Dexamethasone to prevent kidney scarring in acute pyelonephritis: a randomized clinical trial.
Acute pyelonephritis
Children
Corticosteroids
Kidney scar
Journal
Pediatric nephrology (Berlin, Germany)
ISSN: 1432-198X
Titre abrégé: Pediatr Nephrol
Pays: Germany
ID NLM: 8708728
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
received:
18
10
2021
accepted:
06
12
2021
revised:
04
12
2021
pubmed:
19
1
2022
medline:
27
7
2022
entrez:
18
1
2022
Statut:
ppublish
Résumé
Urinary tract infection (UTI) is one of the most common bacterial infections in childhood and is associated with long-term complications. We aimed to assess the effect of adjuvant dexamethasone treatment on reducing kidney scarring after acute pyelonephritis (APN) in children. Multicenter, prospective, double-blind, placebo-controlled, randomized clinical trial (RCT) where children from 1 month to 14 years of age with proven APN were randomly assigned to receive a 3-day course of either an intravenous corticosteroid (dexamethasone 0.30 mg per kg/day) twice daily or placebo. The late technetium 99 m-dimercaptosuric acid scintigraphy (> 6 months after acute episode) was performed to assess kidney scar persistence. Kidney scarring risk factors (vesicoureteral reflux, kidney congenital anomalies, or urinary tract dilatation) were also assessed. Ninety-one participants completed the follow-up and were finally included (dexamethasone n = 49 and placebo n = 42). Both groups had similar baseline characteristics. Twenty participants showed persistent kidney scarring after > 6 months of follow-up without differences in incidence between groups (22% and 21% in the dexamethasone and placebo groups, p = 0.907). Renal damage severity in the early DMSA (β = 0.648, p = 0.023) and procalcitonin values (β = 0.065 p = 0.027) significantly modulated scar development. Vesicoureteral reflux grade showed a trend towards significance (β = 0.545, p = 0.054), but dexamethasone treatment showed no effect. Dexamethasone showed no effect on reducing the risk of scar formation in children with APN. Hence, there is no evidence for an adjuvant corticosteroid treatment recommendation in children with APN. However, the study was limited by not achieving the predicted sample size and the expected scar formation. Clinicaltrials.gov, NCT02034851. Registered in January 14, 2014. "A higher resolution version of the Graphical abstract is available as Supplementary information."
Sections du résumé
BACKGROUND
Urinary tract infection (UTI) is one of the most common bacterial infections in childhood and is associated with long-term complications. We aimed to assess the effect of adjuvant dexamethasone treatment on reducing kidney scarring after acute pyelonephritis (APN) in children.
METHODS
Multicenter, prospective, double-blind, placebo-controlled, randomized clinical trial (RCT) where children from 1 month to 14 years of age with proven APN were randomly assigned to receive a 3-day course of either an intravenous corticosteroid (dexamethasone 0.30 mg per kg/day) twice daily or placebo. The late technetium 99 m-dimercaptosuric acid scintigraphy (> 6 months after acute episode) was performed to assess kidney scar persistence. Kidney scarring risk factors (vesicoureteral reflux, kidney congenital anomalies, or urinary tract dilatation) were also assessed.
RESULTS
Ninety-one participants completed the follow-up and were finally included (dexamethasone n = 49 and placebo n = 42). Both groups had similar baseline characteristics. Twenty participants showed persistent kidney scarring after > 6 months of follow-up without differences in incidence between groups (22% and 21% in the dexamethasone and placebo groups, p = 0.907). Renal damage severity in the early DMSA (β = 0.648, p = 0.023) and procalcitonin values (β = 0.065 p = 0.027) significantly modulated scar development. Vesicoureteral reflux grade showed a trend towards significance (β = 0.545, p = 0.054), but dexamethasone treatment showed no effect.
CONCLUSION
Dexamethasone showed no effect on reducing the risk of scar formation in children with APN. Hence, there is no evidence for an adjuvant corticosteroid treatment recommendation in children with APN. However, the study was limited by not achieving the predicted sample size and the expected scar formation.
TRIAL REGISTRATION
Clinicaltrials.gov, NCT02034851. Registered in January 14, 2014. "A higher resolution version of the Graphical abstract is available as Supplementary information."
Identifiants
pubmed: 35041042
doi: 10.1007/s00467-021-05398-w
pii: 10.1007/s00467-021-05398-w
pmc: PMC9307518
doi:
Substances chimiques
Technetium Tc 99m Dimercaptosuccinic Acid
494JNQ8L28
Dexamethasone
7S5I7G3JQL
Banques de données
ClinicalTrials.gov
['NCT02034851']
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2109-2118Informations de copyright
© 2021. The Author(s).
Références
Mattoo TK (2011) Vesicoureteral Reflux and Reflux Nephropathy. Adv Chronic Kidney Dis 18:348–354. https://doi.org/10.1053/j.ackd.2011.07.006
doi: 10.1053/j.ackd.2011.07.006
pubmed: 21896376
pmcid: 3169795
National Collaborating Centre for Women's and Children's Health, Commissioned by the National Institute for Health and Clinical Excellence. Urinary tract infection in under 162: diagnosis and management. https://www.nice.org.uk/guidance . Accesed 18 Oct 2021
Grupo de trabajo de la Guía de Práctica Clínica sobre Infección del Tracto Urinario en la Población Pediátrica. Guía de Práctica Clínica sobre Infección del Tracto Urinario en la Población Pediátrica. Plan de Calidad para el Sistema Nacional de Salud del Ministerio de Sanidad, Política Social e Igualdad. Instituto Aragonés de Ciencias de la Salud; 2011. Guías de Práctica Clínica en el SNS:I+CS No. 2009/01.
Shaikh N, Morone NE, Bost JE, Farrel MH (2008) Prevalence of urinary tract infection in childhood: A meta-analysis. Pediatr Infect Dis J 27:302–308. https://doi.org/10.1097/INF.0b013e31815e4122
doi: 10.1097/INF.0b013e31815e4122
pubmed: 18316994
Robinson JL, Finlay JC, Lang ME, Bortolussi R, Canadian Paediatric Society, Infectious Diseases and Immunization Committee, Community Paediatrics Committee (2014) Urinary tract infections in infants and children: Diagnosis and management. Paediatr Child Health 19:315–325. https://doi.org/10.1093/pch/19.6.315
doi: 10.1093/pch/19.6.315
pubmed: 25332662
pmcid: 4173959
Shaikh N, Craig JC, Rovers MM, Da Dalt L et al (2014) Identification of Children and Adolescents at Risk for Renal Scarring After a First Urinary Tract Infection A Meta-analysis With Individual Patient Data. JAMA Pediatr 168:893–900. https://doi.org/10.1001/jamapediatrics.2014.637
doi: 10.1001/jamapediatrics.2014.637
pubmed: 25089634
Mattoo TK, Shaikh N, Nelson CP (2021) Contemporary management of urinary tract infection in children. Pediatrics 147:e2020012138. https://doi.org/10.1542/peds.2020-012138
doi: 10.1542/peds.2020-012138
pubmed: 33479164
Hoen LA, Bogaert G, Radmayr C, Dogan HS et al (2021) Update of the EAU/ESPU guidelines on urinary tract infections in children. J Pediatr Urol 17:200–207. https://doi.org/10.1016/j.jpurol.2021.01.037
doi: 10.1016/j.jpurol.2021.01.037
pubmed: 33589366
Shaikh N, Ewing AL, Bhatnagar S, Hoberman A (2010) Risk of renal scarring in children with a first urinary tract infection: A systematic review. Pediatrics 126:1084–1091. https://doi.org/10.1542/peds.2010-0685
doi: 10.1542/peds.2010-0685
pubmed: 21059720
Park YS (2012) Renal scar formation after urinary tract infection in children. Korean J Pediatr 55:367–370. https://doi.org/10.3345/kjp.2012.55.10.367
doi: 10.3345/kjp.2012.55.10.367
pubmed: 23133482
pmcid: 3488611
Montini G, Tullus K, Hewitt I (2011) Febrile urinary tract infections in children. N Engl J Med 365:239–250. https://doi.org/10.1056/NEJMra1007755
doi: 10.1056/NEJMra1007755
pubmed: 21774712
Faust WC, Diaz M, Pohl HG (2009) Incidence of Post-Pyelonephritic Renal Scarring: A Meta-Analysis of the Dimercapto-Succinic Acid Literature. J Urol 181:290–298. https://doi.org/10.1016/j.juro.2008.09.039
doi: 10.1016/j.juro.2008.09.039
pubmed: 19013606
Mattoo TK, Chesney RW, Greenfield SP, Hoberman A et al (2016) Renal scarring in the randomized intervention for children with vesicoureteral reflux (RIVUR) trial. Clin J Am Soc Nephrol 11:54–61. https://doi.org/10.2215/CJN.05210515
doi: 10.2215/CJN.05210515
pubmed: 26555605
Snodgrass WT, Shah A, Yang M, Kwon J, Villanueva C, Traylor J, Pritzker K, Nakonezny PA, Haley RW, Bush NC (2013) Prevalence and risk factors for renal scars in children with febrile UTI and/or VUR: A cross-sectional observational study of 565 consecutive patients. J Pediatr Urol 9(6 PART A):856–863. https://doi.org/10.1016/j.jpurol.2012.11.019
doi: 10.1016/j.jpurol.2012.11.019
pubmed: 23465483
Pohl HG, Rushton HG, Park JS, Chandra R, Majd M (1999) Adjunctive oral corticosteroids reduce renal scarring: The piglet model of reflux and acute experimental pyelonephritis. J Urol 162:815–820. https://doi.org/10.1097/00005392-199909010-00067
doi: 10.1097/00005392-199909010-00067
pubmed: 10458387
Haraoka M, Matsumoto T, Takahashi K, Kubo S, Tanaka M, Kumzawa J (1994) Suppression of renal scarring by prednisolone combined with ciprofloxacin in ascending pyelonephritis in rats. J Urol 151:1078–1080. https://doi.org/10.1016/S0022-5347(17)35187-X
doi: 10.1016/S0022-5347(17)35187-X
pubmed: 8126797
Şener G, Tuğtepe H, Velioğlu-Oğunç A, Centinel S, Gedik N, Yeğen BC (2006) Melatonin prevents neutrophil-mediated oxidative injury in Escherichia coli-induced pyelonephritis in rats. J Pineal Res 41:220–227. https://doi.org/10.1111/j.1600-079X.2006.00357.x
doi: 10.1111/j.1600-079X.2006.00357.x
pubmed: 16948782
Biyikli NK, Tuǧtepe H, Şener G, Velioğlu-Oğunç A, Cetinel S, Midillioğlu S, Gedik N, Yeğen BC (2006) Oxytocin alleviates oxidative renal injury in pyelonephritic rats via a neutrophil-dependent mechanism. Peptides 27:2249–2257. https://doi.org/10.1016/j.peptides.2006.03.029
doi: 10.1016/j.peptides.2006.03.029
pubmed: 16707192
Huang A, Palmer LS, Hom D, Anderson AE, Kushner L, Franco I (1999) Ibuprofen combined with antibiotics suppresses renal scarring due to ascending pyelonephritis in rats. J Urol 162:1396–1398. https://doi.org/10.1016/S0022-5347(05)68319-X
doi: 10.1016/S0022-5347(05)68319-X
pubmed: 10492222
Huang YY, Chen MJ, Chiu NT, Chou HH, Lin KY, Chiou YY (2011) Adjunctive oral methylprednisolone in pediatric acute pyelonephritis alleviates renal scarring. Pediatrics 128:e496–e504. https://doi.org/10.1542/peds.2010-0297
doi: 10.1542/peds.2010-0297
pubmed: 21844061
Ghaffari J, Mohammad-Jafari H, Mohammadi G, Mahdavi MR (2019) Assessment the effect of dexamethasone on urinary cytokines and renal scar in children with acute pyelonephritis. Iran J Kidney Dis 13:244–250
pubmed: 31422390
Shaikh N, Shope TR, Hoberman A, Muniz GB et al (2020) Corticosteroids to prevent kidney scarring in children with a febrile urinary tract infection: a randomized trial. Pediatr Nephrol 35:2113–2120. https://doi.org/10.1007/s00467-020-04622-3
doi: 10.1007/s00467-020-04622-3
pubmed: 32556960
pmcid: 7529851
Brouwer MC, Mcintyre P, Prasad K, van de Beek D (2015) Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev 9:CD004405. https://doi.org/10.1002/14651858.CD004405.pub5
doi: 10.1002/14651858.CD004405.pub5
Piñeiro Pérez R, Cilleruelo Ortega MJ, Ares Álvarez J, Baquero-Artigao F et al (2019) Recomendaciones sobre el diagnóstico y tratamiento de la infección urinaria. An Pediatra (Barc) 90:400.e1-400.e9
doi: 10.1016/j.anpedi.2019.02.009
Piepsz A, Colarinha P, Gordon I, Hahn K, Olivier P, Roca I, Sixt R, van Velzen J, Paediatric Committee of the European Association of Nuclear Medicine (2009) Guidelines on 99mTc-DMSA Scintigraphy in children. Eur J Nucl Med 28:37–41
Keren R, Carpenter MA, Hoberman A, Shaikh N et al (2008) Rationale and design issues of the randomized intervention for children with vesicoureteral reflux (RIVUR) study. Pediatrics 122:S240–S250. https://doi.org/10.1542/peds.2008-1285d
doi: 10.1542/peds.2008-1285d
pubmed: 19018048
Palacios Loro ML, Segura Ramírez DK, Ordoñez Álvarez FA, Santos Rodríguez F (2016) Congenital anomalies of the kidney and urinary tract. An Pediatr 17:e18–e27. https://doi.org/10.1542/neo.17-1-e18
doi: 10.1542/neo.17-1-e18
Nguyen HT, Benson CB, Bromley B, Campbell JB et al (2014) Multidisciplinary consensus on the classification of prenatal and postnatal urinary tract dilatation (UTD classification system). J Pediatr Urol 10:982–998
doi: 10.1016/j.jpurol.2014.10.002
Lebowitz RL, Olbing H, Parkkulainen KV, Smellie JM, Tamminen-Möbius TE (1985) International system of radiographic grading of vesicoureteric reflux. Pediatr Radiol 15:105–109. https://doi.org/10.1007/BF02388714
doi: 10.1007/BF02388714
pubmed: 3975102
Schulz KF, Altman DG, Moher D (2010) CONSORT 2010 Statement Updated Guidelines for Reporting Parallel Group Randomized Trials Background to CONSORT. Mayo Clin Coll Med 115:1097. https://doi.org/10.1097/AOG.0b013e3181d9d421
doi: 10.1097/AOG.0b013e3181d9d421
Pecile P, Miorin E, Romanello C, Vidal E, Contardo M, Valent F, Tenore A (2009) Age-related renal parenchymal lesions in children with first febrile urinary tract infections. Pediatrics 124:23–29. https://doi.org/10.1542/peds.2008-1192
doi: 10.1542/peds.2008-1192
pubmed: 19564279
Keren R, Shaikh N, Pohl H, Gravens-Mueller L et al (2015) Risk factors for recurrent urinary tract infection and renal scarring. Pediatrics 136:e13–e21. https://doi.org/10.1542/peds.2015-0409
doi: 10.1542/peds.2015-0409
pubmed: 26055855
pmcid: 4485012
Swerkersson S, Jodal U, Sixt R, Stoklaend E, Hansson S (2017) Urinary tract infection in small children: the evolution of renal damage over time. Pediatr Nephrol 32:1907–1913. https://doi.org/10.1007/s00467-017-3705-5
doi: 10.1007/s00467-017-3705-5
pubmed: 28681079
pmcid: 5579136
Lee YJ, Lee JH, Park YS (2012) Risk factors for renal scar formation in infants with first episode of acute pyelonephritis: A prospective clinical study. J Urol 187:1032–1036. https://doi.org/10.1016/j.juro.2011.10.164
doi: 10.1016/j.juro.2011.10.164
pubmed: 22264451
Orellana P, Baquedano P, Rangarajan V, Zhao JH et al (2004) Relationship between acute pyelonephritis, renal scarring, and vesicoureteral reflux. Results of a coordinated research project. Pediatr Nephrol 19:1122–1126. https://doi.org/10.1007/s00467-004-1501-5
doi: 10.1007/s00467-004-1501-5
pubmed: 15258842
Shaikh N, Mattoo TK, Keren R, Ivanova A, Cui G, Moxey-Mims M, Majd M, Ziessman HA, Hoberman A (2016) Early antibiotic treatment for pediatric febrile urinary tract infection and renal scarring. JAMA Pediatr 170:848–854. https://doi.org/10.1001/jamapediatrics.2016.1181
doi: 10.1001/jamapediatrics.2016.1181
pubmed: 27455161
Leroy S, Fernández-López A, Nikfar R, Romanello C et al (2013) Association of procalcitonin with acute pyeloneprhitis and renal scars in pediatric UTI. Pediatrics: 131870-879. https://doi.org/10.1542/peds.2012-2408