urinary concentration of cytokines in children with acute pyelonephritis

Urinary tract infection (UTI) is a common bacterial infection among infants and children. Predicting which children with upper UTI will develop long-term sequelae remains difficult. We aimed at evaluating the predictive value of urine concentrations of interleukin-6 (UIL-6) and interleukin-8 (UIL-8) in subsequent renal scarring. In the current observational prospective study, urine samples for UIL-6 and UIL-8 were obtained from two groups: 31 children with first episode of febrile UTI and 22 febrile children of other origin. UIL-6 and UIL-8 were increased in children with febrile UTI, compared to children with fever of other origin [median and range (picograms per milliliter): (1) UIL-6, 74.46 (0-168) vs. 10.51 (0-47.50), respectively, p = 0.0001; (2) UIL-8, 2,660.38 (0-13,801) vs. 0, respectively, p = 0.0001]. Renal scarring was found in 5/31 (16 %) children with acute pyelonephritis. Initial median UIL-8 values were significantly higher in children with later renal scarring than in those without renal scarring [median and range (picograms per milliliter): 6,163 (2,021-13,801) vs. 1,490.5 (0-5,737), respectively, p = 0.018]. In conclusion, UIL-8 might serve as a predictive biomarker for renal scarring after an acute episode of pyelonephritis. Since UIL-8 emerges as a renal-specific diagnostic and prognostic marker, it may be suitable as a selective screening tool for children with febrile UTI.

Incidence of Abnormal Imaging and Recurrent Pyelonephritis after First Febrile Urinary Tract Infection in Children 2 to 24 Months Old

The AAP (American Academy of Pediatrics) no longer recommends voiding cystourethrogram in children 2 to 24 months old who present with a first urinary tract infection if renal-bladder ultrasound is normal. We identified factors associated with abnormal imaging and recurrent pyelonephritis in this population. We retrospectively evaluated children diagnosed with a first episode of pyelonephritis at age 2 to 24 months using de-identified electronic medical record data from an institutional database. Data included age at first urinary tract infection, gender, race/ethnicity, need for hospitalization, intravenous antibiotic use, history of abnormal prenatal ultrasound, renal-bladder ultrasound and voiding cystourethrogram results, urinary tract infection recurrence and surgical intervention. Risk factors for abnormal imaging and urinary tract infection recurrence were analyzed by univariate logistic regression, the chi-square test and survival analysis. We identified 174 patients. Of the 154 renal-bladder ultrasounds performed 59 (38%) were abnormal. Abnormal prenatal ultrasound (p = 0.01) and the need for hospitalization (p = 0.02) predicted abnormal renal-bladder ultrasound. Of the 95 patients with normal renal-bladder ultrasound 84 underwent voiding cystourethrogram. Vesicoureteral reflux was more likely in patients who were white (p = 0.003), female (p = 0.02) and older (p = 0.04). Despite normal renal-bladder ultrasound, 23 of 84 patients (24%) had dilating vesicoureteral reflux. Of the 95 patients with normal renal-bladder ultrasound 14 (15%) had recurrent pyelonephritis and 7 (7%) went on to surgical intervention. Despite normal renal-bladder ultrasound after a first pyelonephritis episode, a child may still have vesicoureteral reflux, recurrent pyelonephritis and the need for surgical intervention. If voiding cystourethrogram is deferred, parents should be counseled on these risks.

The Role of Procalcitonin for Acute Pyelonephritis and Subsequent Renal Scarring in Infants and Young Children

The Role of Procalcitonin for Acute Pyelonephritis and Subsequent Renal Scarring in Infants and Young Children

The Role of Procalcitonin for Acute Pyelonephritis and Subsequent Renal Scarring in Infants and Young Children

We assessed the usefulness of procalcitonin as a biological marker in diagnosing acute pyelonephritis and for predicting subsequent renal scarring in young children with a first febrile urinary tract infection. Children 2 years old or younger with a first febrile urinary tract infection were prospectively studied. Renal parenchymal involvement was assessed by (99m)Tc-dimercaptosuccinic acid scan within 5 days of admission and after 6 months. Serum samples from all patients were tested for procalcitonin, C-reactive protein and white blood cell count measurements. The 112 enrolled patients (age range 24 days to 24 months old) were divided into acute pyelonephritis (76) and lower urinary tract infection (36) groups according to the results of (99m)Tc-dimercaptosuccinic acid scans. Median values of procalcitonin, C-reactive protein and white blood cell count at hospitalization were significantly higher in patients with acute pyelonephritis than in those with lower urinary tract infection. The area under receiver operating characteristic curves showed that procalcitonin was superior to C-reactive protein and white blood cell count as a marker for diagnosing acute pyelonephritis. Initial and post-antibiotic treatment procalcitonin values were significantly higher in children with renal scarring than in those without scarring (p <0.001). Procalcitonin values at hospitalization and after treatment were independent predictors of later renal scarring on logistic regression analysis. Our results indicate the superior diagnostic accuracy of procalcitonin for predicting acute pyelonephritis in children 2 years old or younger. Higher initial and posttreatment procalcitonin values are independent risk factors for later renal scarring.

Prevention of chronic kidney disease in spina bifida

The prevalence of progressive chronic kidney disease (CKD) in children and adults with spina bifida is considerable, rising, and entirely preventable. PREVENTION OF SPINA BIFIDA: The best prevention of CKD in spina bifida is prevention of spina bifida itself through strategies that include folate supplementation, ideally before pregnancy. Dysfunctional bladder outlet causes febrile Urinary Tract Infections (UTI), even with clean intermittent catheterization (CIC), and subsequent renal scarring. The development of secondary vesicoureteric reflux (VUR) increases the risk of renal scarring and CKD. Creatinine-based methods are insensitive because of low muscle mass and underdeveloped musculature in the legs. Only Cystatin C-based eGFR can reliably assess global renal function in these patients. However, unilateral renal damage requires nuclear medicine scans, such as (99m)Tc DMSA. (VIDEO)URODYNAMICS STUDIES (UDS): Early treatment is recommended based on UDS with anticholinergics, CIC, and antibiotic prophylaxis when indicated. Overnight catheter drainage, Botox, and eventually augmentation cystoplasty are required for poorly compliant bladders. A continent child or one rendered continent following surgery is at a higher risk of renal damage. A multidisciplinary approach is required to reduce the burden of CKD in patients with spina bifida. The right tools have to be utilized to monitor these patients, particularly if recurrent UTIs occur. Cystatin C eGFR is preferred for monitoring renal damage in these patients, and (99m)Tc DMSA scans have to be used to detect unilateral renal scarring.

The Role of Serum and Urine Interleukin-8 on Acute Pyelonephritis and Subsequent Renal Scarring in Children

Interleukin (IL)-8 acts as a potent neutrophils chemoattractant responsible for the migration of neutrophils into the infected renal tissue to protect against invading pathogens. The aim of this study was to assess the role of IL-8 on acute-phase pyelonephritis and later renal scarring in children. A total of 124 children with a first-time febrile urinary tract infection (UTI) were studied. The diagnosis of acute pyelonephritis was confirmed by Tc-dimercaptosuccinic acid (DMSA) renal scan. Serum and urine samples were obtained from 124 children with UTI and 20 healthy children for IL-8 measurement. The 124 children were divided into acute pyelonephritis (n = 70) and lower UTI (n = 54) groups according to the results of DMSA scans. The initial serum and urine IL-8 values of children with acute pyelonephritis were significantly higher when compared with lower UTI and healthy controls (all P < 0.001). Renal scarring was seen in 26 (38.8%) of these 67 children with acute pyelonephritis at follow-up DMSA scans. Both the initial serum and urine IL-8 concentrations were significantly higher in children with renal scarring than in those without (both P < 0.001). The mean age of children with renal scarring was also significantly lower than those without scarring (P = 0.004). Multivariate analysis showed that the highest initial IL-8 values, age <20 months and reflux grades > or =III all were independent predictors of renal scarring. Those children younger than 2 years of age with the highest IL-8 concentrations during the acute phase of pyelonephritis as well as children with reflux grades of III or greater are at a high-risk for developing renal scarring in the future.

Age-Related Renal Parenchymal Lesions in Children With First Febrile Urinary Tract Infections

The aim of this study was to define the association between age and the occurrence of acute pyelonephritis and renal scars. Between 1999 and 2002, all children 0 to 14 years of age consecutively seen with a first febrile urinary tract infection were enrolled in the study. (99m)Tc-Dimercaptosuccinic acid renal scintigraphy was performed within 5 days after admission for the detection of renal parenchymal involvement. The presence of vesicoureteral reflux was assessed by using cystography performed 1 month after the infection. If the acute scan results were abnormal, then follow-up (99m)Tc-dimercaptosuccinic acid scanning was performed after 6 months, to assess the frequency of scars. A total of 316 children were enrolled in the study (190 children <1 year, 99 children 1-4 years, and 27 children 5-14 years of age). (99m)Tc-Dimercaptosuccinic acid scintigraphy revealed that 59% of the children had renal involvement in the acute phase of infection. The frequency of kidney involvement in infants <1 year of age (49%) was significantly lower than that in children 1 to 4 years of age (73%) and >5 years of age (81%). Of the 187 children with positive acute (99m)Tc-dimercaptosuccinic acid scan results, 123 underwent repeat scintigraphy after 6 months. Renal scars were found for 28% of children <1 year, 37% of children 1 to 4 years, and 53% of children 5 to 14 years of age. No significant differences in the frequency of scars and the presence or absence of vesicoureteral reflux were noted. Our findings confirm that acute pyelonephritis and subsequent renal scarring occur only in some children with first febrile urinary tract infections. Children <1 year of age with febrile urinary tract infections have a lower risk of parenchymal localization of infection and renal scarring.

Procalcitonin as a predictor of renal scarring in infants and young children

The aim of this study was to evaluate the usefulness of procalcitonin (PCT) as a marker of renal scars in infants and young children with a first episode of acute pyelonephritis. Children aged 7 days to 36 months admitted for first febrile urinary tract infection (UTI) to a pediatric emergency department were prospectively enrolled. The PCT concentration was determined at admission. Acute (99m)Tc-dimercaptosuccinic acid (DMSA) scintigraphy was performed within 7 days of admission and repeated 12 months later when abnormal findings were obtained on the first scan. Of the 72 children enrolled in the study, 52 showed signs of acute pyelonephritis (APN) on the first DMSA scan. A follow-up scintigraphy at the 12-month follow-up performed on 41 patients revealed that 14 (34%) patients had developed renal scars; these patients also presented significantly higher PCT values than those without permanent renal lesions [2.3 (interquartile range 1-11.6) vs. 0.5 (0.2-1.4) ng/mL; p = 0.007]. A comparison of the PCT concentration in patients with febrile UTI without renal involvement, with APN without scar development and with APN with subsequent renal scarring revealed a significant increasing trend (p = 0.006, Kruskal-Wallis test). The area under the ROC curve for scar prediction was 0.74 (95% confidence interval 0.61-0.85), with an optimum statistical cut-off value of 1 ng/mL (sensitivity 78.6%; specificity 63.8%). Based on these results, we suggest that serum PCT concentration at admission is a useful predictive tool of renal scarring in infants and young children with acute pyelonephritis.

Treatment of Pyelonephritis and Risk of Renal Scarring

To the Editor. — In a secondary analysis of data from 2 randomized trials, Hewitt et al1 reached the conclusion that early treatment of acute pyelonephritis in infants and young children has no significant effect on the incidence of subsequent renal scarring. This conclusion was based, in part, on data from a clinical trial2 that enrolled children who had a first episode of febrile urinary tract infection (UTI) and met entry criteria for a “clinical diagnosis of acute pyelonephritis.” Importantly, one …

Relationship between serum and urine interleukin-6 elevations and renal scarring in children with acute pyelonephritis

Acute pyelonephritis is a common infectious disease in children and can result in permanent renal damage. Interleukin-6 (IL-6) is an important mediator of inflammation in response to bacterial infection. This study investigated the potential relationship between acute-phase IL-6 and subsequent renal scarring in children with a first time febrile acute pyelonephritis. In total, 79 children (age range 1-120 months) with a first time febrile urinary tract infection (UTI) were included. The diagnosis of acute pyelonephritis was confirmed by (99m)Tc-dimercaptosuccinic acid (DMSA) renal scan. Serum and urine samples were collected for IL-6 measurement by enzyme-linked immunosorbent assay before antibiotic treatment for the infection. The 79 children were divided into acute pyelonephritis (n=45) and lower UTI (n=34) groups according to the findings of DMSA scans. The initial serum and urine IL-6 levels of children with acute pyelonephritis were significantly higher compared with lower UTI (p < 0.001). Renal scarring was detected at the follow-up DMSA scans in 15 (34.1%) of the 44 children with acute pyelonephritis. Both serum and urine IL-6 levels during the acute phase of pyelonephritis were significantly higher in children with renal scarring than in those without (p=0.005 and p = 0.002). The median age of children with renal scarring was significantly lower than those without (p=0.034). Multiple regression analysis showed that higher initial serum and urine IL-6 levels and a younger age were associated with renal scarring. These results demonstrate that in younger children with a first time febrile acute pyelonephritis, elevations of the acute-phase serum and urine IL-6 levels were correlated with an increased risk of subsequent renal scarring.

Early Antibiotic Treatment of Pyelonephritis in Children Is Still Mandatory

To the Editor. We read with interest the study by Hewitt et al1 on the effect of early treatment on the development of renal scarring in children with acute pyelonephritis. They found that early treatment of acute pyelonephritis had no significant effect on the incidence of subsequent renal scarring and, therefore, found it …

The Role of Vesicoureteral Reflux in Acute Renal Cortical Scintigraphic Lesion and Ultimate Scar Formation

We assessed whether differences exist in the rates of acute photon defect and scar formation using dimercapto-succinic acid scintigraphy according to the presence and grade of vesicoureteral reflux. A total of 389 patients with a first febrile urinary tract infection were enrolled. For all patients ultrasonography, dimercapto-succinic acid scintigraphy and voiding cystourethrography were performed. Dimercapto-succinic acid scintigraphy was performed within 5 days of and 6 months after diagnosis of urinary tract infection. Voiding cystourethrography was performed after the acute phase of urinary tract infection. The rates of acute photon defect and scar formation on dimercapto-succinic acid scintigraphy according to the presence and grade of vesicoureteral reflux were assessed. A total of 125 females and 264 males were included in the study. Of the patients 93 had refluxing urinary tract infection and 296 had nonrefluxing infection. The rate of acute photon defect (74.2% vs 32.1%, p = 0.0001) and the rate of ultimate scar change on followup dimercapto-succinic acid scintigraphy were significantly higher in patients with refluxing urinary tract infection (50% vs 18.3%, p = 0.0001). Positive linear association was noted between reflux grade and acute photon defect by linear association test (p = 0.002). No association was found between reflux grade and scar formation (p = 0.262). Although vesicoureteral reflux is not a prerequisite for development of acute photon defect and subsequent renal scarring, reflux itself might be an aggravating factor for acute photon defect and scar formation. There seems to be a correlation between reflux grade and frequency of acute photon defect on dimercapto-succinic acid scintigraphy but scar change occurs independently of reflux grade.

Early Treatment of Acute Pyelonephritis in Children Fails to Reduce Renal Scarring: Data From the Italian Renal Infection Study Trials

The American Academy of Pediatrics recommendation for febrile infants and young children suspected of having a urinary tract infection is early antibiotic treatment, given parenterally if necessary. In support of this recommendation, data suggesting that delay in treatment of acute pyelonephritis increases the risk of kidney damage are cited. Because the risk was not well defined, we investigated renal scarring associated with delayed versus early treatment of acute pyelonephritis in children. The research findings are derived from 2 multicenter, prospective, randomized, controlled studies, Italian Renal Infection Study 1 and 2, whose primary outcomes dealt with initial antibiotic treatment and subsequent prophylaxis, respectively. From the 2 studies, we selected the 287 children with confirmed pyelonephritis on acute technetium-99m-dimercaptosuccinic acid scans who underwent repeat scanning to detect scarring 12 months later. The children were 1 month to <7 years of age when they presented with their first recognized episode of acute pyelonephritis in northeast Italy. Progressive delay in antibiotic treatment of acute pyelonephritis from <1 to >/=5 days after the onset of fever was not associated with any significant increase in the risk of scarring on technetium-99m-dimercaptosuccinic acid scans obtained 1 year later. The risk of scarring remained relatively constant at 30.7 +/- 7%. Clinical and laboratory indices of inflammation were comparable in all groups, as was the incidence of vesicoureteric reflux. Early treatment of acute pyelonephritis in infants and young children had no significant effect on the incidence of subsequent renal scarring. Furthermore, there was no significant difference in the rate of scarring after acute pyelonephritis when infants and young children were compared with older children.

Dual effects of Escherichia coliα-hemolysin on rat renal proximal tubule cells

alpha-Hemolysin (HlyA) producing Escherichia coli is a common cause of pyelonephritis and subsequent renal scarring. Recent studies have suggested that toxin secreted from HlyA E. coli may not only have a lytic effect, but also may activate a calcium signaling pathway in renal tubule cells. A dose dependent study was performed on the interaction between HlyA E. coli secretions and rat renal proximal tubule (PT) cells with regards to calcium signaling and cell morphology. The site of interaction between HlyA secretion and PT cells was examined by using an antagonist to a common binding motif in bacterial proteins. Supernatant from an overnight culture of HlyA was freshly prepared for each experiment. Renal PT cells from infant rats were cultured for three days and exposed for 30 minutes to four hours to supernatant or purified HlyA. Effects on cell morphology were studied semiquantitatively with light microscopy. Intracellular calcium was measured ratiometrically in the presence or absence of drugs. Renal PT cells incubated with low doses of HlyA supernatant responded within five minutes with calcium oscillations. Morphology appeared unchanged after four hours of incubation. In contrast, high doses of HlyA caused a sustained increase in intracellular calcium and majority of cells were lysed within four hours. Calcium oscillations caused by lower doses of HlyA supernatant were highly regular and slow in the 10 to 12 minute range. Oscillations were abolished by 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX), indicating that HlyA is interacting with a QPB/LAOBP-motif. HlyA secreted from uropathogenic E. coli exerts a dual action on renal PT cells. Sublytical concentrations induce a response that may serve as a host defense, while high concentrations cause irreversible cell damage. The data emphasize the importance of high diuresis in urinary tract infection.