Research Article|Articles in Press

How the 99mTc-DMSA scintigraphy findings are reflected in the adopted treatment of primary vesicoureteral reflux: One centre experience

Published:February 12, 2023DOI:



      Renal changes may have long-term sequalae and prevention is a main goal of management of primary vesicoureteral reflux (VUR).


      This study aims to reveal how much 99mTc-DMSA scintigraphy findings are reflected in the adopted surgical or non-surgical treatment in children with diagnosed primary VUR and to give the clinicians information regarding their final therapeutic decision.

      Patients and methods

      A total 207 children with primary VUR who underwent non-acute 99mTc-DMSA scan were retrospectively evaluated. The presence of renal changes, their grading, differential function asymmetry (<45%) and grade of VUR were compared with subsequent choice of therapy.


      Altogether 92 (44%) children had asymmetric differential function, 122 (59%) showed presence of renal changes, 79 (38%) had high-grade VUR (IV-V). Patients with renal changes had lower differential function (41%vs.48%) and higher grade of VUR. The incidence of high-grade changes (G3+G4B) afflicting more than one third of the kidney was significantly different between grade I-II, III and IV-V VUR (9%, 27%, 48%, respectively). Renal changes were detected in 76% of surgically and 48% of non-surgically treated patients, high-grade 99mTc-DMSA changes in 69% and 31%, respectively. In children with no scars/dysplasia (G0+G4A), non-surgical treatment prevailed in 77%. The independent predictors for surgical intervention were presence of renal changes and higher grade of VUR, but not functional asymmetry.


      Over the last 20 years, there has been a shift toward more non-surgical management of VUR. The long-term outcome of this approach should be thoroughly studied. This is the first study analysing renal status in VUR patients using 99mTc-DMSA scan and its grading regarding the adopted treatment. Renal changes in almost half of non-surgically treated children with VUR should be an indicator for earlier diagnosis and effective treatment of acute pyelonephritis and VUR. We recommend distinguishing grade III VUR, as a moderate-grade VUR, because it is linked to higher incidence of high-grade 99mTc-DMSA changes (G3+G4B); our findings of 65% of grade III VURs treated non-surgically should be cautionary. Grade III VUR does not mean a low-risk condition and should alert the clinician to evaluate the extent of renal changes and unmask high-risk cases.


      Summary TableRelationship between 99mTc-DMSA scan grading and choice of treatment.
      99mTc-DMSA scan grading Conservative n = 124 Surgery n = 83 All n = 207
      G0 64 (75%) 21 (25%) 85 (41%)
      G1 18 (67%) 9 (33%) 27 (13%)
      G2 7 (50%) 7 (50%) 14 (7%)
      G3 5 (20%) 20 (80%) 25 (12%)
      G4A 15 (88%) 2 (12%) 17 (8%)
      G4B 15 (38%) 24 (62%) 39 (19%)
      G1+G2+G3+G4B1) 45 (43%) 60 (57%) 105 (51%)
      G0+G4A1) 79 (77%) 23 (23%) 102 (49%)
      G3+G4B1) 20 (31%) 44 (69%) 64 (31%)
      1)p < 0.0001 (Fisher's test).


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        • Keren R.
        • Shaikh N.
        • Pohl H.
        • Gravens-Mueller L.
        • Ivanova A.
        • Zaoutis L.
        • et al.
        Risk factors for recurrent urinary tract infection and renal scarring.
        Pediatrics. 2015; 136: e13-e21
        • Läckgren G.
        • Cooper C.S.
        • Neveus T.
        • Kirsch A.J.
        Management of vesicoureteral reflux: what have we learned over the last 20 years?.
        Front Pediatr. 2021; 9
        • Mathias S.
        • Greenbaum L.A.
        • Shubha A.M.
        • Raj J.A.M.
        • Das K.
        • Pais P.
        • et al.
        Risk factors for renal scarring and clinical morbidity in children with high-grade and low-grade primary vesicoureteral reflux.
        J Pediatr Urol. 2022; 8: S1477-S5131(22)00002-X
        • Peters C.
        • Rushton H.G.
        Vesicoureteral reflux associated renal damage: congenital reflux nephropathy and acquired renal scarring.
        J Urol. 2010; 184: 265-273
        • Faust W.C.
        • Diaz M.
        • Pohl H.G.
        Incidence of post-pyelonephritic renal scarring: a meta-analysis of the dimercapto-succinic acid literature.
        J Urol. 2009 Jan; 181: 270-297
        • Piepsz A.
        • Blaufox M.D.
        • Gordon I.
        • Granerus G.
        • Majd M.
        • O´ Reilly P.
        • et al.
        Consensus on renal cortical scintigraphy in children with urinary infection. Scientific committee of radionuclides in nephron-urology.
        Semin Nucl Med. 1999; 29: 160-174
        • Craig J.C.
        • Irwig L.M.
        • Howman-Giles R.B.
        • Uren R.F.
        • Bernard E.J.
        • Knight J.F.
        • et al.
        Variability in the interpretation of dimercaptosuccinic acid scintigraphy after urinary tract infection in children.
        J Nucl Med. 1998; 39: 1428-1432
        • Arnold A.J.
        • Brownless S.M.
        • Carty H.M.
        • Rickwood A.M.
        Detection of renal scarring by DMSA scanning-an experimental study.
        J Pediatr Surg. 1990; 25: 391-393
        • Sfakianakis G.N.
        • Sfakianakis E.D.
        Nuclear medicine pediatric urology and nephrology.
        J Nucl Med. 1988; 29: 1287-1300
        • Chen M.J.
        • Cheng H.L.
        • Chiou Y.Y.
        Risk factors for renal scarring and deterioration of renal function in primary vesicoureteral reflux children: a long-term follow-up retrospective cohort study.
        PLoS One. 2013; 8e57954
        • Gordon I.
        • Barkovics M.
        • Pindoria S.
        • Cole T.J.
        • Woolf S.
        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: 739-744
        • Hong I.K.
        • Chung M.H.
        • Bin J.H.
        • Lee K.Y.
        • Kim J.S.
        • Kim C.H.
        • et al.
        Prediction of vesicoureteral reflux in children with febrile urinary tract infection using relative uptake and cortical defect in DMSA scan.
        Pediatr and Neonatol. 2018; 59: 618-623
        • Tekgül S.
        • Riedmiller H.
        • Hoebeke P.
        • Kočvara R.
        • Nijman R.J.
        • Radmayr C.
        • et al.
        EAU guidelines on vesicoureteral reflux in children.
        Eur Urol. 2012; 62: 534-554
        • Snodgrass W.T.
        • Shah A.
        • Yang M.
        • Kwon J.
        • Villanueva C.
        • Traylor J.
        • et al.
        Prevalence and risk factors for renal scars in children with febrile UTI and/or VUR: a cross-sectional observation study of 565 consecutive patients.
        J Pediatr Urol. 2013; 9: 856-866
      1. National Collaborating Centre for Women’s and Children’s Health. National Institute for health and clinical excellence (NICE) guideline. Urinary tract infection in children: diagnosis, treatment, and long-term management [Internet]. Available from:; RCOG press at the royal college of obstetricians and gynaecologists, London 2007, 2017 (accessed May 2022).

      2. Craig A, Peters CA, Skoog SJ, Arant BS, Coop HL, Elder JS, et al. Management and screening of primary vesicoureteral reflux in children (2010, amended 2017)-AUA Guideline. Available at: (accessed May 2022).

        • Breinbjerg A.
        • Siggaard Jorgensen C.
        • Tullus K.
        • Kamperis K.
        • Rittig S.
        Risk factors for kidney scarring and vesicoureteral reflux in 421 children after their first acute pyelonephritis, and appraisal of international guidelines.
        Pediatr Nephrol. 2021; 36: 2777-2787
        • Lassmann M.
        • Treves S.T.
        Paediatric Dosage Harmonization Working Group. Paediatric radiopharmaceutical administration: harmonization of the 2007 EANM paediatric dosage card (version 1.5. 2008) and the 2010 North American consensus guidelines.
        Eur J Nucl Med Mol Imaging. 2014; 41: 1036-1041
      3. Piepsz A, Colarinha P, Gordon I, Hahn K, Olivier P, Roca I, et al. Revised guidelines on 99m Tc-DMSA scintigraphy in children (2009) original version published in: Eur J Nucl Med. 2001 Mar;28(3):BP37-41. (accessed September 2022).

        • Mattoo T.K.
        • Chesney R.W.
        • Greenfield S.P.
        • Hoberman A.
        • Keren R.
        • Mathews R.
        • et al.
        Renal scaring in the randomized intervention for children with vesicoureteral reflux. (RIVUR) trial.
        Clin J Am Soc Nephrol. 2016 Jan 7; 11: 54-61
        • Roupakias S.
        • Sinopidis X.
        • Tsikopoulos G.
        • Spyridakis I.
        • Katarza A.
        • Varvagiou A.
        Dimercaptosuccinic acid scan challenges in childhood urinary tract infection, vesicoureteral reflux and renal scarring investigation and management.
        Minerva Urol Nefrol. 2017; 69: 144-152
        • Swerkesson S.
        • Jodal U.
        • Sixt R.
        • Stokland E.
        • Hansson S.
        Relationship among vesicoureteral reflux, urinary tract infection and renal damage in children.
        J Urol. 2007 Aug; 178 (51discussion 650-1): 647
        • Loukogeorgakis S.P.
        • Burnand K.
        • MacDonald A.
        • Wessely K.
        • De Caluwe D.
        • Rahman N.
        • et al.
        Renal scarring is the most significant predictor of breakthrough febrile urinary tract infection in patients with simplex and duplex primary vesico-ureteral reflux.
        J Pediatr Urol. 2020 Apr; 16: 189.e1-189.e7
        • Nepple K.G.
        • Knudson M.J.
        • Austin J.C.
        • Cooper C.S.
        Abnormal renal scans and decreased early resolution of low-grade vesicoureteral reflux.
        J Urol. 2008; 180 (discussion 7): 1643-1647
        • Lee H.
        • Choi J.H.
        • Kang D.H.
        • Kim S.
        • Kang K.S.
        • Han K.H.
        Predictive markers for screening renal damage in children with urinary tract infections and vesicoureteral reflux.
        Child Kidney Dis. 2020; 24: 27-35
        • Mingin G.C.
        • Nguyen H.T.
        • Baskin L.S.
        • Susan Harlan
        Abnormal dimercapto-succinic acid scans predict an increased risk of breakthrough infection in children with vesicoureteral reflux.
        J Urol. 2004; 172: 1075-1077
        • Silva J.M.P.
        • Silverio J.
        • Diniz S.
        • Lima E.M.
        • Vergara R.M.
        • Oliveria E.A.
        Predictive factors of resolution of primary vesico-ureteric reflux: a multivariate analysis.
        BJU Int. 2006 May; 97: 1063-1068
        • Matsuoka H
        • Tanaka M
        • amaguchi T
        • Miyazato M
        • Kihara T
        • Nakagawa M
        • et al.
        The long-term prognosis of nephropathy in operated reflux.
        J Pediatr Urol. 2019 Dec; 15: 605.e1-e8
        • Garcia-Roig M.
        • Travers C.
        • McCracken C.E.
        • Kirsch A.J.
        National trends in the management of primary vesicoureteral reflux in children.
        J Urol. 2018; 199: 287-293
        • Lee T.
        • Varda B.K.
        • Venna A.
        • McCarthy I.
        • Logvinenko T.
        • Nelson C.P.
        Changes in clinical presentation and renal outcomes among children with febrile urinary tract infection. 2005 vs 2015.
        J Urol. 2021; 205: 1764-1769
        • Bosakova A.
        • Salounova D.
        • Havelka J.
        • Kraft O.
        • Sirucek P.
        • Kocvara R.
        • et al.
        Diffusion weighed magnetic resonance imaging is more sensitive than dimercaptosuccinic acid scintigraphy in detecting parenchymal lesions in children with acute pyelonephritis: a prospective study.
        J Pediatr Urol. 2018; 14: 269.e7

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