Dexamethasone to prevent kidney scarring in acute pyelonephritis: a randomized clinical trial

Neus Rius-Gordillo, Natàlia Ferré, Juan David González, Zaira Ibars, Ester Parada-Ricart, Maria Gloria Fraga, Sara Chocron, Manuel Samper, Carmen Vicente, Jordi Fuertes, Joaquín Escribano, DEXCAR Study Group, Neus Rius-Gordillo, Natàlia Ferré, Juan David González, Zaira Ibars, Ester Parada-Ricart, Maria Gloria Fraga, Sara Chocron, Manuel Samper, Carmen Vicente, Jordi Fuertes, Joaquín Escribano, DEXCAR Study Group

Abstract

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."

Keywords: Acute pyelonephritis; Children; Corticosteroids; Kidney scar.

Conflict of interest statement

The authors declare no competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Flow chart
Fig. 2
Fig. 2
Kidney scar development and severity according to treatment group

References

    1. Mattoo TK. Vesicoureteral Reflux and Reflux Nephropathy. Adv Chronic Kidney Dis. 2011;18:348–354. doi: 10.1053/j.ackd.2011.07.006.
    1. 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. . Accesed 18 Oct 2021
    1. 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.
    1. Shaikh N, Morone NE, Bost JE, Farrel MH. Prevalence of urinary tract infection in childhood: A meta-analysis. Pediatr Infect Dis J. 2008;27:302–308. doi: 10.1097/INF.0b013e31815e4122.
    1. Robinson JL, Finlay JC, Lang ME, Bortolussi R, Canadian Paediatric Society, Infectious Diseases and Immunization Committee, Community Paediatrics Committee Urinary tract infections in infants and children: Diagnosis and management. Paediatr Child Health. 2014;19:315–325. doi: 10.1093/pch/19.6.315.
    1. Shaikh N, Craig JC, Rovers MM, Da Dalt L, et al. 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. 2014;168:893–900. doi: 10.1001/jamapediatrics.2014.637.
    1. Mattoo TK, Shaikh N, Nelson CP. Contemporary management of urinary tract infection in children. Pediatrics. 2021;147:e2020012138. doi: 10.1542/peds.2020-012138.
    1. Hoen LA, Bogaert G, Radmayr C, Dogan HS, et al. Update of the EAU/ESPU guidelines on urinary tract infections in children. J Pediatr Urol. 2021;17:200–207. doi: 10.1016/j.jpurol.2021.01.037.
    1. Shaikh N, Ewing AL, Bhatnagar S, Hoberman A. Risk of renal scarring in children with a first urinary tract infection: A systematic review. Pediatrics. 2010;126:1084–1091. doi: 10.1542/peds.2010-0685.
    1. Park YS. Renal scar formation after urinary tract infection in children. Korean J Pediatr. 2012;55:367–370. doi: 10.3345/kjp.2012.55.10.367.
    1. Montini G, Tullus K, Hewitt I. Febrile urinary tract infections in children. N Engl J Med. 2011;365:239–250. doi: 10.1056/NEJMra1007755.
    1. Faust WC, Diaz M, Pohl HG. Incidence of Post-Pyelonephritic Renal Scarring: A Meta-Analysis of the Dimercapto-Succinic Acid Literature. J Urol. 2009;181:290–298. doi: 10.1016/j.juro.2008.09.039.
    1. Mattoo TK, Chesney RW, Greenfield SP, Hoberman A, et al. Renal scarring in the randomized intervention for children with vesicoureteral reflux (RIVUR) trial. Clin J Am Soc Nephrol. 2016;11:54–61. doi: 10.2215/CJN.05210515.
    1. Snodgrass WT, Shah A, Yang M, Kwon J, Villanueva C, Traylor J, Pritzker K, Nakonezny PA, Haley RW, Bush NC. 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. 2013;9(6 PART A):856–863. doi: 10.1016/j.jpurol.2012.11.019.
    1. Pohl HG, Rushton HG, Park JS, Chandra R, Majd M. Adjunctive oral corticosteroids reduce renal scarring: The piglet model of reflux and acute experimental pyelonephritis. J Urol. 1999;162:815–820. doi: 10.1097/00005392-199909010-00067.
    1. Haraoka M, Matsumoto T, Takahashi K, Kubo S, Tanaka M, Kumzawa J. Suppression of renal scarring by prednisolone combined with ciprofloxacin in ascending pyelonephritis in rats. J Urol. 1994;151:1078–1080. doi: 10.1016/S0022-5347(17)35187-X.
    1. Şener G, Tuğtepe H, Velioğlu-Oğunç A, Centinel S, Gedik N, Yeğen BC. Melatonin prevents neutrophil-mediated oxidative injury in Escherichia coli-induced pyelonephritis in rats. J Pineal Res. 2006;41:220–227. doi: 10.1111/j.1600-079X.2006.00357.x.
    1. Biyikli NK, Tuǧtepe H, Şener G, Velioğlu-Oğunç A, Cetinel S, Midillioğlu S, Gedik N, Yeğen BC. Oxytocin alleviates oxidative renal injury in pyelonephritic rats via a neutrophil-dependent mechanism. Peptides. 2006;27:2249–2257. doi: 10.1016/j.peptides.2006.03.029.
    1. Huang A, Palmer LS, Hom D, Anderson AE, Kushner L, Franco I. Ibuprofen combined with antibiotics suppresses renal scarring due to ascending pyelonephritis in rats. J Urol. 1999;162:1396–1398. doi: 10.1016/S0022-5347(05)68319-X.
    1. Huang YY, Chen MJ, Chiu NT, Chou HH, Lin KY, Chiou YY. Adjunctive oral methylprednisolone in pediatric acute pyelonephritis alleviates renal scarring. Pediatrics. 2011;128:e496–e504. doi: 10.1542/peds.2010-0297.
    1. Ghaffari J, Mohammad-Jafari H, Mohammadi G, Mahdavi MR. Assessment the effect of dexamethasone on urinary cytokines and renal scar in children with acute pyelonephritis. Iran J Kidney Dis. 2019;13:244–250.
    1. Shaikh N, Shope TR, Hoberman A, Muniz GB, et al. Corticosteroids to prevent kidney scarring in children with a febrile urinary tract infection: a randomized trial. Pediatr Nephrol. 2020;35:2113–2120. doi: 10.1007/s00467-020-04622-3.
    1. Brouwer MC, Mcintyre P, Prasad K, van de Beek D. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev. 2015;9:CD004405. doi: 10.1002/14651858.CD004405.pub5.
    1. Piñeiro Pérez R, Cilleruelo Ortega MJ, Ares Álvarez J, Baquero-Artigao F, et al. Recomendaciones sobre el diagnóstico y tratamiento de la infección urinaria. An Pediatra (Barc) 2019;90:400.e1–400.e9. doi: 10.1016/j.anpedi.2019.02.009.
    1. 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 Guidelines on 99mTc-DMSA Scintigraphy in children. Eur J Nucl Med. 2009;28:37–41.
    1. Keren R, Carpenter MA, Hoberman A, Shaikh N, et al. Rationale and design issues of the randomized intervention for children with vesicoureteral reflux (RIVUR) study. Pediatrics. 2008;122:S240–S250. doi: 10.1542/peds.2008-1285d.
    1. Palacios Loro ML, Segura Ramírez DK, Ordoñez Álvarez FA, Santos Rodríguez F. Congenital anomalies of the kidney and urinary tract. An Pediatr. 2016;17:e18–e27. doi: 10.1542/neo.17-1-e18.
    1. Nguyen HT, Benson CB, Bromley B, Campbell JB, et al. Multidisciplinary consensus on the classification of prenatal and postnatal urinary tract dilatation (UTD classification system) J Pediatr Urol. 2014;10:982–998. doi: 10.1016/j.jpurol.2014.10.002.
    1. Lebowitz RL, Olbing H, Parkkulainen KV, Smellie JM, Tamminen-Möbius TE. International system of radiographic grading of vesicoureteric reflux. Pediatr Radiol. 1985;15:105–109. doi: 10.1007/BF02388714.
    1. Schulz KF, Altman DG, Moher D. CONSORT 2010 Statement Updated Guidelines for Reporting Parallel Group Randomized Trials Background to CONSORT. Mayo Clin Coll Med. 2010;115:1097. doi: 10.1097/AOG.0b013e3181d9d421.
    1. Pecile P, Miorin E, Romanello C, Vidal E, Contardo M, Valent F, Tenore A. Age-related renal parenchymal lesions in children with first febrile urinary tract infections. Pediatrics. 2009;124:23–29. doi: 10.1542/peds.2008-1192.
    1. Keren R, Shaikh N, Pohl H, Gravens-Mueller L, et al. Risk factors for recurrent urinary tract infection and renal scarring. Pediatrics. 2015;136:e13–e21. doi: 10.1542/peds.2015-0409.
    1. Swerkersson S, Jodal U, Sixt R, Stoklaend E, Hansson S. Urinary tract infection in small children: the evolution of renal damage over time. Pediatr Nephrol. 2017;32:1907–1913. doi: 10.1007/s00467-017-3705-5.
    1. Lee YJ, Lee JH, Park YS. Risk factors for renal scar formation in infants with first episode of acute pyelonephritis: A prospective clinical study. J Urol. 2012;187:1032–1036. doi: 10.1016/j.juro.2011.10.164.
    1. Orellana P, Baquedano P, Rangarajan V, Zhao JH, et al. Relationship between acute pyelonephritis, renal scarring, and vesicoureteral reflux. Results of a coordinated research project. Pediatr Nephrol. 2004;19:1122–1126. doi: 10.1007/s00467-004-1501-5.
    1. Shaikh N, Mattoo TK, Keren R, Ivanova A, Cui G, Moxey-Mims M, Majd M, Ziessman HA, Hoberman A. Early antibiotic treatment for pediatric febrile urinary tract infection and renal scarring. JAMA Pediatr. 2016;170:848–854. doi: 10.1001/jamapediatrics.2016.1181.
    1. 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. 10.1542/peds.2012-2408

Source: PubMed

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