title: Neonatal dexamethasone administration causes progressive renal damage due to induction of an early inflammatory response.
abstract: Glucocorticoids (GCs) are widely used to prevent chronic lung disease in immature newborns. Emerging evidence indicates that GC exposure in early life may interfere with kidney function and is associated with hypertension in later life. In this study, we have investigated the effect of neonatal dexamethasone (DEX) administration on renal function in rats. Male rats were treated with DEX in the first 3 days after birth, controls received saline (SAL). Severe renal damage associated with premature death was found at 50 wks upon DEX treatment, while renal function and morphology were normal in controls. A subsequent time-course study was performed from 2 days to 32 wks. Compared with controls, neonatal DEX administration led to significant and persistent growth retardation. Progressive proteinuria and increased systolic blood pressure were found from 8 wks onwards in DEX-treated animals. Renal alpha-SMA gene expression was elevated from wk 24 onwards and morphological fibrosis was noted at 32 wks of age following DEX treatment. Markedly increased renal gene expression of TNF-alpha and MCP-1 in DEX -treated rats was observed at day 7, probably contributing to the permanent increase in interstitial macrophage numbers that started at 14 days. Permanently elevated renal TGF-beta gene expression was induced by DEX administration from 4 wks onwards. Our data indicate that neonatal DEX administration in rats leads to renal failure in later life, presumably due to an early inflammatory trigger that elicits a persistent pro-fibrotic process that eventually results in progressive renal deterioration.
authors.affiliation: Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
authors.forename: Rick
authors.initials: R
authors.lastname: Havinga
authors.forename: Julius F W
authors.initials: JF
authors.lastname: Baller
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Bloks
authors.forename: Feike R
authors.initials: FR
authors.lastname: van der Leij
authors.forename: Pieter J J
authors.initials: PJ
authors.lastname: Sauer
authors.forename: Folkert
authors.initials: F
authors.lastname: Kuipers
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.forename: Martin H
authors.initials: MH
authors.lastname: de Borst
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D007249:Inflammation / Q000139:chemically induced*; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D008297:Male; D009399:Nephrons / Q000187:drug effects / Q000473:pathology; D011247:Pregnancy; D011507:Proteinuria / Q000139:chemically induced; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D003907:Dexamethasone