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

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.

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

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 (ß = 0.648, p = 0.023) and procalcitonin values (ß = 0.065 p = 0.027) significantly modulated scar development. Vesicoureteral reflux grade showed a trend towards significance (ß = 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."