Abstract The prevalence of vesicoureteric reflux(VUR) in children with urinary tract infection (UTI) var-ies among different racial groups. The purpose of thisstudy was to determine the frequency of VUR and asso-ciated renal changes in a group of Arab Kuwaiti childrenwith their first documented febrile UTI and to compareour findings with those reported from other racialgroups. One hundred and seventy-four children (38males and 136 females) fulfilled the study criteria andwere divided into three age groups (<1 year, 1–5 years,and >5 years). Patients in each group had both micturat-ing cystourethrography (MCUG) and 99m-Tc-dimercap-tosuccinic acid (DMSA) renal scan after diagnosis. VURwas detected in 39 children (22%). Two-thirds of caseshad mild reflux (grade I and II). Females (n=32) hadmore reflux than males (n=7) (24% vs. 18%). Sixty-threepatients (36%) had abnormal (DMSA) renal scans (acutepyelonephritis [AP] or renal scars). Of these, 79% werechildren below 5 years. Abnormal DMSA scans werefound in 4 of 38 males (11%) versus 59 of 136 females(43%). Abnormal scans in children with VUR were seenin 1 of 7 males (14%) versus 19 of 32 females (59%). Intotal, the combination of abnormal scan with VUR oc-curred in 1 of 38 males (3%) and in 19 of 136 females(14%), whereas abnormal scan without demonstrableVUR was seen in 3 of 38 males (8%) versus 40 of 136females (29%). Our data showed that the frequency of

VUR in Arab Kuwaiti children with febrile UTI is mid-way between Caucasian and other racial groups. In thisstudy, males had a lower-risk profile than females, thelatter having a higher rate of reflux as well as a higherrate of abnormal DMSA scans, irrespective of demon-strable VUR.

Keywords Acute pyelonephritis · Renal scars · Arab children · Kuwait · Febrile urinary tract infection ·Vesicoureteric reflux

Introduction

Vesicoureteric reflux (VUR) is the most common anom-aly detected in children with urinary tract infection(UTI) [1]. The association of VUR with UTI increasesthe risk of acute pyelonephritis (AP), especially in youngchildren [1, 2]. Fever associated with UTI suggests renalinvolvement (AP), which places the kidneys at increasedrisk of renal scarring with its complications.

Various studies have supported the fact that the occur-rence of VUR, as detected by micturating cystourethrog-raphy (MCUG), varies among different racial groups andthat reflux will improve with age as the anti-refluxmechanisms mature [3, 4, 5].

The purpose of this study was to determine the fre-quency of VUR and associated kidney involvement (APand scar) among a group of Arab Kuwaiti children withtheir first documented febrile UTI. We believe this workis the first from this part of the world to be published inthe English literature.

Patients and methods

We performed a retrospective case review of all children consecu-tively admitted to two regional hospitals in Kuwait (Farwania andAl Adan) with the diagnosis of the first febrile UTI over a 6-yearperiod (June 1995 to June 2001). These two hospitals are the onlyreferral facilities for children with UTI in their respective catch-ment area. The study included children less than 12 years of age,

M. Zaki · G. A. MutariDepartment of Pediatrics, Farwania Hospital,Kuwait

M. Badawi · E. A. deen HanafyDepartment of Pediatrics, Al Adan Hospital,Kuwait

D. RamadanDepartment of Pediatrics, Sabah Hospital,Kuwait

M. Zaki (✉)P.O. Box 25850 Safat, Postal code 13119, Kuwaite-mail: redc66@yahoo.comTel.: +965-488-5251

Pediatr Nephrol (2003) 18:898–901DOI 10.1007/s00467-003-1219-9

O R I G I N A L A RT I C L E

Mohamed Zaki · Ghalia AL Mutari · Mona BadawiDina Ramadan · Emad Al deen Hanafy

Vesicoureteric reflux in Kuwaiti children with first febrile urinary tract infection

Received: 15 July 2002 / Revised: 24 April 2003 / Accepted: 1 May 2003 / Published online: 18 July 2003© IPNA 2003

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all of whom had undergone both MCUG to document the presenceof VUR and determine its grade, as well as 99m-Tc-dimercapto-succinic acid (DMSA) renal scan for detecting renal involvement(AP or scar).

All patients had three urine cultures positive for the same bac-terial pathogens. The urine samples were collected, depending onage of patients, by catheter, clean-catch or mid-urine stream. Allchildren in the study had temperatures >38.5 C at presentation. Inaddition, all had raised erythrocyte sedimentation rates(>40 mm/h) and C-reactive protein (>40 mg/l) as laboratory evi-dence suggestive of pyelonephritis. It is our policy to performDMSA scans within the 1st week of initiating treatment and toperform MCUG at least 1 month after diagnosis. Seven childrenwith febrile UTI were not included since their parents refused con-sent for MCUG because of its invasive nature. Two children withVUR secondary to neurogenic bladder associated with meningo-myelocele were also excluded from the study. Additionally, we ex-cluded 19 children (non-Kuwaiti Arabs and non-Arab children) inorder to have a homogenous racial group. All male patients hadbeen circumcised. It is the local custom here to circumcise malechildren after the 1st week of life.

DMSA renal scintigraphy was performed 2 h after injection of99m-Tc-DMSA taking one posterior, one anterior, and two poste-rior oblique images (250,000 counts) by gamma camera with thepatient in the prone position. The fractional left and right renal ac-tivity was calculated for each kidney after background correction.A kidney uptake of 45%–55% of the total renal activity was con-sidered normal. AP was defined as single or multiple areas of di-minished uptake of DMSA with preservation of the renal contour.Renal scar was defined as focal or generalized areas of diminisheduptake of the isotope associated with loss or contraction of func-tion renal cortex. This may appear as wedge-shaped defects, corti-cal thinning or flattening. All renal scans were reviewed by thesame panel of nuclear radiologists. Follow-up DMSA scans wereperformed for those with initial abnormal findings. The findingsof follow-up studies are not reported here.

MCUG was performed using urograffin 30%, which was in-stilled into the bladder through a pediatric feeding tube or Foley’scatheter according to patient’s age, by gravity until voiding oc-curred. Antero-posterior imaging of the bladder was performedduring early filling and when the bladder filling was complete.Oblique views centered on the ureterovesical junction were ob-tained. If reflux was observed, the episilateral renal fossa was im-aged before voiding. A post-void film of the bladder was taken todocument residual bladder volume. For male children, a view ofthe urethra was also obtained.

The children in the study were divided into three age groups(<1 year, 1–5 years, and >5 years). This division was based onprevious reports documenting an increased incidence of reflux inthe younger children with subsequent resolution with age, and thefact that AP and the development of new kidney scars are uncom-mon in children above the age of 5 years [5, 6]. The gradingsystem used was that of the International Reflux Study Group,with reflux graded from I to V [7].

Results

During the study period, a total of 174 children, 38 males(22%) and 136 females (78%), fulfilled the criteria for in-clusion in the study. Thirty-nine patients (22%) had VUR.The frequency of VUR detected in the three age groupswas 25%, 18%, and 27%, respectively. Two-thirds ofcases had mild reflux (grade I and II). Females (n=32) hadmore reflux than males (n=7) (24% vs. 18%). Sixty-threepatients (36%) had abnormal findings on DMSA scan (APin 43 cases and renal scars in 20 cases). Abnormal DMSAscans were found in 4 of 38 males (11%) versus 59 of 136females (43%). Abnormal scans in children with VURwere seen in 1 of 7 males (14%) versus 19 of 32 females(59%). Among the whole group of patients the combina-tion of abnormal scan with VUR occurred in 1 of 38males (3%) and in 19 of 136 females (14%), whereas ab-normal scan without demonstrable VUR was seen in 3 of38 males (8%) versus 40 of 136 females (29%). Table 1details the findings in the three age groups.

Group I (<1 year, 72 patients)

In this group, 47% were males (34/72). VUR was foundin 18 children (25%); 11 had unilateral reflux (8 gradeI–II and 3 grade III–IV). Seven had bilateral VUR, 14 re-fluxing ureters (9 grade I–II and 5 grade III–IV). An ab-normal DMSA scan was detected in 13 patients (18%).AP was present in 10, while 3 had renal scars. Five pa-tients (7%) had both VUR and abnormal DMSA scans atdiagnosis. Of the 3 children who had renal scars at pre-sentation, 1 was 7 months old with grade I reflux on theaffected side and the other 2, aged 3 and 9 months, hadno reflux. DMSA scan detected an absent kidney in amale patient and a horseshoe kidney in another. Escheri-chia coli was the most frequently isolated organism from55 children, followed by Klebsiella spp from 14, Proteusspp in 2, and enterococci in 1.

Group II (1–5 years, 66 patients)

There were only 3 males in this group. VUR was detect-ed in 12 patients (18%). Seven had unilateral reflux

Table 1 Findings of dimercaptosuccinic acid (DMSA) renal scan and micturating cystourethrography (MCUG) in 174 children withtheir first febrile urinary tract infection (N normal,VUR vesicoureteric reflux)

Age group I (<1 year) II (1–5 years) III (>5 years)Total number of patients 72 66 36

Sex M (n=34) F (n=38) M (n=3) F (n=63) M (n=1) F (n=35)

MCUG N VUR N VUR N VUR N VUR N VUR N VUR28 6 26 12 2 1 52 11 1 0 26 9

DMSA N 26 6 20 7 1 0 28 2 1 0 16 4Abnormal 2 0 6 5 1 1 24 9 0 0 10 5

(4 grade I–II and 3 grade III–IV). Five had bilateral re-flux, 10 refluxing ureters (8 grade I–II and 2 gradeIII–IV). Abnormal DMSA scan was detected in 35(53%) patients. Pyelonephritis changes were present in24 patients, of whom 5 had bilateral involvement. Elevenhad renal scars, including 4 with VUR on the affectedside. Of the 66 patients in this group, 9 (14%) had bothVUR and abnormal DMSA scan at presentation. E. coliwas isolated in 62 patients, while Klebsiella spp wereisolated in 2, and Proteus spp in a further 2.

Group III (36 patients >5 years)

There was only 1 male patient in this group. VUR wasdetected in 9 patients (25%). Unilateral reflux was pres-ent in 6 (4 grade I–II and 2 grade III–IV). Bilateral VURwas present in 3 patients, 6 refluxing ureters (2 grade I–IIand 4 grade III–IV). Fifteen children (41%) had abnormalDMSA scan (9 with AP and 6 with renal scars). Of thosewith renal scars, 2 patients had VUR. Five patients (13%)had both VUR and abnormal DMSA scans. E. coli wasthe most common isolated microorganism, while Kleb-siella spp and Proteus spp were each isolated only once.

Discussion

The incidence of VUR in the general population is notknown, but it is probably between 0.4% and 1.8% [8].The prevalence of VUR in children with UTI variesamong different racial groups, being highest in whitechildren with symptomatic UTI. Studies from the UnitedStates, United Kingdom, and Italy showed the highestprevalence of VUR (41%–63%) [3, 9, 10]. In other coun-tries with a predominately Caucasian population (Swe-den and Australia), the prevalence is lower (24%–27%)[11, 12]. Howard et al. [13] reported the presence ofVUR in 39% of symptomatic Chinese children with UTI.In our series of Arab children from Kuwait with first fe-brile UTI, VUR was present in 22% of patients. Thelowest reported prevalence of VUR in children with UTIwas in black American children (6%–12%) and in Jamai-can children (10%) [3, 4, 14]. Such variations may re-present delayed maturation of the anti-reflux mechanismin those children with the high prevalence rate, and thatgenetics may play a role. There is evidence that isolatedprimary VUR has a genetic basis, with an autosomaldominant pattern of inheritance, with incomplete pene-trance and variable expression [15, 16]. However, the in-heritance may be heterogeneous [15].

Of the 63 patients with abnormal DMSA scan at diag-nosis, only 20 (32%) had VUR, while in 43 patients(68%) VUR was not demonstrated. Uptake defects onDMSA scan suggestive of AP or scars in the absence ofVUR have been previously reported [6, 17, 18]. Our re-sults have also shown that normal DMSA scans canpresent in children with febrile UTI and VUR. Suchfindings support the view that VUR is not the only risk

factor involved in the causation of renal inflammationand that additional factors are also required. Bacterialvirulence, host reaction to infections, and bladder dys-function are among those factors responsible for pyelo-nephritis and subsequent scarring [6, 17]. AbnormalDMSA scans were more frequently seen in females thanin males, irrespective of VUR.

Among the 63 patients (35% of total study popula-tion) who had abnormal DMSA at diagnosis, 20 (32%)had renal scars at presentation. Such scars could havebeen acquired as a result of previously unrecognized in-fections or could represent congenital scars that are usu-ally associated with severe grades of reflux and representrenal dysplasia [17]. Differentiation between acquiredand congenital scars may not be possible on DMSAscan, especially in older children.

In our patients, although febrile UTI was more fre-quent below 1 year of age, renal scarring at presentationwas more common above that age. This was similar tofindings reported by others [18, 19, 20]. This could bedue to the duration required for a scar to develop or be-cause renal scars have developed as a result of previous-ly unrecognized UTIs that are often mistaken for otherfebrile illnesses.

In this study, female patients had a higher frequencyof reflux than males (24% vs. 18%). The predominanceof primary VUR in females with UTI has also been pre-viously reported [21]. E. coli was the most commonlyisolated microorganism from all age groups, as reportedby others [22].

In summary, this work has shown that occurrence ofVUR in Arab Kuwaiti children with febrile UTI is lessfrequent than in Caucasian children and is higher in chil-dren younger than 5 years. It also shows that males had alower risk profile than females, the latter having a higherrate of reflux as well as a higher rate of abnormal DMSAscans, irrespective of demonstrable VUR.

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