Role of dexamethasone in controlling the proinflammatory cytokine cascade in the first episode of paediatric acute pyelonephritis

Acta Paediatr. 2024 Mar;113(3):564-572. doi: 10.1111/apa.17034. Epub 2023 Nov 15.

Abstract

Aim: Febrile urinary tract infection is a common bacterial infection in childhood. The kidney damage after acute pyelonephritis (APN) could be related to the stimulation of the proinflammatory response. We aimed to investigate the role of inflammatory cytokines and the effect of dexamethasone after a first episode of APN.

Methods: Subanalysis of the DEXCAR RCT in which children with confirmed APN (1 month-14 years) were randomly assigned to receive a 3 days course of either intravenous dexamethasone or placebo. Urinary cytokine levels at diagnosis and after 72 h of treatment were measured.

Results: Ninety-two patients were recruited. Younger patients, males and those with abnormalities in the ultrasound study or vesicoureteral reflux showed higher values of urinary cytokines. Patients with severe APN had higher Tumour Necrosis Factor (TNF)α levels (81.0 ± 75.8 vs. 33.6 ± 48.5 pg/mg creatinine, p = 0.015). Both intervention groups showed similar basal clinical characteristics, including urinary cytokine levels. Treatment reduced urinary cytokine levels irrespective of dexamethasone administration. Neither the intervention group nor the urinary cytokine levels modulated the development of kidney scars.

Conclusion: Basal urinary cytokines were associated with age, abnormal ultrasound and vesicoureteral reflux. Patients with severe APN had higher TNFa urinary levels. Administration of dexamethasone in children with APN does not improve the control of the proinflammatory cytokine cascade.

Keywords: acute pyelonephritis; corticosteroids; cytokines; kidney scarring.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acute Disease
  • Child
  • Cicatrix / complications
  • Cicatrix / pathology
  • Cytokines
  • Dexamethasone / therapeutic use
  • Humans
  • Infant
  • Kidney / pathology
  • Male
  • Pyelonephritis* / drug therapy
  • Urinary Tract Infections* / drug therapy
  • Vesico-Ureteral Reflux* / complications
  • Vesico-Ureteral Reflux* / drug therapy

Substances

  • Cytokines
  • Dexamethasone