Controversy exists regarding the type and/or sequence of imaging studies needed during the first febrile urinary tract infection (UTI) in young children. Several investigators have claimed that because acute-phase Tc-99m dimercaptosuccinic acid (DMSA) renal-scan results are abnormal in the presence of dilating vesicoureteral reflux, a normal DMSA-scan result makes voiding cystourethrography (VCUG) unnecessary in the primary examination of infants with UTI. To evaluate the accuracy of acute-phase DMSA scanning in identifying dilating (grades III through V) vesicoureteral reflux documented by VCUG in children with a first febrile UTI, we performed a meta-analysis of the accuracy of diagnostic tests as reported from relevant studies identified through the PubMed and Scopus databases. Patient-based and renal unit–based analyses were performed. Overall, 13 cohort studies were identified. Nine studies involved patients younger than 2 years, 3 involved children aged 16 years or younger, and 1 involved exclusively neonates. Girls constituted 22% to 85% of the involved children. Pooled (95% confidence intervals) sensitivity and specificity rates of DMSA scanning were 79% and 53%, respectively, for the patient-based analysis (8 studies) and 60% and 65% for the renal unit–based analysis (5 studies). The respective areas under the hierarchical summary receiver operating curves were 0.71 and 0.67. Marked statistical heterogeneity was observed in both analyses, as indicated by I2 test values of 91% and 87%, respectively. Acute-phase DMSA renal scanning cannot be recommended as replacement for VCUG in the evaluation of young children with a first febrile UTI.
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July 2011
Review Articles|
July 01 2011
Acute Tc-99m DMSA Scan for Identifying Dilating Vesicoureteral Reflux in Children: A Meta-analysis Available to Purchase
Elpis Mantadakis, MD;
Elpis Mantadakis, MD
aDepartment of Pediatrics, Democritus University of Thrace and University General Hospital of Alexandroupolis, Thrace, Greece;
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Evridiki K. Vouloumanou, MD;
Evridiki K. Vouloumanou, MD
bAlfa Institute of Biomedical Sciences (AIBS), Athens, Greece;
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Georgia G. Georgantzi, MD;
Georgia G. Georgantzi, MD
bAlfa Institute of Biomedical Sciences (AIBS), Athens, Greece;
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Aggelos Tsalkidis, MD;
Aggelos Tsalkidis, MD
aDepartment of Pediatrics, Democritus University of Thrace and University General Hospital of Alexandroupolis, Thrace, Greece;
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Αthanassios Chatzimichael, MD;
Αthanassios Chatzimichael, MD
aDepartment of Pediatrics, Democritus University of Thrace and University General Hospital of Alexandroupolis, Thrace, Greece;
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Matthew E. Falagas, MD, MSc, DSc
bAlfa Institute of Biomedical Sciences (AIBS), Athens, Greece;
cDepartment of Medicine, Henry Dunant Hospital, Athens, Greece; and
dDepartment of Medicine, Tufts University School of Medicine, Boston, Massachusetts
Address correspondence to Matthew E. Falagas, MD, MSc, DSc, Alfa Institute of Biomedical Sciences (AIBS), 9 Neapoleos St, 151 23 Marousi, Athens, Greece. E-mail: [email protected]
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Address correspondence to Matthew E. Falagas, MD, MSc, DSc, Alfa Institute of Biomedical Sciences (AIBS), 9 Neapoleos St, 151 23 Marousi, Athens, Greece. E-mail: [email protected]
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
Pediatrics (2011) 128 (1): e169–e179.
Article history
Accepted:
January 24 2011
Citation
Elpis Mantadakis, Evridiki K. Vouloumanou, Georgia G. Georgantzi, Aggelos Tsalkidis, Αthanassios Chatzimichael, Matthew E. Falagas; Acute Tc-99m DMSA Scan for Identifying Dilating Vesicoureteral Reflux in Children: A Meta-analysis. Pediatrics July 2011; 128 (1): e169–e179. 10.1542/peds.2010-3460
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Diagnostic accuracy or risk factor value: the same variables but neither from the same perspective nor for similar purpose. Application in UTI in childhood.
Sir,
I greatly appreciated Mantadakis's article,1 and would like to complement this with a methodological comment on the strategy used to set an evidence-based and robust work up for imaging after urinary tract infection (UTI) in children. Until a recent past, attention has usually focused on vesicoureteral reflux (VUR), as the major factor for long-term complications of UTI. However, despite continuing debate, the most clinically relevant end-point is probably renal scarring, the presence of which is associated with worse renal outcomes in early adulthood. Selective approaches for UTI investigations reduce cost and distress, but misdiagnosis of the fewest possible patients with significant conditions remains the fundamental objective, as stated by the authors. In this global scheme, the authors addressed the research question of the diagnostic accuracy of early-phase renal DMSA for dilating VUR. Even thought the attempt of reducing and ordering UTI imaging work-up on a rational basis is valuable, I think the research question should not be raised as a diagnostic one. It would rather be better split into two separate questions: is dilating VUR a risk factor for renal scarring, then and if so, could a decision process or an algorithm on selective approaches for detecting renal scars be derived. The authors seem confused indeed: in one hand, they underwent a meta-analysis of diagnostic test accuracy of early-phase DMSA for dilating VUR, indicating that they expect both very good sensitivity and specificity in order to propose that DMSA can replace the current gold standard for VUR diagnostic, cystography. However, such proposition seems to me out of place: DMSA is a nuclear examination designed to analyze renal parenchymal involvement, not to visualize ureters of calyces in order to demonstrate VUR. However, in another hand, the authors also explain that their strategy is more directed towards a screening procedure rather than a definitive diagnostic test: they propose, as some others before, that cystography should be avoided in case of negative early-phase DMSA. This is more based on a risk factor value that indicates a relationship between acute pyelonephritis or renal scars as outcomes and dilating VUR as a predictor, rather than based on a diagnostic process.
Furthermore, it makes sense to first clarify if dilating VUR could be considered for sure as a risk factor. Meta-analyzing existing data is a quick and adapted tool to do so, even more that available data in the literature are conflicting. This step gives an answer at a population- level of course, but does not help the clinician at an individual-level when facing with his patients and the question of which imaging should be prescribed after UTI. The second step of the research process would help, deriving an algorithm ordering imaging based on the definition of a priori constraints of sensitivity or specificity. In the present case, reducing false negative results seems more important than minimizing false positives ones. Then, the algorithm would be derived in order to achieve at least a defined sensitivity, whatever the specificity obtained that only mirrors the number of imaging avoided. This step gives the useful individual-level response helping the clinician for patient care. Interestingly, meta-analysis could be cleverly used in the research question, as proposed by Sutton in trials network.2
Gordon et al. performed a very similar study in 2003, addressing the question of "is the finding of VUR on cystography would predict renal parenchymal disease".3 Surprisingly, the question is reverse compared to Mantadakis' study, possibly because VUR had more attention than renal scarring at that time in the literature than nowadays. For similar reasons as below in addition to the fact they mixed up early and late-phase DMSA together, they concluded the weakness of VUR as a predictor of renal involvement.
In conclusion, the most clinically relevant end-point is probably renal scarring, and selective approaches for UTI investigations are warranted to reduce cost and distress, but misdiagnosis of the fewest possible patients with significant conditions remains the fundamental objective, and thus requires a priori definition of constraints on high sensitivity when deriving models.4 This minimizes procedures but decreases specificity, although the latter does not need to be high since selectivity is only part of process. Future algorithms may therefore focus more on scarring, with less emphasis on VUR, once the relationship between VUR and scars has been demonstrated, to provide optimal individualized management and nephroprotection.
Sandrine Leroy, MD, PhD Epidemiology of Emerging Diseases Unit Institut Pasteur, Paris, France
References 1. Mantadakis E, Vouloumanou EK, Georgantzi GG, Tsalkidis A, Chatzimichael A, Falagas ME. Acute Tc-99m DMSA scan for identifying dilating vesicoureteral reflux in children: a meta-analysis. Pediatrics. 2011;128:e169-79.
2. Cooper NJ, Jones DR, Sutton AJ. The use of systematic reviews when designing studies. Clin Trials. 2005;2:260-4.
3. Gordon I, Barkovics M, Pindoria S, Cole TJ, Woolf AS. Primary vesicoureteric reflux as a predictor of renal damage in children hospitalized with urinary tract infection: a systematic review and meta- analysis. J Am Soc Nephrol. 2003;14:739-44.
4. Royston P, Moons KGM, Altman DG, Vergouwe Y. Developping a prognostic model. BMJ 2009;338:604.
Conflict of Interest:
None declared