1990, 7>K? British Journal of Radiology, 63, 507-511
JULY 1990
VOLUME 63 NUMBER 751
The British Journal of Radiology Review article Urinary tract infection in paediatrics: the role of diagnostic imaging By I. Gordon, FRCR Hospital for Sick Children, Great Ormond Street, London WC1 N 3JH
(Received January 1990)
Infection of the urinary tract (UTI) has several clinical subgroups, each requiring different degrees of investigation. The most severe, acute pyelonephritis, is characterized by ill health, anorexia, pyrexia (>38.5°C), an erythrocyte sedimentation rate greater than 20 mra/h or C-reactive protein greater than 10mg/l, pyuria, bacteruria and possible septicaemia. The child may well require hospitalization and parenteral antibiotics. The term cystitis is used to refer to children with lower urinary tract symptoms but without systemic illness who have more than 100000 bacteria per ml in the urine. They should be distinguished from children who are asymptomatic but nevertheless have positive urine cultures, i.e. asymptomatic bacteruria. This last group usually consists of girls over 5 years old and do not require much investigation. Clinically these three groups overlap to some extent, but nevertheless the presentation should be a guide to the choice of the appropriate imaging.
UTI and in part from renal dysplasia associated with vesico-ureteric reflux (VUR). The probability that any child presenting with UTI is at risk from preventable renal failure is thus less than Haycock's estimate, perhaps six out of a million. Renal damage may result when UTI occurs either in the presence of obstruction, or under certain conditions when VUR is present. Scarring in association with VUR appears to depend on a number of factors: infection, intrarenal reflux and age. The young, especially those under 1 year of age are at greatest risk (Ransley & Risdon, 1975). Scarring in association with VUR is usually apparent at the initial investigation suggesting either that it occurred with the first UTI or that the appearances are a result of dysplasia before the time the child is first seen (Birmingham Reflux Study Group, 1987). The development of new scars has been described, but is rare, especially in the asymptomatic older child (Sherwood & Whitaker, 1984; Smellie et al, 1985). Urinary tract infection in the presence of an obstruction requires surgical treatment.
First proved urinary tract infection
Urinary tract infection is common: the imaging that children undergo is important in terms of resource utilization as well as discomfort and radiation exposure. A conscious effort must be made not to over-investigate the child or to overburden the radiology department, yet treatable disorders or potential long-term complications must be detected (Saxena et al, 1975; Asscher, 1980). Clinical context
A prospective study by Dickson (1979) found 3.1/ 1000 girls and 1.7/1000 boys presented annually with a first symptomatic UTI. The incidence of end-stage renal failure due to pyelonephritis in Europe in individuals under 40 years of age is 4-5 per million per year (Broyer et al, 1984). Combining various data, Haycock (1986) estimated the risk of renal failure due to reflux nephropathy in children presenting with UTI as less than 1% for boys and less than 0.5% for girls. In part this risk arises from pyelonephritic scarring consequent upon Vol. 63, No. 751
Clinical controversy
Most clinicians agree that with UTI and VUR, the age of the child is an important determinant of the risk of scarring. The kidney of young children (under 1 year of age) are most susceptible, whilst in children older than 5 years with normal kidneys, scarring very rarely develops, especially if the child is asymptomatic. The above ages, e.g. 1 and 5 years, are not accepted by all clinicians, some of whom feel that only the kidneys of children less than 2 years of age are at significant risk. One study suggested that only in asymptomatic children over 7 years of age was the risk of scarring with UTI no longer significant (Smellie et al, 1985). The greatest controversy concerns the child between these two age groups: is VUR the major anomaly to be excluded, or should one focus on the kidney? The logic is that if the kidney has not scarred after the first UTI, then it is unlikely to do so later on in this age group, so that the presence or absence of VUR may be unimportant. 507
/. Gordon
Verber et al (1988) and Whyte et al (1988) both showed that it was only worthwhile looking for VUR in children with an abnormal kidney in this intervening age group; conversely there are children in this age group with VUR but without renal scars (White, 1989). Selection of children for imaging
Children of either sex with their first proved UTI require imaging; the younger the child, the more important these investigations. The studies of Williams (1976) and Dickson (1979) have shown that only 18-24% of children with lower urinary tract symptoms actually have UTI, which suggests that the single most important way to avoid unnecessary investigations is to ensure that only those with a definite UTI are investigated. Aims of imaging
Firstly: to diagnose an obstructive uropathy. With increasing use of antenatal ultrasound, many congenital obstructions are diagnosed in utero. This change in medical practice may alter the previous statistics which showed that 10% of children with UTI had an obstructive uropathy. Secondly: to detect the presence of calculi. Thirdly: to identify those children with existing renal damage who are at risk of long-term complications, such as hypertension or chronic renal failure. Fourthly: to identify those children who are at risk of developing renal damage. Finally: to monitor progress and the results of surgery. Imaging controversy
Classically the diagnosis of renal scarring was based on the intravenous urogram (IVU) and that of VUR on contrast micturating cystourethrography (MCUG). Newer imaging techniques with lower degrees of invasiveness are widely available, and their role is being constantly appraised. There is little value in comparing a high quality IVU with an inadequate abdominal ultrasound (US) examination or "Tcm dimercaptosuccinic acid (DMSA) scan. It is the responsibility of radiologists to ensure that good techniques (e.g. US, radionuclide cystography or "Tcm DMSA scanning) do not develop bad reputations because of poor quality examinations. This article connot attempt to cover comprehensively imaging of the paediatric renal tract. It will focus on certain important aspects of each technique. Ultrasound should diagnose all cases of obstructive uropathy, the majority of calculi and the presence of a small kidney. Renal length can be measured accurately by US in the majority of children and longitudinal examinations provide evidence of renal growth. A full US examination includes views of the bladder and the area behind the bladder. It is prudent to begin the US examination with views of the bladder in the younger child since micturition may occur during the examination, preventing evaluation of the lower ureters later. Numerous studies have shown the high sensitivity and specificity of US as a screening procedure for children 508
with UTI compared with the IVU (Jaquier et al, 1983; Sherwood & Whitaker, 1984; Kangarloo et al, 1985; Whyte et al, 1988). If scarring is detected on US then there is no reason to doubt its existence but a normal US does not exclude a renal scar. The IVU in children under 2 years of age may not provide sufficient anatomical detail, since high quality radiographs are difficult to obtain. The presence of bowel gas may obscure the calyces. Thus it is important to ensure quality of the US and "Tcm DMSA scans. A recent survey showed that 76% of paediatricians in England had access to radionuclide facilities but the survey implied that this facility was not fully used (Smyth et al, 1988). The "Tcm DMSA scan is a sensitive technique to detect a renal scar; recent studies support the early impression of the high sensitivity of the "Tcm DMSA in the detection of a renal scar (Merrick et al, 1980; Stroller & Kogan, 1986; Goldraich et al, 1989). The initial IVU missed most of the scarring compared with "TcmDMSA in children between 0 and 6 years (Goldraich et al, 1989). This not surprising considering that this is the age when it is most difficult to obtain a high quality IVU. Most studies show that the "TcmDMSA scan does have a false negative rate (Smellie et al, 1988), but this is small compared with the false negative rate for the IVU. The time necessary for the development of a renal scar is unclear; using the IVU the shortest time recorded is 8-9 months, by Smellie et al (1975) and Hugosson et al (1976). Hodson and Wilson (1965) suggested that bipolar scarring took 16 months to develop, while Filly et al (1974) suggested that 2 years could be required in certain cases. Using "Tcm DMSA, Monsour et al (1987) showed that 25% of kidneys had photon-deficient areas if scanned during the first month after the UTI, while at 6 months only 4% still had defects which could now be called scars, and Goldraich et al (1989) found that "TcmDMSA scans in five children with UTI were abnormal during the infection but only one remained abnormal 4 weeks later. Parkhouse et al (1989) showed a similar time course in experimental UTI in the pig using "TcmDMSA. However, Verber et al (1988) found that 80% of all defects remain unchanged on follow-up "TcmDMSA scan in a selected group of children. It seems that "TcmDMSA scans show scars earlier than IVU, but should not be done within 4 weeks of the UTI. The MCUG has been suggested as the first line imaging investigation in UTI (Blickman et al, 1985), but the information provided is restricted to the bladder, bladder emptying and VUR. Some clinicians state that the urethra in boys must be visualized in order to exclude bladder outlet obstruction, yet no study has compared the results of a comprehensive US examination (including full and empty bladder views) with the results of MCUG in the same boys. Renal reflux may be detected using radionuclide cystography with a reduction of radiation exposure by a factor of 20 compared with the MCUG (Rothwell et al, 1977). In the toilet trained child an indirect radionuclide cystogram (IRC), without the need for bladder catheterization, can be The British Journal of Radiology, July 1990
The role of diagnostic imaging in paediatric UTI
carried out using "Tcm mercapto acetyl triglycine ("Tcm M AG3), when inclusion of the dynamic phase of the renal scan provides information on individual kidney function. If the volume and radioactivity of the voided urine is measured, the IRC can provide premicturition bladder volume, residual volume, peak flow rate and, if renal reflux is seen, this can be quantified (van der Vis-Melsen et al, 1989). In the younger child (i.e. not toilet trained) a direct radionuclide cystogram (DRC) which requires a bladder catheter (a procedure similar to the classical MCUG) may be undertaken. The results of the DRC may also be quantified (Willi & Treves, 1985). The DRC has a high sensitivity compared with the MCUG (Conway & Kruglik, 1976; Willi & Treves, 1985), as does the IRC (Handmaker et al, 1973; Pollet et al, 1981; Bower et al, 1985; Nielsen et al, 1985; Carlsen et al, 1986; Chapman et al, 1988). Few studies have been reported with poor results of the IRC (Majd, 1986). Radioisotopic imaging procedures do not increase radiation exposure. Time is required before full assessment of any new technique can take place. The US images are best interpreted by the radiologist who did the examination, particularly as lack of anatomical landmarks adds difficulty to remote interpretation. Radionuclides provide functional information in the form of both images and numbers/graphs. Radiological anatomical detail is lacking and therefore certain clinicians are sceptical in accepting the high sensitivity of the gamma camera in detecting small abnormalities. These factors add to the hesitation some radiologists and clinicians feel towards either US and/or radionuclide studies. An increasing number of articles suggest that in institutions with high quality US and radioisotope facilities, the well trusted IVU and MCUG may be displaced as first line investigations in certain children with a UTI. A possible result is over-investigation of children with UTI (Whyte et al, 1988). Medical audit is now an accepted concept, which
Table I
FIRST PROVED UTI NORMAL AGE 1 YEAR
ULTRASOUND AGE > 5 YEARS
AGE 1-5 YEARS
"Tcm DMSA + CYSTOGRAM I REFLUX
"Tcm DMSA
STOP
NORMAL
FOLLOW-UP
FOCAL DEFECT
CYSTOGRAM
STOP
with divergent approaches between radiologists about investigation of UTI, should allow assessment of different imaging techniques and responsible use of resources (Diament, 1988). An example is the value of the plain abdominal film in children under 2 years of age, which is considered by some paediatric radiologists to be essential, yet there is no study validating this point. Preliminary results of a study at four paediatric centres in Britain suggest that no significant urological or skeletal abnormality would have been missed in over 600 children of all ages if the plain abdominal radiograph had been excluded from the initial imaging sequence (Kenney, 1989). Mention has been made of the different quality of certain investigations: surely it is up to radiologists (including US, nuclear medicine, etc.) as a group to ensure that all the examinations done are diagnostic!
Table III
FIRST PROVED UTI ABDOMINAL ULTRASOUND +
ABDOMINAL RADIOGRAPH
NORMAL RESULT
ABNORMAL RESULT
FIRST PROVED UTI ABNORMAL WITH HYDRONEPHROSIS I "Tcm DIURETIC MAG3 + CYSTOGRAM
OBSTRUCTION SEE TABLE
ULTRASOUND I WITHOUT HYDRONEPHROSIS I "Tcm DMSA + CYSTOGRAM
NO REFLUX
SEE TABLE IVU
Vol. 63, No. 751
REFLUX FOLLOW-UP
509
/. Gordon Protocol for the first documented UTI (Tables I—III)
The purpose of a protocol is to focus the attention of the medical team to ensure that the protocol fits the child and not that the child is forced tofitthe protocol. Currently all children with UTI shoud have a plain abdominal radiograph as well as an US of the kidneys and bladder to exclude urinary calculi, nephrocalcinosis and obstructive uropathy, as well as to measure the renal size (Jaquier et al, 1983; Sherwood & Whitaker, 1984; Kangarloo et al, 1985; Whyte et al, 1980). If the US is normal then no further investigations should be undertaken in children older than 5 years. The susceptibility of the kidney to damage from VUR and UTI in infants under 1 year old means that both VUR and renal scars should be positively excluded. This requires both a cystogram and "TcmDMSA scan. In girls, a DRC may be carried out, but in boys, a MCUG is required. In the child between 1 and 5 years of age there is no general agreement. One suggested pathway is a "Tcm DMSA at 1-4 months after the UTI to identify an abnormal kidney; if abnormal the child requires a cystogram. If the "TcmDMSA is normal then it is appropriate to wait for any second UTI before undertaking further investigation. An alternative pathway is to carry out a cystogram, and then stop if no VUR is detected; if VUR is seen then a "Tcm DMSA scan would be required to assess the extent of any renal damage. Vesico-ureteric reflux should be excluded in infants with a family history of VUR or reflux nephropathy. This should be done in the neonatal period before any UTI has occurred. If VUR is detected then a "TcmDMSA scan should be undertaken at about 3 months of age while the infant is on a prophylactic urinary antiseptic. If a "Tcm DMSA scan is carried out at a younger age, renal immaturity may make detection of scars difficult. Long-term follow-up
All children with VUR and an abnormal kidney require long-term follow-up irrespective of their age because of the increased incidence of hypertension and the occasional development of chronic renal failure. Many children with VUR will be placed on long-term antibiotic prophylaxis; if cessation of VUR is a prerequisite to stop this treatment then re-evaluation for VUR should be done with a radioisotope cystogram (either DRC in the younger child or IRC in the toilet trained child). If ureteric reimplantation has been undertaken then an US and 99TcmMAG3 isotope scan are required to exclude obstruction following surgery, and to show that renal reflux has been prevented. Children with a scarred kidney require regular blood pressure monitoring with infrequent but regular imaging. Recurrent or breakthrough symptomatic UTI
If US has shown that both kidneys are normal, then in older children (more than 5 years), the possibility of renal damage is very small (Smellie et al, 1985) and further imaging is that of a second UTI, i.e a repeat 510
comprehensive US (including images of the bladder preand post-micturition) and an IRC (assessing renal function excluding renal reflux). With a further symptomatic UTI then an IVU with another comprehensive US should be done to exclude unusual pathology. The younger child (between 1 and 5 years) with normal kidneys and known VUR requires a repeat cystogram to assess if the reflux has stopped since some clinicians will consider surgery to stop VUR (reimplantation or periureteric injection therapy, i.e. "Sting") in this situation. The younger the child, the more inclined one would be to repeat the "Tcm DMSA in the presence of VUR and breakthrough infection. Progressive renal damage in previously scarred kidneys has been well documented. Verber and Meller (1988) showed that all children with progressive renal damage had breakthrough infections in the presence of VUR. These infections require prompt treatment and require that the child returns to the radiology department for further imaging to assess the VUR and the extent of the renal damage on "Tcm DMSA. Acute phylonephritis
This manifestation of UTI requires imaging of both the upper and lower renal tract. The US may show a large "bright" kidney compared with the opposite side, or may be normal (Christophe et al, 1983). On the "TcmDMSA scan the entire kidney functions poorly with additional photon deficient areas. Computerized tomography (CT) shows a large kidney with no enhancement of focally affected areas following intravenous contrast medium. Progress of the condition should be monitored by US with either "TcmDMSA scan or CT scan. The use of the IVU has been rather disappointing. Reflux must be positively excluded; in girls a radioisotope cystogram is sufficient while in boys, the urologist who demands to see the urethra will press for a MCUG. Conclusion
The first proved UTI in any child requires investigation. All children should have a US and plain abdominal radiograph. Children under 1 year of age also require a MCUG and "Tcm DMSA scan. Children over 5 years of age do not require further imaging. Children aged between 1 and 5 years require a "Tcm DMSA scan and/or a cystogram, with choice of procedure currently varying with different clinical opinions. All follow-up cystography for VUR should be with radionuclides. References ASSCHER, W. A., 1980. Sequelae of Urinary Tract Infection. The Challenge of Urinary Tract Infections (Academic Press, London), pp. 112-128. BIRMINGHAM REFLUX STUDY GROUP, 1987. Prospective trial of
operative versus non-operative treatment of severe reflux in childhood: five years' observation. British Medical Journal, 295, 237-241. BLICKMAN, J. G., TAYLOR, G. A. & LOBOWITZ, R. L., 1985.
Voiding cystourethrography: the initial radiologic study in children with urinary tract infection. Radiology, 156, 659-662.
The British Journal of Radiology, July 1990
The role of diagnostic imaging in paediatric UTI BOWER, G., LOVEGROVE, F. T., GEIJSEL, H., VAN DER SCAFF, A.
NIELSEN, J. B., JENSEN, F. T., MUNCH, J. T., CHARLES, P. &
& GUELFI, G., 1985. Comparison of direct and indirect radionuclide cystography. Journal of Nuclear Medicine, 26, 465^68.
DJURHUIS, J. C , 1985. The diagnosis of vesico-ureteral reflux. Radiologic and medicine methods. Scandinavian Journal of Urology and Nephrology, 19, 109-112.
BROYER, M., RIZZONI, G., BRUNNER, F. P., BRYNGER, H., CHALLAH, S., GRETY, N., JACOBS, C , KRAMER, P., SELWOOD,
PARKHOUSE, H. F., GODLEY, M. L., COOPER, J., RISDON, R. A.
N. H. & WING, A. J., 1984. Combined report on regular dialysis and transplantation of children in Europe. XIV Proceedings of the European Dialysis and Transplant Association, 5, 55—79. CARLSEN, O., LUKMAN, B. & NATHAN, E.,
1986. Indirect
radionuclide renocystography for determination of vesicoureteral reflux in children. European Journal of Nuclear Medicine, 12, 205-210. CHAPMAN, S. J., CHANTLER, C , HAYCOCK, G. B., MAISEY, M.
N. & SAXTON, H. M., 1988. Radionuclide cystography in vesico-ureteric reflux. Archives of Disease in Childhood, 63, 650-651.
& RANSLEY, P. G., 1989. Renal imaging with Tc 99m DMSA in the detection of acute pyelonephritis: an experimental study in the pig. Nuclear Medicine Communications, 10, 63-70. POLLET, J. E., SHARP, P. F., SMITH, F. W., DAVIDSON, A. I. &
MILLER, S. S., 1981. Intravenous radionclide cystography for the detection of vesico-renal reflux. Journal of Urology, 125, 75-78. RANSLEY, P. G. & RISDON, R. A., 1975. Papillary morphology
in infants 111-113.
and young children.
Urology Research, 3,
ROTHWELL, D. L., CONSTABLE, A. R., & ALBRECHT, M., 1977.
KRAMER-
Radionuclide cystography in the investigation of vesicoureteric reflux in children. Lancet, i, 1072-1075.
of pyelonephritis.
SAXENA, S. R., LAWRENCE, B. M. & SHAW, D. G., 1975. The
CONWAY, J. J. & KRUGLIK, G. D., 1976. Effectiveness of direct
justification for early radiological investigation of urinary tract in children. Lancet, ii, 403.
CHRISTOPHE,
C,
BOGAERT,
C,
SPEHL,
PERMULTER, N., 1983. Ultrasound Pediatrics, 13, 173.
M.
&
and indirect radionuclide cystography in detecting vesicoureteral reflux. Journal of Nuclear Medicine, 17, 81-83. DIAMENT, M. J., 1988. Is ultrasound screening for urinary tract infection cost effective? Pediatric Radiology, 18, 157-159. DICKSON, J. A., 1979. Incidence and outcome of symptomatic urinary tract infection in children. British Medical Journal, i, 1330-1332.
SHERWOOD, T. & WHITAKER, R. H., 1984. Initial screening of
children with urinary tract radiography and ultrasound Journal, 288, 827.
infections: is plain film enough? British Medical
SMELLIE, J. M., EDWARDS, D., HUNTER, N., NORMAND, I. C. S.
& PRESCOD, N., 1975. Vesico-ureteric reflux and renal scarring. Kidney International, 8, s65-s72.
FILLY, R. A., FRIEDLAND, G. W., GOVEN, D. E. & FAIR, W. R.,
SMELLIE, J. M., RANSLEY, P. G., NORMAND, I. C. S., PRESCOD,
1974. Development and progression of clubbing and scarring in children with recurrent urinary tract infection. Radiology, 113, 145-153.
N. & EDWARDS, D., 1985. Development of new renal scars: a collaborative study. British Medical Journal, 290, 1957-1960.
GOLDRAICH, N. P., RAMOS, O. L. & GOLDRAICH, I. H., 1989.
Urography versus DMSA scan in children with vesicoureteric reflux. Pediatric Nephrology, 3, 1-5. HAYCOCK, G. B., 1986. Investigation of urinary tract infection. Archives of Disease in Childhood, 12, 1155-1158. HANDMAKER, H., MCRAE, J. & BUCK, E. G., 1973. Intravenous
radionuclide voiding cystography (IRVC). Radiology, 108, 703-705. HODSON, C. J. & WILSON, S., 1965. Natural history of chronic pyelonephritic scarring. British Medical Journal, 2, 191-194. HUGOSSON, C. O., CHRISPIN, A. R. & WOLVERSON, M. K., 1976.
The advent of the pyelonephrotic scar. Annals of Radiology, 19, 1-6. JAQUIER, S., BORGES, M., FORBES, P. & NOGRADY, M. B., 1983.
The value of ultrasound examination as a screening procedure in first documented urinary tract infection in children. Pediatric Radiology, 13, 173. KANGARLOO, H., GOLD, R. H., FINE, R. N. & DIAMENT, M. J.,
1985. Urinary tract infection in infants and children evaluated by ultrasound. Radiology, 155, 367-374. KENNEY, I., 1989. Personal communication. MAJD, M., 1986. Comparison of direct and indirect isotope cystography. Radiology, 158, 228. MERRICK, M., UTTLEY, W. S. & WILD, S. R.,
1980. The
detection of pyelonephritic scarring in children by isotope imaging. British Journal of Radiology, 53, 544-556. MONSOUR, M., AZMY, A. F. & MACKENZIE, J. R., 1987. Renal
scarring secondary to VUR. Critical assessment and new grading. British Journal of Urology, 60, 320-324.
Vol. 63, No. 751
SMELLIE, J. M., SHAW, P. J., PRESCOD, N. P. & BANTOCK, H.
M., 1988. 99m Tc DMSA scan in patients with established radiological scarring. Archives of Disease in Childhood, 63, 1315-1319. SMYTH, R. L., BERMAN, L. & VALMAN, H. B., 1988. Current
practice in managing urinary tract infection in children. British Medical Journal, 297, 1516-1517. STROLLER,
M.
L. & KOGAN,
B. A.,
1986. Sensitivity
of
Tc 99m DMSA for the diagnosis of chronic pyelonephritis: Clinical and theoretical considerations. Journal of Urology, 135, 977-980. VAN DER VlS-MELSEN, M. J. E., BAERT, R. J. M., RAJNHERC, J. R. et al, 1989. Scintigraphic assessment of lower urinary tract function in children with and without outflow tract obstruction. British Journal of Urology, 64, 263-269. VERBER, I. G., STRUDLEY, M. R. & MELLER, S. T., 1988.
99m Tc DMSA scan as first investigation of urinary tract infection. Archives of Disease in Childhood, 63, 1302-1325. WHITE, R. H. R., 1989. Vesicoureteric reflux and renal scarring. Archives of Disease in Childhood, 64, 407-412. WHYTE, K. M., ABBOT, G. D., KENNEDY, J. C. & MALING, T.
M. J., 1988. A protocol for the investigation of infants and children with urinary tract infection. Clinical Radiology, 39, 278-280. WILLIAMS, C. M., 1976. Urinary tract infection in children: general practice survey. Aust. Fam. Physician, 5, 340-344. WILLI, U. V. & TREVES, S. T., 1985. Radionuclide voiding
cystography. In Paediatric Nuclear Medicine, ed. by S. T. Treves, (Springer-Verlag, New York), p. 105.
511
JULY 1990
VOLUME 63 NUMBER 751
The British Journal of Radiology Review article Urinary tract infection in paediatrics: the role of diagnostic imaging By I. Gordon, FRCR Hospital for Sick Children, Great Ormond Street, London WC1 N 3JH
(Received January 1990)
Infection of the urinary tract (UTI) has several clinical subgroups, each requiring different degrees of investigation. The most severe, acute pyelonephritis, is characterized by ill health, anorexia, pyrexia (>38.5°C), an erythrocyte sedimentation rate greater than 20 mra/h or C-reactive protein greater than 10mg/l, pyuria, bacteruria and possible septicaemia. The child may well require hospitalization and parenteral antibiotics. The term cystitis is used to refer to children with lower urinary tract symptoms but without systemic illness who have more than 100000 bacteria per ml in the urine. They should be distinguished from children who are asymptomatic but nevertheless have positive urine cultures, i.e. asymptomatic bacteruria. This last group usually consists of girls over 5 years old and do not require much investigation. Clinically these three groups overlap to some extent, but nevertheless the presentation should be a guide to the choice of the appropriate imaging.
UTI and in part from renal dysplasia associated with vesico-ureteric reflux (VUR). The probability that any child presenting with UTI is at risk from preventable renal failure is thus less than Haycock's estimate, perhaps six out of a million. Renal damage may result when UTI occurs either in the presence of obstruction, or under certain conditions when VUR is present. Scarring in association with VUR appears to depend on a number of factors: infection, intrarenal reflux and age. The young, especially those under 1 year of age are at greatest risk (Ransley & Risdon, 1975). Scarring in association with VUR is usually apparent at the initial investigation suggesting either that it occurred with the first UTI or that the appearances are a result of dysplasia before the time the child is first seen (Birmingham Reflux Study Group, 1987). The development of new scars has been described, but is rare, especially in the asymptomatic older child (Sherwood & Whitaker, 1984; Smellie et al, 1985). Urinary tract infection in the presence of an obstruction requires surgical treatment.
First proved urinary tract infection
Urinary tract infection is common: the imaging that children undergo is important in terms of resource utilization as well as discomfort and radiation exposure. A conscious effort must be made not to over-investigate the child or to overburden the radiology department, yet treatable disorders or potential long-term complications must be detected (Saxena et al, 1975; Asscher, 1980). Clinical context
A prospective study by Dickson (1979) found 3.1/ 1000 girls and 1.7/1000 boys presented annually with a first symptomatic UTI. The incidence of end-stage renal failure due to pyelonephritis in Europe in individuals under 40 years of age is 4-5 per million per year (Broyer et al, 1984). Combining various data, Haycock (1986) estimated the risk of renal failure due to reflux nephropathy in children presenting with UTI as less than 1% for boys and less than 0.5% for girls. In part this risk arises from pyelonephritic scarring consequent upon Vol. 63, No. 751
Clinical controversy
Most clinicians agree that with UTI and VUR, the age of the child is an important determinant of the risk of scarring. The kidney of young children (under 1 year of age) are most susceptible, whilst in children older than 5 years with normal kidneys, scarring very rarely develops, especially if the child is asymptomatic. The above ages, e.g. 1 and 5 years, are not accepted by all clinicians, some of whom feel that only the kidneys of children less than 2 years of age are at significant risk. One study suggested that only in asymptomatic children over 7 years of age was the risk of scarring with UTI no longer significant (Smellie et al, 1985). The greatest controversy concerns the child between these two age groups: is VUR the major anomaly to be excluded, or should one focus on the kidney? The logic is that if the kidney has not scarred after the first UTI, then it is unlikely to do so later on in this age group, so that the presence or absence of VUR may be unimportant. 507
/. Gordon
Verber et al (1988) and Whyte et al (1988) both showed that it was only worthwhile looking for VUR in children with an abnormal kidney in this intervening age group; conversely there are children in this age group with VUR but without renal scars (White, 1989). Selection of children for imaging
Children of either sex with their first proved UTI require imaging; the younger the child, the more important these investigations. The studies of Williams (1976) and Dickson (1979) have shown that only 18-24% of children with lower urinary tract symptoms actually have UTI, which suggests that the single most important way to avoid unnecessary investigations is to ensure that only those with a definite UTI are investigated. Aims of imaging
Firstly: to diagnose an obstructive uropathy. With increasing use of antenatal ultrasound, many congenital obstructions are diagnosed in utero. This change in medical practice may alter the previous statistics which showed that 10% of children with UTI had an obstructive uropathy. Secondly: to detect the presence of calculi. Thirdly: to identify those children with existing renal damage who are at risk of long-term complications, such as hypertension or chronic renal failure. Fourthly: to identify those children who are at risk of developing renal damage. Finally: to monitor progress and the results of surgery. Imaging controversy
Classically the diagnosis of renal scarring was based on the intravenous urogram (IVU) and that of VUR on contrast micturating cystourethrography (MCUG). Newer imaging techniques with lower degrees of invasiveness are widely available, and their role is being constantly appraised. There is little value in comparing a high quality IVU with an inadequate abdominal ultrasound (US) examination or "Tcm dimercaptosuccinic acid (DMSA) scan. It is the responsibility of radiologists to ensure that good techniques (e.g. US, radionuclide cystography or "Tcm DMSA scanning) do not develop bad reputations because of poor quality examinations. This article connot attempt to cover comprehensively imaging of the paediatric renal tract. It will focus on certain important aspects of each technique. Ultrasound should diagnose all cases of obstructive uropathy, the majority of calculi and the presence of a small kidney. Renal length can be measured accurately by US in the majority of children and longitudinal examinations provide evidence of renal growth. A full US examination includes views of the bladder and the area behind the bladder. It is prudent to begin the US examination with views of the bladder in the younger child since micturition may occur during the examination, preventing evaluation of the lower ureters later. Numerous studies have shown the high sensitivity and specificity of US as a screening procedure for children 508
with UTI compared with the IVU (Jaquier et al, 1983; Sherwood & Whitaker, 1984; Kangarloo et al, 1985; Whyte et al, 1988). If scarring is detected on US then there is no reason to doubt its existence but a normal US does not exclude a renal scar. The IVU in children under 2 years of age may not provide sufficient anatomical detail, since high quality radiographs are difficult to obtain. The presence of bowel gas may obscure the calyces. Thus it is important to ensure quality of the US and "Tcm DMSA scans. A recent survey showed that 76% of paediatricians in England had access to radionuclide facilities but the survey implied that this facility was not fully used (Smyth et al, 1988). The "Tcm DMSA scan is a sensitive technique to detect a renal scar; recent studies support the early impression of the high sensitivity of the "Tcm DMSA in the detection of a renal scar (Merrick et al, 1980; Stroller & Kogan, 1986; Goldraich et al, 1989). The initial IVU missed most of the scarring compared with "TcmDMSA in children between 0 and 6 years (Goldraich et al, 1989). This not surprising considering that this is the age when it is most difficult to obtain a high quality IVU. Most studies show that the "TcmDMSA scan does have a false negative rate (Smellie et al, 1988), but this is small compared with the false negative rate for the IVU. The time necessary for the development of a renal scar is unclear; using the IVU the shortest time recorded is 8-9 months, by Smellie et al (1975) and Hugosson et al (1976). Hodson and Wilson (1965) suggested that bipolar scarring took 16 months to develop, while Filly et al (1974) suggested that 2 years could be required in certain cases. Using "Tcm DMSA, Monsour et al (1987) showed that 25% of kidneys had photon-deficient areas if scanned during the first month after the UTI, while at 6 months only 4% still had defects which could now be called scars, and Goldraich et al (1989) found that "TcmDMSA scans in five children with UTI were abnormal during the infection but only one remained abnormal 4 weeks later. Parkhouse et al (1989) showed a similar time course in experimental UTI in the pig using "TcmDMSA. However, Verber et al (1988) found that 80% of all defects remain unchanged on follow-up "TcmDMSA scan in a selected group of children. It seems that "TcmDMSA scans show scars earlier than IVU, but should not be done within 4 weeks of the UTI. The MCUG has been suggested as the first line imaging investigation in UTI (Blickman et al, 1985), but the information provided is restricted to the bladder, bladder emptying and VUR. Some clinicians state that the urethra in boys must be visualized in order to exclude bladder outlet obstruction, yet no study has compared the results of a comprehensive US examination (including full and empty bladder views) with the results of MCUG in the same boys. Renal reflux may be detected using radionuclide cystography with a reduction of radiation exposure by a factor of 20 compared with the MCUG (Rothwell et al, 1977). In the toilet trained child an indirect radionuclide cystogram (IRC), without the need for bladder catheterization, can be The British Journal of Radiology, July 1990
The role of diagnostic imaging in paediatric UTI
carried out using "Tcm mercapto acetyl triglycine ("Tcm M AG3), when inclusion of the dynamic phase of the renal scan provides information on individual kidney function. If the volume and radioactivity of the voided urine is measured, the IRC can provide premicturition bladder volume, residual volume, peak flow rate and, if renal reflux is seen, this can be quantified (van der Vis-Melsen et al, 1989). In the younger child (i.e. not toilet trained) a direct radionuclide cystogram (DRC) which requires a bladder catheter (a procedure similar to the classical MCUG) may be undertaken. The results of the DRC may also be quantified (Willi & Treves, 1985). The DRC has a high sensitivity compared with the MCUG (Conway & Kruglik, 1976; Willi & Treves, 1985), as does the IRC (Handmaker et al, 1973; Pollet et al, 1981; Bower et al, 1985; Nielsen et al, 1985; Carlsen et al, 1986; Chapman et al, 1988). Few studies have been reported with poor results of the IRC (Majd, 1986). Radioisotopic imaging procedures do not increase radiation exposure. Time is required before full assessment of any new technique can take place. The US images are best interpreted by the radiologist who did the examination, particularly as lack of anatomical landmarks adds difficulty to remote interpretation. Radionuclides provide functional information in the form of both images and numbers/graphs. Radiological anatomical detail is lacking and therefore certain clinicians are sceptical in accepting the high sensitivity of the gamma camera in detecting small abnormalities. These factors add to the hesitation some radiologists and clinicians feel towards either US and/or radionuclide studies. An increasing number of articles suggest that in institutions with high quality US and radioisotope facilities, the well trusted IVU and MCUG may be displaced as first line investigations in certain children with a UTI. A possible result is over-investigation of children with UTI (Whyte et al, 1988). Medical audit is now an accepted concept, which
Table I
FIRST PROVED UTI NORMAL AGE 1 YEAR
ULTRASOUND AGE > 5 YEARS
AGE 1-5 YEARS
"Tcm DMSA + CYSTOGRAM I REFLUX
"Tcm DMSA
STOP
NORMAL
FOLLOW-UP
FOCAL DEFECT
CYSTOGRAM
STOP
with divergent approaches between radiologists about investigation of UTI, should allow assessment of different imaging techniques and responsible use of resources (Diament, 1988). An example is the value of the plain abdominal film in children under 2 years of age, which is considered by some paediatric radiologists to be essential, yet there is no study validating this point. Preliminary results of a study at four paediatric centres in Britain suggest that no significant urological or skeletal abnormality would have been missed in over 600 children of all ages if the plain abdominal radiograph had been excluded from the initial imaging sequence (Kenney, 1989). Mention has been made of the different quality of certain investigations: surely it is up to radiologists (including US, nuclear medicine, etc.) as a group to ensure that all the examinations done are diagnostic!
Table III
FIRST PROVED UTI ABDOMINAL ULTRASOUND +
ABDOMINAL RADIOGRAPH
NORMAL RESULT
ABNORMAL RESULT
FIRST PROVED UTI ABNORMAL WITH HYDRONEPHROSIS I "Tcm DIURETIC MAG3 + CYSTOGRAM
OBSTRUCTION SEE TABLE
ULTRASOUND I WITHOUT HYDRONEPHROSIS I "Tcm DMSA + CYSTOGRAM
NO REFLUX
SEE TABLE IVU
Vol. 63, No. 751
REFLUX FOLLOW-UP
509
/. Gordon Protocol for the first documented UTI (Tables I—III)
The purpose of a protocol is to focus the attention of the medical team to ensure that the protocol fits the child and not that the child is forced tofitthe protocol. Currently all children with UTI shoud have a plain abdominal radiograph as well as an US of the kidneys and bladder to exclude urinary calculi, nephrocalcinosis and obstructive uropathy, as well as to measure the renal size (Jaquier et al, 1983; Sherwood & Whitaker, 1984; Kangarloo et al, 1985; Whyte et al, 1980). If the US is normal then no further investigations should be undertaken in children older than 5 years. The susceptibility of the kidney to damage from VUR and UTI in infants under 1 year old means that both VUR and renal scars should be positively excluded. This requires both a cystogram and "TcmDMSA scan. In girls, a DRC may be carried out, but in boys, a MCUG is required. In the child between 1 and 5 years of age there is no general agreement. One suggested pathway is a "Tcm DMSA at 1-4 months after the UTI to identify an abnormal kidney; if abnormal the child requires a cystogram. If the "TcmDMSA is normal then it is appropriate to wait for any second UTI before undertaking further investigation. An alternative pathway is to carry out a cystogram, and then stop if no VUR is detected; if VUR is seen then a "Tcm DMSA scan would be required to assess the extent of any renal damage. Vesico-ureteric reflux should be excluded in infants with a family history of VUR or reflux nephropathy. This should be done in the neonatal period before any UTI has occurred. If VUR is detected then a "TcmDMSA scan should be undertaken at about 3 months of age while the infant is on a prophylactic urinary antiseptic. If a "Tcm DMSA scan is carried out at a younger age, renal immaturity may make detection of scars difficult. Long-term follow-up
All children with VUR and an abnormal kidney require long-term follow-up irrespective of their age because of the increased incidence of hypertension and the occasional development of chronic renal failure. Many children with VUR will be placed on long-term antibiotic prophylaxis; if cessation of VUR is a prerequisite to stop this treatment then re-evaluation for VUR should be done with a radioisotope cystogram (either DRC in the younger child or IRC in the toilet trained child). If ureteric reimplantation has been undertaken then an US and 99TcmMAG3 isotope scan are required to exclude obstruction following surgery, and to show that renal reflux has been prevented. Children with a scarred kidney require regular blood pressure monitoring with infrequent but regular imaging. Recurrent or breakthrough symptomatic UTI
If US has shown that both kidneys are normal, then in older children (more than 5 years), the possibility of renal damage is very small (Smellie et al, 1985) and further imaging is that of a second UTI, i.e a repeat 510
comprehensive US (including images of the bladder preand post-micturition) and an IRC (assessing renal function excluding renal reflux). With a further symptomatic UTI then an IVU with another comprehensive US should be done to exclude unusual pathology. The younger child (between 1 and 5 years) with normal kidneys and known VUR requires a repeat cystogram to assess if the reflux has stopped since some clinicians will consider surgery to stop VUR (reimplantation or periureteric injection therapy, i.e. "Sting") in this situation. The younger the child, the more inclined one would be to repeat the "Tcm DMSA in the presence of VUR and breakthrough infection. Progressive renal damage in previously scarred kidneys has been well documented. Verber and Meller (1988) showed that all children with progressive renal damage had breakthrough infections in the presence of VUR. These infections require prompt treatment and require that the child returns to the radiology department for further imaging to assess the VUR and the extent of the renal damage on "Tcm DMSA. Acute phylonephritis
This manifestation of UTI requires imaging of both the upper and lower renal tract. The US may show a large "bright" kidney compared with the opposite side, or may be normal (Christophe et al, 1983). On the "TcmDMSA scan the entire kidney functions poorly with additional photon deficient areas. Computerized tomography (CT) shows a large kidney with no enhancement of focally affected areas following intravenous contrast medium. Progress of the condition should be monitored by US with either "TcmDMSA scan or CT scan. The use of the IVU has been rather disappointing. Reflux must be positively excluded; in girls a radioisotope cystogram is sufficient while in boys, the urologist who demands to see the urethra will press for a MCUG. Conclusion
The first proved UTI in any child requires investigation. All children should have a US and plain abdominal radiograph. Children under 1 year of age also require a MCUG and "Tcm DMSA scan. Children over 5 years of age do not require further imaging. Children aged between 1 and 5 years require a "Tcm DMSA scan and/or a cystogram, with choice of procedure currently varying with different clinical opinions. All follow-up cystography for VUR should be with radionuclides. References ASSCHER, W. A., 1980. Sequelae of Urinary Tract Infection. The Challenge of Urinary Tract Infections (Academic Press, London), pp. 112-128. BIRMINGHAM REFLUX STUDY GROUP, 1987. Prospective trial of
operative versus non-operative treatment of severe reflux in childhood: five years' observation. British Medical Journal, 295, 237-241. BLICKMAN, J. G., TAYLOR, G. A. & LOBOWITZ, R. L., 1985.
Voiding cystourethrography: the initial radiologic study in children with urinary tract infection. Radiology, 156, 659-662.
The British Journal of Radiology, July 1990
The role of diagnostic imaging in paediatric UTI BOWER, G., LOVEGROVE, F. T., GEIJSEL, H., VAN DER SCAFF, A.
NIELSEN, J. B., JENSEN, F. T., MUNCH, J. T., CHARLES, P. &
& GUELFI, G., 1985. Comparison of direct and indirect radionuclide cystography. Journal of Nuclear Medicine, 26, 465^68.
DJURHUIS, J. C , 1985. The diagnosis of vesico-ureteral reflux. Radiologic and medicine methods. Scandinavian Journal of Urology and Nephrology, 19, 109-112.
BROYER, M., RIZZONI, G., BRUNNER, F. P., BRYNGER, H., CHALLAH, S., GRETY, N., JACOBS, C , KRAMER, P., SELWOOD,
PARKHOUSE, H. F., GODLEY, M. L., COOPER, J., RISDON, R. A.
N. H. & WING, A. J., 1984. Combined report on regular dialysis and transplantation of children in Europe. XIV Proceedings of the European Dialysis and Transplant Association, 5, 55—79. CARLSEN, O., LUKMAN, B. & NATHAN, E.,
1986. Indirect
radionuclide renocystography for determination of vesicoureteral reflux in children. European Journal of Nuclear Medicine, 12, 205-210. CHAPMAN, S. J., CHANTLER, C , HAYCOCK, G. B., MAISEY, M.
N. & SAXTON, H. M., 1988. Radionuclide cystography in vesico-ureteric reflux. Archives of Disease in Childhood, 63, 650-651.
& RANSLEY, P. G., 1989. Renal imaging with Tc 99m DMSA in the detection of acute pyelonephritis: an experimental study in the pig. Nuclear Medicine Communications, 10, 63-70. POLLET, J. E., SHARP, P. F., SMITH, F. W., DAVIDSON, A. I. &
MILLER, S. S., 1981. Intravenous radionclide cystography for the detection of vesico-renal reflux. Journal of Urology, 125, 75-78. RANSLEY, P. G. & RISDON, R. A., 1975. Papillary morphology
in infants 111-113.
and young children.
Urology Research, 3,
ROTHWELL, D. L., CONSTABLE, A. R., & ALBRECHT, M., 1977.
KRAMER-
Radionuclide cystography in the investigation of vesicoureteric reflux in children. Lancet, i, 1072-1075.
of pyelonephritis.
SAXENA, S. R., LAWRENCE, B. M. & SHAW, D. G., 1975. The
CONWAY, J. J. & KRUGLIK, G. D., 1976. Effectiveness of direct
justification for early radiological investigation of urinary tract in children. Lancet, ii, 403.
CHRISTOPHE,
C,
BOGAERT,
C,
SPEHL,
PERMULTER, N., 1983. Ultrasound Pediatrics, 13, 173.
M.
&
and indirect radionuclide cystography in detecting vesicoureteral reflux. Journal of Nuclear Medicine, 17, 81-83. DIAMENT, M. J., 1988. Is ultrasound screening for urinary tract infection cost effective? Pediatric Radiology, 18, 157-159. DICKSON, J. A., 1979. Incidence and outcome of symptomatic urinary tract infection in children. British Medical Journal, i, 1330-1332.
SHERWOOD, T. & WHITAKER, R. H., 1984. Initial screening of
children with urinary tract radiography and ultrasound Journal, 288, 827.
infections: is plain film enough? British Medical
SMELLIE, J. M., EDWARDS, D., HUNTER, N., NORMAND, I. C. S.
& PRESCOD, N., 1975. Vesico-ureteric reflux and renal scarring. Kidney International, 8, s65-s72.
FILLY, R. A., FRIEDLAND, G. W., GOVEN, D. E. & FAIR, W. R.,
SMELLIE, J. M., RANSLEY, P. G., NORMAND, I. C. S., PRESCOD,
1974. Development and progression of clubbing and scarring in children with recurrent urinary tract infection. Radiology, 113, 145-153.
N. & EDWARDS, D., 1985. Development of new renal scars: a collaborative study. British Medical Journal, 290, 1957-1960.
GOLDRAICH, N. P., RAMOS, O. L. & GOLDRAICH, I. H., 1989.
Urography versus DMSA scan in children with vesicoureteric reflux. Pediatric Nephrology, 3, 1-5. HAYCOCK, G. B., 1986. Investigation of urinary tract infection. Archives of Disease in Childhood, 12, 1155-1158. HANDMAKER, H., MCRAE, J. & BUCK, E. G., 1973. Intravenous
radionuclide voiding cystography (IRVC). Radiology, 108, 703-705. HODSON, C. J. & WILSON, S., 1965. Natural history of chronic pyelonephritic scarring. British Medical Journal, 2, 191-194. HUGOSSON, C. O., CHRISPIN, A. R. & WOLVERSON, M. K., 1976.
The advent of the pyelonephrotic scar. Annals of Radiology, 19, 1-6. JAQUIER, S., BORGES, M., FORBES, P. & NOGRADY, M. B., 1983.
The value of ultrasound examination as a screening procedure in first documented urinary tract infection in children. Pediatric Radiology, 13, 173. KANGARLOO, H., GOLD, R. H., FINE, R. N. & DIAMENT, M. J.,
1985. Urinary tract infection in infants and children evaluated by ultrasound. Radiology, 155, 367-374. KENNEY, I., 1989. Personal communication. MAJD, M., 1986. Comparison of direct and indirect isotope cystography. Radiology, 158, 228. MERRICK, M., UTTLEY, W. S. & WILD, S. R.,
1980. The
detection of pyelonephritic scarring in children by isotope imaging. British Journal of Radiology, 53, 544-556. MONSOUR, M., AZMY, A. F. & MACKENZIE, J. R., 1987. Renal
scarring secondary to VUR. Critical assessment and new grading. British Journal of Urology, 60, 320-324.
Vol. 63, No. 751
SMELLIE, J. M., SHAW, P. J., PRESCOD, N. P. & BANTOCK, H.
M., 1988. 99m Tc DMSA scan in patients with established radiological scarring. Archives of Disease in Childhood, 63, 1315-1319. SMYTH, R. L., BERMAN, L. & VALMAN, H. B., 1988. Current
practice in managing urinary tract infection in children. British Medical Journal, 297, 1516-1517. STROLLER,
M.
L. & KOGAN,
B. A.,
1986. Sensitivity
of
Tc 99m DMSA for the diagnosis of chronic pyelonephritis: Clinical and theoretical considerations. Journal of Urology, 135, 977-980. VAN DER VlS-MELSEN, M. J. E., BAERT, R. J. M., RAJNHERC, J. R. et al, 1989. Scintigraphic assessment of lower urinary tract function in children with and without outflow tract obstruction. British Journal of Urology, 64, 263-269. VERBER, I. G., STRUDLEY, M. R. & MELLER, S. T., 1988.
99m Tc DMSA scan as first investigation of urinary tract infection. Archives of Disease in Childhood, 63, 1302-1325. WHITE, R. H. R., 1989. Vesicoureteric reflux and renal scarring. Archives of Disease in Childhood, 64, 407-412. WHYTE, K. M., ABBOT, G. D., KENNEDY, J. C. & MALING, T.
M. J., 1988. A protocol for the investigation of infants and children with urinary tract infection. Clinical Radiology, 39, 278-280. WILLIAMS, C. M., 1976. Urinary tract infection in children: general practice survey. Aust. Fam. Physician, 5, 340-344. WILLI, U. V. & TREVES, S. T., 1985. Radionuclide voiding
cystography. In Paediatric Nuclear Medicine, ed. by S. T. Treves, (Springer-Verlag, New York), p. 105.
511
