Development of hypertension and uraemia after pyelonephritis in childhood: 27 year follow up.

OBJECTIVE--Determination of the long term incidence of uraemia, hypertension, and toxaemia in pregnancy associated with non-obstructive focal renal scarring after pyelonephritis in childhood 25-35 years earlier. DESIGN--27 Year follow up of patients with non-obstructive focal scarring identified from a retrospective review of intravenous urograms performed in childhood between 1951 and 1967. SETTING--Paediatric primary referral centre and urological clinic in tertiary referral centre. PATIENTS--30 Patients (mean age 33 (range 22-41] with non-obstructive focal renal scarring first detected between 1951 and 1967 and a history of febrile urinary tract infection. MAIN OUTCOME MEASURE--Hypertension and complications of renal damage. RESULTS--Three patients had developed end stage renal disease, seven had developed hypertension, two of 16 women had a history of toxaemia during pregnancy, and seven patients had undergone renal surgery during follow up. Of the 20 patients who had neither had renal surgery nor had end stage renal disease, all had a significantly lower glomerular filtration rate and renal plasma flow and higher diastolic blood pressure, mean arterial blood pressure, plasma renin activity, and serum beta 2 microglobulin concentration than 13 healthy age matched controls. Diastolic blood pressure and plasma renin activity were positively correlated (r = 0.50, p less than 0.05) and so were fractional sodium excretion and both systolic and diastolic blood pressures (r = 0.54, p less than 0.01, r = 0.51, p less than 0.01 respectively). The progress of renal damage was unrelated to the incidence of recurrent infections. CONCLUSIONS--Children with focal renal scarring due to pyelonephritis are at high risk of serious long term consequences. It is essential that they are given adequate attention and care during adolescence and pregnancy.     

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.     

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."     

Epidemiology of urinary tract diseases in general practice

During a one-year morbidity survey of urinary tract diseases in general practice 741 cases were diagnosed. Only about half of all the patients with symptoms of urinary tract infection had significant bacteriuria. In young women urinary tract infections and symptoms from the urinary tract without bacteriuria—in particular urethritis—were found to predominate. In middle-aged women, the urinary tract symptoms were ascribed increasingly to genital prolapse, while incidence of urolithiasis was the highest in any group, and urinary tract infections became less frequent. The prevalence of urinary tract infection showed another increase in elderly women, and recurrent/chronic pyelonephritis, which occurs with a steadily increasing prevalence throughout all age groups, became common.In younger male urological patients diseases with symptoms of urinary tract infection without bacteriuria were predominant, whereas prostatitis and urinary tract infections were less frequent. In middle-aged men, urolithiasis was especially frequent, while an increasing proportion of elderly men had prostatic hypertrophy, urinary tract infections, and recurrent/chronic pyelonephritis.     

Retrospective studies of urinary infections in the elderly

Retrospective analysis of the urinary infection course involved 55 elderly patients. The patients were divided into groups basing on the clinical diagnosis. These groups included patients with obstructive chronic pyelonephritis and the patients with lower urinary infections. It was found that reinfections occur in the elderly patients with both upper and lower urinary infections while recurrence is seen in case of the upper urinary infections. Bacteriuria is significantly more frequent in the obstructive chronic pyelonephritis than in other urinary infections. This form of bacteriuria is frequently accompanied by exacerbations than in bacteriuria of periodic origin. Arterial blood hypertension is frequent in the elderly with urinary infections but its incidence does not correlate with the localization of the infection. Decompensated renal failure in the course of the urinary infections in the elderly is nearly always combined with arterial blood hypertension.     

Urinary Concentrating Ability in Women with Asymptomatic Bacteriuria in Pregnancy

The incidence of impaired renal concentrating ability in pregnant women with asymptomatic significant bacteriuria is significantly less than previously reported when osmolality readings are performed on every urine specimen obtained during the 24 hours'' deprivation of fluids. The concentrating defect is more considerable as pregnancy progresses. The lower the maximum urinary osmolality the more difficult is the treatment of the patient, and the higher the incidence of acute pyelonephritis.     

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.     

Study of Childhood Urinary Tract Infection in General Practice

A study of bacteriuria was conducted among 426 of the 436 children under the age of 13 in a general practice in north-west London. Three girls and one boy were found to have asymptomatic bacteriuria, and a further girl with bacteriuria presented with abdominal pain and fever. The calculated incidence of urinary tract infection was 1·4% per annum. Most of the childhood urinary infections in this practice occurred before the age of 5 years, and the incidence of significant bacteriuria in this age group was 4·9% per annum. Five other children (four girls and one boy) in the practice were known to have had proved urinary tract infection. Of the total of eight children known to have had significant bacteriuria and investigated radiologically, three girls and two boys had radiological abnormalities in the urinary tract.Pyuria and proteinuria did not prove to be useful in the prediction of asymptomatic bacteriuria. Urinary tract infection with renal tract abnormality was found in this practice to be at least five times as common as diabetes in childhood.     

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.     

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.     

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.     

Secretor state and renal scarring in girls with recurrent pyelonephritis

Abstract The non-secretor phenotype was significantly associated with the occurrence of renal scarring among patients with recurrent pyelonephritis. Girls ( n = 77) with recurrent pyelonephritis were followed from the first known episode of infection for up to twelve years with repeated radiological investigations. They were divided into two categories: those with renal scars ( n = 35) and those who did not develop scars ( n = 42). There was a significant over-representation of non-secretors among the patients with scarring, (14/35, 40%) compared to the healthy controls (21.8%, P < 0.05). The frequency of non-secretors among the girls who did not develop scars in spite of repeated episodes of acute pyelonephritis was not significantly different from the healthy controls (9/42, 21%, n.s.). This study provides a basis for analysis of the influence of secretor state on host-parasite interaction in the urinary tract.     

Reliability of ultrasonography in identification of reflux nephropathy in children.

OBJECTIVE--To assess the ability of ultrasonography to identify reflux nephropathy in children after urinary tract infection. DESIGN--Ten experienced radiologists performed a total of 240 ultrasonographic examinations of kidneys in a one day study. The examiners were unaware of the results of previous radiological and clinical examinations and of the proportions of normal and abnormal kidneys. Urography was used as method of reference, supported by static renal scintigraphy (dimercaptosuccinic acid labelled with technetium-99m) in half of the cases. SETTING--Outpatient radiology department. SUBJECTS--25 children aged 2-16 years (20 kidneys with and 30 kidneys without renal scarring). MAIN OUTCOME MEASURES--Renal scarring. Overall size and length of kidneys. Sensitivity and specificity including receiver operator characteristics and variation between observers. RESULTS--With renal scarring as the diagnostic criterion and including cases classified as abnormal, probably abnormal, and uncertain the sensitivity of ultrasonography was 54% (specificity 80%). Addition of reduced renal size as a diagnostic criterion increased the sensitivity to 64% (specificity 79%). There were, however, wide variations between observers, with sensitivity ranging between 40% and 90% (specificity 94% to 65%). CONCLUSIONS--Because of its low sensitivity and specificity and poor agreement between observers, ultrasonography cannot be generally recommended for the detection of reflux nephropathy after urinary tract infection in children.     

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.     

Secretor state and renal scarring in girls with recurrent pyelonephritis

The non-secretor phenotype was significantly associated with the occurrence of renal scarring among patients with recurrent pyelonephritis. Girls (n = 77) with recurrent pyelonephritis were followed from the first known episode of infection for up to twelve years with repeated radiological investigations. They were divided into two categories: those with renal scars (n = 35) and those who did not develop scars (n = 42). There was a significant over-representation of non-secretors among the patients with scarring, (14/35, 40%) compared to the healthy controls (21.8%, P less than 0.05). The frequency of non-secretors among the girls who did not develop scars in spite of repeated episodes of acute pyelonephritis was not significantly different from the healthy controls (9/42, 21% n.s.). This study provides a basis for analysis of the influence of secretor state on host-parasite interaction in the urinary tract.     

Asymptomatic Urinary Tract Infection in Gynaecological Outpatients

In this study mid-stream specimens of urine were collected from all new patients attending a gynaecological outpatient department and tested for significant bacteriuria. Those having an asymptomatic infection were folloWed up, treated, and investigated adiologically.Of 1,506 women screened for bacteriuria 82 (5·4%) were found to have a persistent infection. The predominant organism was Escherichia coli, present in 83% of infections. Treatment with sulphonamides produced a good cure rate, which was improved by ampicillin given to failures. Some patients, however, had infections that persisted or recurred despite several antibiotics. The radiological investigations showed that a high proportion of women with asymptomatic urinary infection had severe renal disease which was quite symptomless. This was more pronounced in those with persistent or recurrent infections.     

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.     

Mouse models of short- and long-term foreign body in the urinary bladder: analogies to the bladder segment of urinary catheters.

Catheter-associated bacteriuria is the most common infection occurring in hospitals, where urethral catheters are generally in place for a few days, and in nursing homes, where catheters may be in place for months or years. We developed murine models with intrabladder urinary catheters for studying complications of bacteriuria in short- and long-term catheterization. In the short-term model, a catheter segment was inserted transurethrally and lay free within the bladder lumen. Half of the animals expelled segments during a 2-to-7-day period, durations similar to catheterizations in hospitalized patients. For studies of long-term catheter use, the catheter segment was secured within the bladder by a single suture for up to 12 months. Antibiotics administered for 7 days after catheter placement and housing mice in cages with wire screen floors reduced spontaneous bacteriuria to an acceptably low incidence rate of only 7%. Proteus mirabilis bacteriuria of high concentration provoked the same complications that are common in patients with long-term catheters: acute pyelonephritis, chronic renal inflammation, and struvite stone formation. These models allow inoculation of the bacteria of interest and are suitable for studies of short- and long-term foreign body-associated bacteriuria and its complications.     

Is screening for bacteriuria in pregnancy worth while?

A total of 4470 pregnant women were screened for bacteriuria by the dipslide method and significant growth found in 226 (5.1%). In 198 cases the urine was re-examined, in 119 by using suprapubic aspiration or catheterisation (62 (52%) samples contained bacteria) and in 79 by using midstream urine samples (26 (33%) samples contained greater than 10(8) colony forming units/1), showing the maximum prevalence of confirmed bacteriuria to be 2.6%. Overt urinary tract infection developed later in four of 80 patients with proved bacteriuria who had been given antibiotics, in one of eight untreated patients with bacteriuria, in one of 110 patients with unconfirmed bacteriuria, and in one of 226 non-bacteriuric controls. A history of urinary tract infection was given by 18% of controls and 42% of women with confirmed bacteriuria. Screening for bacteriuria and treatment with antibiotics to prevent later overt infection is expensive. Whether it is worth while and cost effective depends largely on the prevalence of bacteriuria in the local population and the proportion who develop overt infection. The screening and treatment programme reported here appeared to prevent only six cases of overt infection.     

Untreated asymptomatic bacteriuria in girls: I--Stability of urinary isolates.

OBJECTIVE--To assess the frequency of spontaneous changes of bacterial strains in patients with untreated asymptomatic bacteriuria. DESIGN--Retrospective analysis of samples from all patients with renal scarring and random sample of patients with normal kidneys. SETTING--Outpatient clinic for children with urinary tract infections. PATIENTS--54 Girls aged 3.3-15.5 years with untreated asymptomatic bacteriuria caused by Escherichia coli. INTERVENTION--None. END POINT--Change in bacterial strain. MEASUREMENTS AND RESULTS--Serotyping and electrophoretic analysis of sequential bacterial isolates, representing 151 patient years of untreated asymptomatic bacteriuria. A total of 24 changes of strain were identified. Eleven were related to medical interference such as treatment of other infections with antibiotics. CONCLUSIONS--Spontaneous changes of strain were uncommon, one change in 11.6 patient years, and thus are not a characteristic feature of the course of asymptomatic bacteriuria.