Current imaging of childhood urinary infections: prospective survey.

OBJECTIVES--To assess whether ultrasonography alone is adequate for routine screening of childhood urinary infection, whether clinical features determine the need for further investigations, and which investigations are most appropriate. DESIGN--Prospective survey of children with proved urinary infection and a preinvestigation record of clinical features. Ultrasonography and intravenous urography were routine, with choice of further studies determined by ultrasonographic findings. SETTING--A children''s hospital and two district general hospitals in Mersey region. MAIN OUTCOME MEASURES--Sensitivity and specificity of ultrasonography both generally and in relation to clinical features. Accuracy of intravenous urography compared with radioisotope examinations. RESULTS--Specificity of ultrasonography was good (99% (95% confidence interval 96% to 100%)) but sensitivity modest (43% (32% to 55%)), principally with respect to detecting vesicoureteric reflux and renal scarring. Among older children (aged 2-10 years) with positive ultrasound results and fever or vomiting the sensitivity in detecting reflux (with and without renal scarring) was 78% (62% to 89%) and the specificity 69% (60% to 78%); in detecting renal scarring (with and without reflux) the sensitivity was 100% (80% to 100%) and specificity 65% (56% to 74%). Renal scarring and obstructive uropathies were better assessed by radioisotope examinations than by intravenous urography. CONCLUSIONS--Ultrasonography alone is inadequate for routine screening of childhood urinary infection. Though further investigations remain advisable in infants, in older children they can be restricted to a minority who have positive ultrasound examinations or have had fever or vomiting. Radioisotope examinations largely eliminate the need for intravenous urography.     

Retrospective study of children with renal scarring associated with reflux and urinary infection.

OBJECTIVE--To review the histories of children with bilateral renal scarring and severe vesicoureteric reflux to determine whether an improvement in early management might reduce the risk of scarring. DESIGN--Retrospective study of medical records and discussion with parents. SETTING--Outpatient departments of two teaching hospitals. PATIENTS--52 children aged 1-12 years participating in a randomised comparison of medical and surgical management. All had a history of symptomatic urinary tract infection. Two thirds presented with fever and two with hypertension or renal failure. In only one out of 32 children examined by antenatal ultrasonography was an abnormality suspected. RESULTS--There was delay in diagnosis or appropriate imaging or effective treatment of urinary infection in 50 of the 52 children. In 41 there was delay in diagnosis; there was delay in treating a confirmed infection in 45; no antibacterial prophylaxis was prescribed before imaging in 28; and investigation of the urinary tract was delayed in 33. The severity of scarring was significantly related to delay in diagnosis (chi 2 for trend 7.43, P = 0.01). Four children of mothers known to have reflux nephropathy were not investigated until they developed urinary tract infection. CONCLUSIONS--Efforts to reduce the incidence and severity of renal scarring should be directed towards rapid diagnosis and effective early management of urinary tract infection in infancy and childhood. Siblings and offspring of known patients with severe reflux nephropathy should be investigated for reflux.     

Urinary tract infections in children. An update.

Urinary tract infection is a common and frequently recurring condition in children. The susceptibility of the host, the presence of urinary tract abnormalities, and the virulence of the urinary pathogens are of primary importance in the development of the infection. Renal parenchymal scarring, hypertension, and renal insufficiency are well-established complications of the infection in children. To reduce the risk of renal damage, diagnosis and treatment must be prompt. The diagnosis demands radiologic evaluation of the urinary tract in all boys, all children younger than 5 years, all patients with voiding dysfunction, and school-aged girls with recurrent infection to identify those patients with vesicoureteral reflux, obstruction, or other urinary tract abnormalities. Both voiding cystourethrography and renal ultrasonography are the initial examinations to use to determine the next appropriate study. Children with vesicoureteral reflux or with recurrent urinary tract infections should receive prophylactic antibiotic therapy and should be observed closely to prevent renal scarring.     

Part II – Roentgenologic Aspects

Roentgen findings in 107 girls under the age of ten years who had proven recurrent urinary tract infections were analyzed. From the excretory urograms done on these children, renal and pelvocalyceal outlines were accurately traced. Subsequently, renal length and parenchymal thickness at multiple points were measured. The presence or absence and grade of reflux were determined by voiding cystourethrography. Finally, the clinical history was correlated with the roentgen findings.With three exceptions, scarring and clubbing in the presence of infection occurred only in refluxing renal units. Kidneys exposed to a higher grade of reflux more frequently showed scarring and clubbing (p<0.001). Seventeen out of 40 renal units either developed or had increase in clubbing and scarring while the patients were being followed. After surgical correction of reflux, 16 of 24 previously clubbed and scarred kidneys showed progression of the lesions, usually within 24 months after operation. All children whose kidneys showed progression after surgical operation had experienced an episode of acute urinary infection with chills and fever before operation.No significant difference existed in the age at clinical onset of infection in patients with ureteral reflux with or without roentgen evidence of clubbing and scarring. This study documents the close relationship between clubbing and scarring and reflux in the presence of urinary infection in infants and children.     

Update on vesicoureteral reflux: pathogenesis, nephropathy, and management

Clinical reflux was first visualized over 100 years ago. In the 1950s and early 1960s, the assumption was that surgery to relieve bladder neck obstruction would have a positive effect on bladder function and reflux. By the early 1970s it was understood that the underlying structural problems leading to primary reflux were congenitally abnormal distal ureters and orifices. Researchers in the 1960s and 1970s demonstrated the connection between reflux and renal scarring. More recently, reflux nephropathy in the absence of urinary tract infections has been observed, leading researchers to investigate an association between bladder dysfunction and reflux with resulting nephropathy. The cornerstone of management of the child with vesicoureteral reflux is antibiotic prophylaxis; treatment regimens for various grades of reflux are reviewed. Indications for surgical treatment of reflux are also discussed. Controversies regarding vesicoureteral reflux, including duration of prophylactic treatment, remain to be resolved.     

Development of new renal scars: a collaborative study.

In a study of the factors surrounding the development of renal scars clinical data and serial radiographs were analysed in 74 infants and children (66 girls and eight boys) without duplex kidney or obstruction. The development of new scars was seen radiologically in 87 kidneys (74 previously normal and 13 previously scarred). New scarring was extensive in 16 kidneys. Thirty four children were aged 5 or over when scarring occurred. Urinary infection occurred in all the children. Diagnosis and effective treatment were delayed in 45 of them; 58 suffered further urinary infections between the baseline intravenous urogram and the first showing new scarring. Vesicoureteric reflux was seen in 67 of the children. Investigation and treatment varied widely, and few children received long term prophylaxis. Social problems interfered with the management of 22 children. Early diagnosis, prompt effective treatment, investigation, and long term supervision of children with urinary infection are essential if renal scarring is to be reduced; those over the age of 5 are still vulnerable.     

Cystographie isotopique indirecte couplée à la scintigraphie rénale corticale et détection des reflux vésicorénaux chez les nourrissons et les enfants atteints de pyélonéphrite

Vesico-uretero-renal reflux (VRR) and urinary tract infection are closely linked. Without any treatment, reflux nephropathy, hypertension and renal dysfunction are very often encountered. That is why a precocious and reliable diagnosis of RVR should be made. Our retrospective study included 33 infants and children suffering from acute pyelonephritis (APN). They were explored by both 99mTc-MAG3 indirect isotopic cystography (IIC), 99mTc-DMSA cortical renal scintigraphy performed on the same day, and radiological retrograde cystography (RRC). A VRR was expected on the same side than the pyelonephritic kidney. Results from IIC versus RRC and versus renal cortical acute pyelonephritis lesions, which were proved by the “gold standard” DMSA scan, were obtained. IIC detected a same-sided VRR in 52% and CRR in 33% of our patients. Some of them had bilateral lesions. IIC detected an homolateral VRR in 59% instead of 38% with RRC (P < 0.05). IIC is a physiological noninvasive examination with a convenient sensitivity and dosimetry to search a VRR. Moreover, it gives in the same time interesting functional information on the kidneys and the urinary tract. Each of these characteristics can be favorably compared with RRC.     

Prospective trial of operative versus non-operative treatment of severe vesicoureteric reflux in children: five years' observation. Birmingham Reflux Study Group.

Children with severe vesicoureteric reflux were allocated randomly to either operative or non-operative treatment and followed up. Altogether 161 children were observed for two years, of whom 104 were followed up for five years. Reflux was abolished in 98% of ureters reimplanted, but more than half of the patients treated non-operatively continued to show severe reflux at five years. Two patients progressed to end stage renal failure, and a further four with extensive bilateral renal scarring became hypertensive. There were no significant differences between treatment groups in the incidence of breakthrough urinary infection, renal excretory function and concentrating ability, renal growth, progression of existing renal scars, or new scar formation. Progressive scarring occurred at all ages but was significantly more common during the first two years'' observation. Furthermore, new scars developed exclusively during the first two years'' observation, affecting 10 children aged 2-7 at allocation. Neither treatment can claim superiority or fully protect the kidneys from further damage, and efforts must continue to be directed towards identifying those at risk before scarring develops.     

Ultrasonography compared with intravenous urography in investigation of urinary tract infection in adults.

OBJECTIVE--To compare ultrasonography with intravenous urography for investigating adults with proved urinary tract infection. DESIGN--Prospective study of patients presenting consecutively for radiological investigation of urinary tract infection between October 1988 and December 1989. Both investigations were performed concurrently and performed independently on routine lists by different duty radiologists, each of whom knew the details on the request form but not the findings of the other investigation. SETTING--Radiology department of a teaching hospital. PATIENTS--158 Consecutive adults (89 women, 69 men; mean age 49.7 (range 18-83)) referred from general practitioners and hospital outpatient clinics with a history of proved urinary tract infection. INTERVENTIONS--Urography and ultrasonography performed concurrently. When both examinations gave normal findings no clinical or radiological follow up was sought. All abnormal findings detected with either investigation were confirmed by subsequent imaging studies or by operative procedures. MAIN OUTCOME MEASURE--Accuracy of detection of abnormalities of urinary system by ultrasonography compared with urography. RESULTS--113 Patients (72%) had normal urographic and ultrasonic findings. Overall, ultrasonography concurred with the findings of urography in 149 (94%) patients, and when a single abdominal radiograph was included in the procedure, in 152 (96%). Ultrasonography missed only one important diagnosis, that of mild papillary necrosis in normal sized kidneys in a diabetic patient. It detected one early bladder tumour not visible on urography and was able to clarify the nature of renal masses (simple cysts) evident on three urograms. CONCLUSION--Ultrasonography provides a safe and accurate method of imaging the urinary tract in adults with infection. Combined with a plain abdominal radiograph, it should replace urography as the initial imaging investigation in these patients. Major savings would result from adopting this policy, and the risks to patients from ionising radiation and intravenous contrast media would be appreciably reduced.     

Ultrasonography and abdominal radiography versus intravenous urography in investigation of urinary tract infection in men: prospective incident cohort study

ObjectivesTo compare ultrasonography and abdominal radiography with intravenous urography in the investigation of urinary tract infection in men.DesignProspective study in two hospital departments. Radiological procedures and urological assessments performed on different days by different cliniciansSettingDistrict general hospital.ParticipantsConsecutive series of men (n=114) referred to the department of urology for investigation of proved urinary tract infection.InterventionsUltrasonography and intravenous urography of renal tract and assessment of urinary flow rate. Clinical assessment, cystoscopy, urodynamic studies, and transrectal ultrasonography with biopsy.ResultsImportant abnormalities were seen in 53 of 100 fully evaluated patients, the most common being a poorly emptying bladder (34). The combination of plain radiographs of kidneys, ureter, and bladder and ultrasonography detected more abnormalities than intravenous urography alone. No important abnormality was missed by this combination (sensitivity 100% and specificity 93%).ConclusionsUltrasonography with abdominal radiography is as accurate as intravenous urography in detecting important urological abnormalities in men presenting with urinary tract infection. This combination is safer than intravenous urography and should be the initial investigation for such patients. Additional determination of urinary flow rate is useful for the assessment of an incompletely emptying bladder.

What is already known on this topic

Ultrasonography alone is the primary investigation of choice for urinary tract infection in children and womenUltrasonography has limited sensitivity for renal stones and poor sensitivity for ureteric stonesUrinary infection is less common in men than women and the risk factors are different

What this study adds

Ultrasonography is as effective as intravenous urography in men with urinary tract infection only when it is combined with plain radiographyIn men aged over 50 an incompletely emptying bladder is the most common abnormalityIn such patients determination of urinary flow rate is particularly helpful     

Chronic renal failure in children.

Seventy-seven children with chronic renal failure were examined at one hospital in the province of Quebec between 1970 and 1975; this represents an incidence of 2.5 per million population per year. The entities responsible for chronic renal failure were urinary tract malformation (in 36%), chronic glomerulonephritis (in 22%), congenital renal parenchymal malformation (in 21%) and hereditary nephropathy (in 13%). The evolution of chronic renal failure in children with either vesicoureteral reflux or a posterior urethral valve seemed to be related more to the initial severity of the disease than to the age at the time of diagnosis. Hence any screening program designed to detect kidney disease in schoolchildren would not prevent chronic renal failure, since at that age renal parenchymal damage seems to be irreversible. The manner in which chronic glomerulonephritis evolved depended on whether the nephrotic syndrome was present and on the type of histologic lesion. Children with congenital renal hypoplasia or dysplasia often presented with seizures due to hypertensive encephalopathy without obvious symptoms or signs of pre-existing renal disease. Among patients with familial nephropathy many of those with cystinosis underwent successful renal transplantation early in life.     

Tumor markers (CEA, TPA and CA 19-9) in urine of bladder cancer patients

This study was carried out to evaluate the usefulness of determining urinary levels of carcinoembryogenic antigen (CEA), tissue-polypeptide antigen (TPA), and gastro-intestinal cancer antigen (Ca19-9) in addition to the usual diagnostic procedures for bladder cancer. Sixty-seven patients with transitional bladder cancer, 40 healthy controls and 20 patients with inflammatory diseases of the urinary tract were considered. All urine samples were obtained from patients with intact renal function and no urinary tract infection. TPA and Ca19-9 urinary levels in patients with G3 bladder tumors were significantly higher than in those with lower graded neoplasms. The sensitivity, specificity, and predictive value of a positive (PV+) or negative (PV-) test and the diagnostic accuracy were also evaluated. Ca19-9 was the best urinary marker for bladder cancer (sensitivity 71.6%, specificity 91.6%, PV+ 90.5%, PV- 74.3%, diagnostic accuracy 81%).     

Pregnancies in women with and without renal scarring after urinary infections in childhood.

OBJECTIVE--To compare the outcome of pregnancy in women with and without renal scarring after childhood urinary infections with that in unmatched controls. DESIGN--Retrospective study of pregnancies in women prospectively followed up from their first recognised urinary infection. SETTING--Tertiary referral centre in Gothenburg. SUBJECTS--111 Women attending an outpatient clinic for women with urinary infection during 1975-83, of whom 41 (65 pregnancies) were studied (19 women with renal scarring (32), 22 without scarring (33)), and 65 controls (65) randomly selected and matched for parity, age, smoking habits, and date of delivery. MAIN OUTCOME MEASURES--Urinary infections and complications in pregnancy. RESULTS--The incidence of bacteriuria during first pregnancies was significantly greater in women with (9, 47%) and without (6, 27%) renal scarring after childhood urinary infection than in controls (1, 2%) (p less than 0.001, 0.01 respectively). Symptomatic infections were seen only among women with a history of urinary infection: four women with renal scarring (three of whom had vesicoureteric reflux) developed pyelonephritis and three cystitis, and one woman without scarring developed pyelonephritis. Mean blood pressure was higher among women with severe renal scarring than controls (4/11 v 3/44; p less than 0.05) before and during pregnancy. There was no significant difference in the incidence of pre-eclampsia, operative delivery, prematurity, or birth weight. CONCLUSIONS--Women with a history of previous urinary infections had a high incidence of bacteriuria during pregnancy, and those with renal scarring and persistent reflux were prone to develop acute pyelonephritis. The risk of serious complications in pregnancy, however, was not increased in women with severe renal scarring, possibly owing to their continuous clinical supervision.     

Genetics of Vesicoureteral Reflux

Vesicoureteral reflux (VUR) is the retrograde passage of urine from the bladder to the upper urinary tract. It is the most common congenital urological anomaly affecting 1-2% of children and 30-40% of patients with urinary tract infections. VUR is a major risk factor for pyelonephritic scarring and chronic renal failure in children. It is the result of a shortened intravesical ureter with an enlarged or malpositioned ureteric orifice. An ectopic embryonal ureteric budding development is implicated in the pathogenesis of VUR, which is a complex genetic developmental disorder. Many genes are involved in the ureteric budding formation and subsequently in the urinary tract and kidney development. Previous studies demonstrate an heterogeneous genetic pattern of VUR. In fact no single major locus or gene for primary VUR has been identified. It is likely that different forms of VUR with different genetic determinantes are present. Moreover genetic studies of syndromes with associated VUR have revealed several possible candidate genes involved in the pathogenesis of VUR and related urinary tract malformations. Mutations in genes essential for urinary tract morphogenesis are linked to numerous congenital syndromes, and in most of those VUR is a feature. The Authors provide an overview of the developmental processes leading to the VUR. The different genes and signaling pathways controlling the embryonal urinary tract development are analyzed. A better understanding of VUR genetic bases could improve the management of this condition in children.     

Part III – Treatment of Ureterovesical Reflux

Of 134 girls with demonstrable ureterovesical reflux, 61 (105 ureters) had the reflux surgically corrected with an overall surgical cure rate of 97 percent. In the remaining 73 children (112 ureters), the reflux was treated conservatively with medical management alone. During the follow-up period no significant differences were demonstrated in the overall incidence of urinary tract infection; two years following corrective operation or medical treatment more than 50 percent of both medically and surgically treated children were still experiencing infections. A pronounced decrease, however, occurred in the incidence of clinical pyelonephritis among the surgically treated group. Following correction of reflux, the incidence of pyelonephritis was similar in both medically and surgically treated cases and was approximately the same as that found in a comparable group of children without reflux.In approximately two-thirds of refluxing renal units in which there was evidence of clubbing and scarring before medical or surgical therapy, deterioration progressed during the follow-up period. In most of these cases infection control was felt to be inadequate with episodes of clinical pyelonephritis occurring during the period of medical management, or, in the surgically treated group, occurring just before corrective operation and the scar appearing within two years after operation.The majority of renal units in which calyceal clubbing and parenchymal scarring was present had the most severe grades of reflux.     

Ultrasonography compared with intravenous urography in the investigation of adults with haematuria.

OBJECTIVE--To compare ultrasonography with intravenous urography in the investigation of adults with haematuria. DESIGN--Prospective study entailing the examination of all patients with both investigations concurrently. The investigations were performed independently on routine lists by different duty radiologists. Each was aware of the details of the request form but not of the findings of the other investigation. SETTING--Radiology department of a teaching hospital. PATIENTS--155 Consecutive adult patients (aged 18-93) referred from general practitioners and hospital outpatient clinics with a history of haematuria. FOLLOW UP--When results of both examinations proved normal no clinical or radiological follow up was sought. All abnormal findings of either investigation were correlated with results of subsequent imaging studies or operative findings. RESULTS--81 Patients (52%) had normal findings on urography and ultrasonography. Overall, the findings of ultrasonography concurred with those of urography in 144 cases (93%). Among the discrepant findings of the two investigations ultrasonography missed two ureteric calculi; one was in a non-dilated ureter, and in the other case ultrasonography detected the secondary ureteric dilatation. Ultrasound examination alone detected four bladder tumours not visible on urography with sizes ranging from 5 to 21 mm, representing one fifth of the 20 cystoscopically proved bladder tumours detected in the series. Ultrasonography detected all the 22 neoplastic lesions discovered in the study (20 bladder, two renal). Ultrasonography clarified the nature of renal masses evident in three urograms (simple cysts). CONCLUSIONS--Ultrasonography is a safe and accurate method of investigating the urinary tract in adults with haematuria. When combined with a single plain abdominal radiograph it proved to be superior to urography as the primary imaging study in this series. Ultrasonography should certainly be preferred to urography if cystoscopy is not planned. No urothelial tumours of the upper urinary tract were found in the series, reflecting their rarity. For those patients in whom ultrasonography and plain radiography have shown no abnormality and in whom cystoscopic appearances are normal urography would be advisable to exclude urothelial tumours of the upper urinary tract.     

The role of Tamm-Horsfall protein in the pathogenesis of reflux nephropathy and chronic pyelonephritis

Recurrent bacterial infection of the kidney was previously thought to be responsible for the renal scarring typical of chronic pyelonephritis until recent studies suggested that recurrent bacteriuria rarely produces chronic pyelonephritis in the absence of obstructive uropathy. In contrast, the association between vesicoureteral reflux (VUR) and chronic pyelonephritis has been observed frequently in the absence of urinary infection. Although the mechanism by which VUR injures the kidney has not been defined, recent observations have suggested that some component of urine might serve as an antigenic determinant involved in the immunopathogenesis of renal scarring in VUR. Therefore, the present studies investigated the immunopathogenic role of Tamm-Horsfall protein (THP) in (1) a rabbit model of tubulointerstitial nephritis; (2) a swine model of reflux nephropathy; and (3) patients with recurrent nephrolithiasis. The antigenic similarities between THP and uropathic bacteria were also studied. Our observations indicate that autoimmune responses to THP may occur after exposure to THP by intravenous challenge in rabbits, by urinary reflux in pigs, and in recurrent nephrolithiasis in man. Also, extracts of uropathic coliforms competitively inhibit the binding of human THP to its antibody. These studies suggest that autoimmune responses to THP may be the pathogenetic mechanism by which these factors, including bacteriuria, contribute to "chronic pyelonephritis."     

Congenital anomalies of the kidney and urinary tract: An embryogenetic review

Congenital anomalies of the kidney and urinary tract (CAKUT) represent a broad range of disorders that result from abnormalities of the urinary collecting system, abnormal embryonic migration of the kidneys, or abnormal renal parenchyma development. These disorders are commonly found in humans, accounting for 20–30% of all genetic malformations diagnosed during the prenatal period. It has been estimated that CAKUT are responsible for 30–50% of all children with chronic renal disease worldwide and that some anomalies can predispose to adult‐onset diseases, such as hypertension. Currently, there is much speculation regarding the pathogenesis of CAKUT. Common genetic background with variable penetrance plays a role in the development of the wide spectrum of CAKUT phenotypes. This review aims to summarize the possible mechanisms by which genes responsible for kidney and urinary tract morphogenesis might be implicated in the pathogenesis of CAKUT. Birth Defects Research (Part C) 102:374–381, 2014. © 2014 Wiley Periodicals, Inc.     

肺脏超声对新生儿呼吸窘迫综合征的诊断价值及肺超声评分的评估价值分析

目的:探讨肺脏超声对新生儿呼吸窘迫综合征(NRDS)的诊断价值,并分析肺超声评分的临床应用价值。方法:本研究选择2017年5月至2018年5月于我院确诊的NRDS患儿45例作为观察组,选择同期于我院就诊的非肺病患儿45例作为对照组,所有患儿均行肺脏超声检查。分析NRDS患儿肺脏超声特征性征象,比较肺脏超声对两组患儿各种征象的检出率,分析肺脏超声对NRDS的诊断价值,比较两组肺超声评分。结果:NRDS患儿全部存在肺实质征象,超声下肺组织回声呈肝样伴支气管充气征,轻度的NRDS患儿于肺脏超声下表现为局灶性的肺实质,且支气管充气征不明显;重度的NRDS患儿于肺脏超声下表现为肺实质范围的进一步扩大,且支气管充气征随病情的加重而愈发明显。观察组肺实质、胸膜线异常、A线消失、弥漫性肺水肿、支气管充气征等征象的检出率显著高于对照组(P0.05),两组B线存在征象的检出率比较无统计学差异(P0.05)。肺实质、胸膜线异常和A线消失三种特征征象同时存在时对NRDS诊断的灵敏度和特异性均为100.00%,肺实质、胸膜线异常和支气管充气征三种特征征象同时存在时对NRDS诊断的灵敏度为80.00%,特异性为100.00%。观察组双肺、左肺、右肺、双侧肺、双肺底肺超声评分均高于对照组(P0.05)。结论:肺脏超声对NRDS的诊断价值较高,且肺超声评分可以评估NRDS患儿的病情严重程度,有助于指导患儿的治疗。