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Dysfunctional elimination syndrome is a negative predictor for vesicoureteral reflux
Journal of Pediatric Urology (2006) 2, 312e315
Dysfunctional elimination syndrome is a negative predictor for vesicoureteral reflux John Colen, Steven G. Docimo, Kate Stanitski, Danielle D. Sweeney, Barbara Wise, Patricia Brandt, Hsi-Yang Wu* Department of Pediatric Urology, Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA Received 11 October 2005; accepted 6 January 2006 Available online 31 March 2006
KEYWORDS Vesicoureteral reflux; Urinary tract infection; Voiding cystourethrogram
Abstract Purpose: We investigated the likelihood of finding vesicoureteral reflux (VUR) in patients with urinary tract infections (UTIs), accompanied by fever or dysfunctional elimination syndrome (DES). Materials and methods: Two hundred consecutive voiding cystourethrograms performed in 1997e2002 for a diagnosis of UTI were reviewed. Fever, DES, and the grade and laterality of VUR were recorded. Patients were stratified into two groups by age to allow for assessment of DES symptoms in the older patient population: <2 years (n ¼ 68) and 2 years (n ¼ 132). Ratios were compared using a two-tailed Fisher’s exact test. Results: Of the children 2 years old, 64/132 (48%) had VUR. Patients who were non-febrile with DES were less likely than patients who were febrile without DES to have VUR [12/34 (35%) vs 23/34 (68%), P ¼ 0.02], whereas the risk of dilating VUR [5/34 (15%) vs 11/34 (32%), P ¼ 0.15] and bilateral VUR [4/34 (12%) vs 11/34 (32%), P ¼ 0.08] was not statistically different. In febrile patients, the presence of DES was associated with a lower risk of VUR [22/51 (43%) vs 23/34 (68%), P ¼ 0.03] and dilating VUR [5/51 (10%) vs 11/34 (32%), P ¼ 0.01], but not bilateral VUR [8/51 (16%) vs 11/34 (32%), P ¼ 0.11]. Conclusions: Children with non-febrile UTI and DES have a significantly lower risk of having VUR compared to children with febrile UTI and no DES. Among children with a history of UTI, DES is a negative predictor for VUR. ª 2006 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
Introduction * Corresponding author. Department of Pediatric Urology, G205 DeSoto Wing, Children’s Hospital of Pittsburgh, 3705 5th Avenue, Pittsburgh, PA 15213, USA. Tel.: þ1 412 692 7932; fax: þ1 412 692 7939. E-mail address: [email protected] (H.-Y. Wu).
When Koff et al. [1] introduced the term ‘‘dysfunctional elimination syndrome’’ (DES) in 1998, they suggested that ‘‘primary [vesicoureteral] reflux
1477-5131/$30 ª 2006 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jpurol.2006.01.013
Effect of fever and DES on VUR should remain a diagnosis of exclusion and children with dysfunctional elimination syndrome should not be considered to have primary reflux’’. The concept that reflux is often secondary to DES was introduced. We sought to determine whether DES is an independent predictor for VUR, and if the presence of fever distinguishes those children with VUR in a group of children presenting with UTI. Our usual practice in a child with DES is to perform a VCUG only if the UTI is accompanied by fever, or if a renal ultrasound is abnormal. Because the majority of VCUGs at our institution are ordered by primary care physicians, who are less likely to discriminate between febrile and non-febrile UTI, we retrospectively analyzed the outcomes of all VCUGs performed for UTI at our hospital to determine the relationships between DES, febrile UTI, and the presence and severity of VUR.
Materials and methods This study was approved by the IRB of the Children’s Hospital of Pittsburgh. A list of all patients undergoing VCUG from 1997 to 2002 was obtained from the radiology department. The medical record was reviewed for evidence of UTI, and those patients without documented infection were excluded. Patients who were found to have other reasons for UTI or VUR such as kidney stones, hydronephrosis, PUV, ureterocele, or neuropathic bladder were also excluded. Two hundred patients were included in this study. The age at the time of VCUG rather than the age of first UTI was used, since some patients presented with a history of UTI which had not been previously studied. UTI was defined as symptoms of dysuria, nausea, vomiting, or fever accompanied by a positive urinalysis (10 or more white cells per mm3 in uncentrifuged urine and/or bacteriuria, one or more gram-negative rods per 10 oil-immersion fields in a Gram-stained smear of uncentrifuged urine) and/or a positive urine culture with >105 of a single organism. Fever was defined as temperature 38 C on initial presentation. The diagnosis of DES was based on one or more of the following: daytime urinary incontinence, posturing, urgency, constipation, encopresis, or previous documentation of the diagnosis. DES was not diagnosed in children < 2 years, or who were not yet potty trained, due to the difficulty of diagnosing DES in such a situation. VUR Grades I and II were considered non-dilating, and Grades IIIeV dilating. Rates were compared using a two-tailed Fisher’s exact test.
313
Results The results for children 2 years are listed in Table 1. Overall, 64/132 patients (48%) had VUR. Of the 132 patients, 122 were girls (92%), and 10 were boys (8%). The mean age was 70.2 months (5.9 years; range 24e205 months). There were 112 white and eight black children, with 18 unknown. Patients who were non-febrile with DES were less likely than those who were febrile without DES to have VUR (35% vs 68%, P ¼ 0.02). Among the febrile patients, those with DES were less likely than those without DES to have VUR (43% vs 68%, P ¼ 0.01) or dilating VUR (10% vs 32%, P ¼ 0.01). Abnormal renal ultrasounds were found in only 12 patients: two each in the non-febrile/ DES (), non-febrile/DES (þ), febrile/DES() groups, all of whom had VUR. Six patients in the febrile/DES(þ) group had abnormal ultrasounds, but only three had VUR. The results for children < 2 years are listed in Table 2. Of the 68 patients, 60 were girls (88%), and eight were boys (12%). The mean age was 8.6 months (range 1e23 months). Fifty-three were white and five were black, with 10 unknown. There were too few patients in the non-febrile group for statistical comparison with the febrile group. Fourteen patients had abnormal renal ultrasounds, of which eight had VUR.
Discussion If DES causes secondary reflux, then patients with DES should have higher rates of VUR than patients without DES. Our data suggest that DES is not a cause of secondary reflux, since patients with
Table 1
Results for children 2 years VUR
Non-febrile, 7/13 DES () Non-febrile, 12/34 DES (þ) Febrile, DES () 23/34 Febrile, DES (þ) 22/51
Dilating VUR
Bilateral VUR
(54)
3/13 (23)
5/13 (38)
(35)
5/34 (15)
4/34 (12)
(68) 11/34 (32) 11/34 (32) (43) 5/51 (10) 8/51 (16)
n ¼ 132, values in brackets are %. Comparison of non-febrile, DES (þ) with febrile, DES (): VUR, P ¼ 0.02; dilating VUR, P ¼ 0.15; bilateral VUR, P ¼ 0.08. Comparison of febrile, DES (þ) with DES (): VUR, P ¼ 0.03; dilating VUR, P ¼ 0.01; bilateral VUR, P ¼ 0.11. Comparison of non-febrile with febrile: VUR, P ¼ 0.2; dilating VUR, P ¼ 1.0; bilateral VUR, P ¼ 0.8.
314 Table 2
J. Colen et al. Results for children < 2 years
Non-febrile Febrile Overall
VUR
Dilating VUR
Bilateral VUR
3/4 47/64 (73) 50/68 (74)
3/4 29/64 (45) 32/68 (47)
2/4 26/64 (41) 28/68 (41)
n ¼ 68, values in brackets are %.
DES actually have a lower rate of VUR than those patients without DES. The initial paper by Koff et al. [1] describing the association between DES and reflux was not able to evaluate this because the entire population studied had VUR. We previously reported that in patients who presented with a febrile UTI < 2 years of age, the rate of DES diagnosed at age 7 years using the Dysfunctional Voiding Scoring System [2] was 22%, similar to the 21% of age-matched patients who presented with fever not due to UTI. The rates of subsequent DES in patients with and without VUR at presentation were also similar, being 18% and 25%, respectively. These results suggested that while the symptoms of DES are common in children, they are not brought on by early UTI, nor are children with VUR diagnosed in early childhood more likely to exhibit DES symptoms at school age [3]. We did not use the Dysfunctional Voiding Scoring System in this study because it was a retrospective chart review. A multivariate analysis of DES and VUR carried out on 2759 patients from St. Louis found that DES was more commonly found in patients with UTI but without VUR than in patients with UTI and VUR. It also showed that DES was not associated with an increased risk of UTI when VUR was not present [4]. The hypothesis that would best explain these data is that VUR and DES are common conditions which can influence each other without causing each other. Our data provide additional confirmation that DES complicates the management of VUR, by increasing the risk of UTI in patients with pre-existing VUR, rather than being the cause of it. We could not show that fever was useful in picking out the child who was more likely to have VUR, since approximately 40e50% had VUR with or without fever. Since the presence of fever is usually clinically interpreted as pyelonephritis rather than cystitis, and in larger studies is significantly linked with an increased likelihood of finding VUR [5], this may reflect either a small sample size or selection bias. Since the older patients whom we felt were less likely to have VUR generally did not have a VCUG performed, the percentage of patients with non-febrile UTI who had VUR is higher than if all patients were included.
The likelihood of VUR detection in this study is higher than in other series. Historically, approximately 50% of infants and 33% of older children who present with UTI are found to have VUR [6,7]. We found that almost 75% of infants and 50% of older children with UTI had VUR. We believe that this is most likely due to selection bias. In our hospital, the urology department orders more than a third of the VCUGs, with the remainder being ordered by primary care physicians. In addition, some of these patients had prior VCUGs performed at other hospitals. We presume that most patients who had VUR were referred to urology for management, and those with normal studies were not, thus enriching the VUR population. This should increase the likelihood of finding VUR in those children with DES, and should not affect the conclusions of this study. As we develop better selection criteria to determine which patient with UTI requires a VCUG, evidence showing that presumed risk factors such as age, fever, and presence of DES significantly affect the likelihood of finding VUR will hopefully allow both urologists and primary care physicians to utilize the VCUG more selectively. Renal ultrasound was not a useful screening tool for VUR in the older patient with non-febrile UTI and DES. We have traditionally only performed VCUG on such patients if there was a significant size discrepancy between the kidneys, suggesting that one kidney had been injured from previous infection. Abnormal renal ultrasounds were only found in 9% of the patients 2 years, and the two patients with non-febrile UTI, DES (þ), with abnormal renal ultrasounds and reflux had low-grade VUR. This is not surprising, since a review of the literature on the ability of renal ultrasound to detect renal scarring using DMSA scan as the gold standard found that the sensitivity varied from 37% to 100% [8]. While evidence of gross renal injury on ultrasound remains a reason to obtain a VCUG, finding normal-sized kidneys does not rule out renal injury. We found that 35% of patients in the presumed ‘low-risk’ group (non-febrile infections and DES) have VUR, and 15% have dilating reflux. Does this suggest our policy of reserving VCUG for patients with febrile infections or renal abnormalities is missing significant VUR? Unfortunately, the patients did not all have DMSA scans performed to look for renal scarring, so that question cannot be definitively answered. The suggestion that patients older than 1 year who present with UTI undergo DMSA rather than VCUG as the initial radiologic evaluation continues to be debated [9e12]. The argument is that the VUR discovered in the absence of renal injury in an older patient
Effect of fever and DES on VUR (up to 23% in one series) [13] is clinically insignificant. The question is whether one would manage a patient with a febrile UTI, Grade III VUR, and normal kidneys on DMSA scan without antibiotic prophylaxis [14,15]. Many of us are not yet comfortable with that approach, especially in younger children. Having the initial infection at age > 4 years with normal initial DMSA appears to minimize the risk of subsequent scarring even with continued infections [16]. The combination of an older patient and non-febrile infections increases our comfort level in managing them without a VCUG. A normal DMSA might be reassuring, but is probably not necessary with a normal ultrasound in children over 4 years of age. Although this study suggests that DES does not cause most VUR, it by no means diminishes the impact of DES on pre-existing VUR and the tendency toward recurrent or breakthrough UTI. DES was associated with a much higher rate of breakthrough infection in both the original description of DES [1] and in subsequent studies [4]. The impact of DES on VUR may be greater in decreasing host resistance by preventing frequent and complete emptying of the bladder and increasing the risk of UTI, rather than weakening the ureterovesical junction by raising voiding pressures. Patients who are referred to our department for UTI are routinely studied for abnormal bowel and bladder emptying and placed on appropriate regimens if abnormalities are found. One could argue that it is the patient who continues to have UTI despite proper management who should have a VCUG to look for a pre-existing anatomical condition that was worsened by a functional problem. In terms of how this affects treatment, it is reasonable to consider patients with VUR and DES as having primary reflux, so long as it is appreciated that the treatment of DES will positively impact resolution of VUR and decrease the risk of UTI, and patients are aware that VUR may persist even after successful correction of DES.
Conclusion Children with non-febrile UTI and DES have a significantly lower likelihood of having VUR compared to children with febrile UTI and no DES. Among children with a history of UTI, DES appears to be a negative predictor for VUR.
315
References [1] Koff SA, Wagner TT, Jayanthi VR. The relationship among dysfunctional elimination syndromes, primary vesicoureteral reflux and urinary tract infections in children. J Urol 1998;160:1019. [2] Farhat W, Bagli DJ, Capolicchio G, O’Reilly S, Merguerian PA, Khoury A, et al. The dysfunctional voiding scoring system: quantitative standardization of dysfunctional voiding symptoms in children. J Urol 2000;164: 1011. [3] Shaikh N, Hoberman A, Wise B, Kurs-Lasky M, Kearney D, Naylor S, et al. Dysfunctional elimination syndrome: is it related to urinary tract infection or vesicoureteral reflux diagnosed early in life? Pediatrics 2003;112:1134. [4] Chen JJ, Mao W, Homayoon K, Steinhardt G. A multivariate analysis of dysfunctional elimination syndrome, and its relationships with gender, urinary tract infection and vesicoureteral reflux in children. J Urol 2004;171: 1907. [5] Smellie JM, Normand ICS, Katz G. Children with urinary tract infection: a comparison of those with and those without vesicoureteric reflux. Kidney Int 1981;20:717. [6] American Academy of Pediatrics, Committee on Quality Improvement, Subcommittee on Urinary Tract Infection: Practice parameter: the diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. Pediatrics 1999;103:843. [7] Downs SM. Technical report: urinary tract infections in febrile infants and young children. Pediatrics 1999;103: e54. [8] Roebuck DJ, Howard RG, Metreweli C. How sensitive is ultrasound in the detection of renal scars? Br J Radiol 1999; 72:345. [9] Koff SA. A practical approach to evaluating urinary tract infection in children. Pediatr Nephrol 1991;5:398. [10] Haycock GB. A practical approach to evaluating urinary tract infection in children. Pediatr Nephrol 1991;5:401. [11] Gleeson FV, Gordon I. Imaging for urinary tract infection. Arch Dis Child 1991;66:1283. [12] Jakobsson B, Soderlundh S, Berg U. Diagnostic significance of 99mTc-dimercaptosuccinic (DMSA) scintigraphy in urinary tract infection. Arch Dis Child 1992;67:1338. [13] Kass EJ, Kernen KM, Carey JM. Paediatric urinary tract infection and the necessity of complete urological imaging. BJU Int 2000;86:94. [14] Hansson S, Dhamey M, Sigstrom O, Sixt R, Stockland E, Wennerstrom M, et al. Dimercapto-succinic acid scintigraphy instead of voiding cystourethrography for infants with urinary tract infection. J Urol 2004;172:1071. [15] Szlyk GR, Williams SB, Majd M, Belman AB, Rushton HG. Incidence of new renal parenchymal inflammatory changes following breakthrough urinary tract infection in patients with vesicoureteral reflux treated with antibiotic prophylaxis: evaluation by 99mtechnetium dimercapto-succinic acid renal scan. J Urol 2003;170:1566. [16] Vernon SJ, Coulthard MG, Lambert HJ, Keir MJ, Matthews JN. New renal scarring in children who at age 3 and 4 years had had normal scans with dimercaptosuccinic acid: follow up study. BMJ 1997;315:905.
Dysfunctional elimination syndrome is a negative predictor for vesicoureteral reflux John Colen, Steven G. Docimo, Kate Stanitski, Danielle D. Sweeney, Barbara Wise, Patricia Brandt, Hsi-Yang Wu* Department of Pediatric Urology, Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA Received 11 October 2005; accepted 6 January 2006 Available online 31 March 2006
KEYWORDS Vesicoureteral reflux; Urinary tract infection; Voiding cystourethrogram
Abstract Purpose: We investigated the likelihood of finding vesicoureteral reflux (VUR) in patients with urinary tract infections (UTIs), accompanied by fever or dysfunctional elimination syndrome (DES). Materials and methods: Two hundred consecutive voiding cystourethrograms performed in 1997e2002 for a diagnosis of UTI were reviewed. Fever, DES, and the grade and laterality of VUR were recorded. Patients were stratified into two groups by age to allow for assessment of DES symptoms in the older patient population: <2 years (n ¼ 68) and 2 years (n ¼ 132). Ratios were compared using a two-tailed Fisher’s exact test. Results: Of the children 2 years old, 64/132 (48%) had VUR. Patients who were non-febrile with DES were less likely than patients who were febrile without DES to have VUR [12/34 (35%) vs 23/34 (68%), P ¼ 0.02], whereas the risk of dilating VUR [5/34 (15%) vs 11/34 (32%), P ¼ 0.15] and bilateral VUR [4/34 (12%) vs 11/34 (32%), P ¼ 0.08] was not statistically different. In febrile patients, the presence of DES was associated with a lower risk of VUR [22/51 (43%) vs 23/34 (68%), P ¼ 0.03] and dilating VUR [5/51 (10%) vs 11/34 (32%), P ¼ 0.01], but not bilateral VUR [8/51 (16%) vs 11/34 (32%), P ¼ 0.11]. Conclusions: Children with non-febrile UTI and DES have a significantly lower risk of having VUR compared to children with febrile UTI and no DES. Among children with a history of UTI, DES is a negative predictor for VUR. ª 2006 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
Introduction * Corresponding author. Department of Pediatric Urology, G205 DeSoto Wing, Children’s Hospital of Pittsburgh, 3705 5th Avenue, Pittsburgh, PA 15213, USA. Tel.: þ1 412 692 7932; fax: þ1 412 692 7939. E-mail address: [email protected] (H.-Y. Wu).
When Koff et al. [1] introduced the term ‘‘dysfunctional elimination syndrome’’ (DES) in 1998, they suggested that ‘‘primary [vesicoureteral] reflux
1477-5131/$30 ª 2006 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jpurol.2006.01.013
Effect of fever and DES on VUR should remain a diagnosis of exclusion and children with dysfunctional elimination syndrome should not be considered to have primary reflux’’. The concept that reflux is often secondary to DES was introduced. We sought to determine whether DES is an independent predictor for VUR, and if the presence of fever distinguishes those children with VUR in a group of children presenting with UTI. Our usual practice in a child with DES is to perform a VCUG only if the UTI is accompanied by fever, or if a renal ultrasound is abnormal. Because the majority of VCUGs at our institution are ordered by primary care physicians, who are less likely to discriminate between febrile and non-febrile UTI, we retrospectively analyzed the outcomes of all VCUGs performed for UTI at our hospital to determine the relationships between DES, febrile UTI, and the presence and severity of VUR.
Materials and methods This study was approved by the IRB of the Children’s Hospital of Pittsburgh. A list of all patients undergoing VCUG from 1997 to 2002 was obtained from the radiology department. The medical record was reviewed for evidence of UTI, and those patients without documented infection were excluded. Patients who were found to have other reasons for UTI or VUR such as kidney stones, hydronephrosis, PUV, ureterocele, or neuropathic bladder were also excluded. Two hundred patients were included in this study. The age at the time of VCUG rather than the age of first UTI was used, since some patients presented with a history of UTI which had not been previously studied. UTI was defined as symptoms of dysuria, nausea, vomiting, or fever accompanied by a positive urinalysis (10 or more white cells per mm3 in uncentrifuged urine and/or bacteriuria, one or more gram-negative rods per 10 oil-immersion fields in a Gram-stained smear of uncentrifuged urine) and/or a positive urine culture with >105 of a single organism. Fever was defined as temperature 38 C on initial presentation. The diagnosis of DES was based on one or more of the following: daytime urinary incontinence, posturing, urgency, constipation, encopresis, or previous documentation of the diagnosis. DES was not diagnosed in children < 2 years, or who were not yet potty trained, due to the difficulty of diagnosing DES in such a situation. VUR Grades I and II were considered non-dilating, and Grades IIIeV dilating. Rates were compared using a two-tailed Fisher’s exact test.
313
Results The results for children 2 years are listed in Table 1. Overall, 64/132 patients (48%) had VUR. Of the 132 patients, 122 were girls (92%), and 10 were boys (8%). The mean age was 70.2 months (5.9 years; range 24e205 months). There were 112 white and eight black children, with 18 unknown. Patients who were non-febrile with DES were less likely than those who were febrile without DES to have VUR (35% vs 68%, P ¼ 0.02). Among the febrile patients, those with DES were less likely than those without DES to have VUR (43% vs 68%, P ¼ 0.01) or dilating VUR (10% vs 32%, P ¼ 0.01). Abnormal renal ultrasounds were found in only 12 patients: two each in the non-febrile/ DES (), non-febrile/DES (þ), febrile/DES() groups, all of whom had VUR. Six patients in the febrile/DES(þ) group had abnormal ultrasounds, but only three had VUR. The results for children < 2 years are listed in Table 2. Of the 68 patients, 60 were girls (88%), and eight were boys (12%). The mean age was 8.6 months (range 1e23 months). Fifty-three were white and five were black, with 10 unknown. There were too few patients in the non-febrile group for statistical comparison with the febrile group. Fourteen patients had abnormal renal ultrasounds, of which eight had VUR.
Discussion If DES causes secondary reflux, then patients with DES should have higher rates of VUR than patients without DES. Our data suggest that DES is not a cause of secondary reflux, since patients with
Table 1
Results for children 2 years VUR
Non-febrile, 7/13 DES () Non-febrile, 12/34 DES (þ) Febrile, DES () 23/34 Febrile, DES (þ) 22/51
Dilating VUR
Bilateral VUR
(54)
3/13 (23)
5/13 (38)
(35)
5/34 (15)
4/34 (12)
(68) 11/34 (32) 11/34 (32) (43) 5/51 (10) 8/51 (16)
n ¼ 132, values in brackets are %. Comparison of non-febrile, DES (þ) with febrile, DES (): VUR, P ¼ 0.02; dilating VUR, P ¼ 0.15; bilateral VUR, P ¼ 0.08. Comparison of febrile, DES (þ) with DES (): VUR, P ¼ 0.03; dilating VUR, P ¼ 0.01; bilateral VUR, P ¼ 0.11. Comparison of non-febrile with febrile: VUR, P ¼ 0.2; dilating VUR, P ¼ 1.0; bilateral VUR, P ¼ 0.8.
314 Table 2
J. Colen et al. Results for children < 2 years
Non-febrile Febrile Overall
VUR
Dilating VUR
Bilateral VUR
3/4 47/64 (73) 50/68 (74)
3/4 29/64 (45) 32/68 (47)
2/4 26/64 (41) 28/68 (41)
n ¼ 68, values in brackets are %.
DES actually have a lower rate of VUR than those patients without DES. The initial paper by Koff et al. [1] describing the association between DES and reflux was not able to evaluate this because the entire population studied had VUR. We previously reported that in patients who presented with a febrile UTI < 2 years of age, the rate of DES diagnosed at age 7 years using the Dysfunctional Voiding Scoring System [2] was 22%, similar to the 21% of age-matched patients who presented with fever not due to UTI. The rates of subsequent DES in patients with and without VUR at presentation were also similar, being 18% and 25%, respectively. These results suggested that while the symptoms of DES are common in children, they are not brought on by early UTI, nor are children with VUR diagnosed in early childhood more likely to exhibit DES symptoms at school age [3]. We did not use the Dysfunctional Voiding Scoring System in this study because it was a retrospective chart review. A multivariate analysis of DES and VUR carried out on 2759 patients from St. Louis found that DES was more commonly found in patients with UTI but without VUR than in patients with UTI and VUR. It also showed that DES was not associated with an increased risk of UTI when VUR was not present [4]. The hypothesis that would best explain these data is that VUR and DES are common conditions which can influence each other without causing each other. Our data provide additional confirmation that DES complicates the management of VUR, by increasing the risk of UTI in patients with pre-existing VUR, rather than being the cause of it. We could not show that fever was useful in picking out the child who was more likely to have VUR, since approximately 40e50% had VUR with or without fever. Since the presence of fever is usually clinically interpreted as pyelonephritis rather than cystitis, and in larger studies is significantly linked with an increased likelihood of finding VUR [5], this may reflect either a small sample size or selection bias. Since the older patients whom we felt were less likely to have VUR generally did not have a VCUG performed, the percentage of patients with non-febrile UTI who had VUR is higher than if all patients were included.
The likelihood of VUR detection in this study is higher than in other series. Historically, approximately 50% of infants and 33% of older children who present with UTI are found to have VUR [6,7]. We found that almost 75% of infants and 50% of older children with UTI had VUR. We believe that this is most likely due to selection bias. In our hospital, the urology department orders more than a third of the VCUGs, with the remainder being ordered by primary care physicians. In addition, some of these patients had prior VCUGs performed at other hospitals. We presume that most patients who had VUR were referred to urology for management, and those with normal studies were not, thus enriching the VUR population. This should increase the likelihood of finding VUR in those children with DES, and should not affect the conclusions of this study. As we develop better selection criteria to determine which patient with UTI requires a VCUG, evidence showing that presumed risk factors such as age, fever, and presence of DES significantly affect the likelihood of finding VUR will hopefully allow both urologists and primary care physicians to utilize the VCUG more selectively. Renal ultrasound was not a useful screening tool for VUR in the older patient with non-febrile UTI and DES. We have traditionally only performed VCUG on such patients if there was a significant size discrepancy between the kidneys, suggesting that one kidney had been injured from previous infection. Abnormal renal ultrasounds were only found in 9% of the patients 2 years, and the two patients with non-febrile UTI, DES (þ), with abnormal renal ultrasounds and reflux had low-grade VUR. This is not surprising, since a review of the literature on the ability of renal ultrasound to detect renal scarring using DMSA scan as the gold standard found that the sensitivity varied from 37% to 100% [8]. While evidence of gross renal injury on ultrasound remains a reason to obtain a VCUG, finding normal-sized kidneys does not rule out renal injury. We found that 35% of patients in the presumed ‘low-risk’ group (non-febrile infections and DES) have VUR, and 15% have dilating reflux. Does this suggest our policy of reserving VCUG for patients with febrile infections or renal abnormalities is missing significant VUR? Unfortunately, the patients did not all have DMSA scans performed to look for renal scarring, so that question cannot be definitively answered. The suggestion that patients older than 1 year who present with UTI undergo DMSA rather than VCUG as the initial radiologic evaluation continues to be debated [9e12]. The argument is that the VUR discovered in the absence of renal injury in an older patient
Effect of fever and DES on VUR (up to 23% in one series) [13] is clinically insignificant. The question is whether one would manage a patient with a febrile UTI, Grade III VUR, and normal kidneys on DMSA scan without antibiotic prophylaxis [14,15]. Many of us are not yet comfortable with that approach, especially in younger children. Having the initial infection at age > 4 years with normal initial DMSA appears to minimize the risk of subsequent scarring even with continued infections [16]. The combination of an older patient and non-febrile infections increases our comfort level in managing them without a VCUG. A normal DMSA might be reassuring, but is probably not necessary with a normal ultrasound in children over 4 years of age. Although this study suggests that DES does not cause most VUR, it by no means diminishes the impact of DES on pre-existing VUR and the tendency toward recurrent or breakthrough UTI. DES was associated with a much higher rate of breakthrough infection in both the original description of DES [1] and in subsequent studies [4]. The impact of DES on VUR may be greater in decreasing host resistance by preventing frequent and complete emptying of the bladder and increasing the risk of UTI, rather than weakening the ureterovesical junction by raising voiding pressures. Patients who are referred to our department for UTI are routinely studied for abnormal bowel and bladder emptying and placed on appropriate regimens if abnormalities are found. One could argue that it is the patient who continues to have UTI despite proper management who should have a VCUG to look for a pre-existing anatomical condition that was worsened by a functional problem. In terms of how this affects treatment, it is reasonable to consider patients with VUR and DES as having primary reflux, so long as it is appreciated that the treatment of DES will positively impact resolution of VUR and decrease the risk of UTI, and patients are aware that VUR may persist even after successful correction of DES.
Conclusion Children with non-febrile UTI and DES have a significantly lower likelihood of having VUR compared to children with febrile UTI and no DES. Among children with a history of UTI, DES appears to be a negative predictor for VUR.
315
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