The magnitude of nephron number reduction mediates intrauterine growth-restriction-induced long term chronic renal disease in the rat. A comparative study in two experimental models

BACKGROUND: Intrauterine growth restriction (IUGR) is a risk factor for hypertension (HT) and chronic renal disease (CRD). A reduction in the nephron number is proposed to be the underlying mechanism; however, the mechanism is debated. The aim of this study was to demonstrate that IUGR-induced HT and CRD are linked to the magnitude of nephron number reduction, independently on its cause.

METHODS: Systolic blood pressure (SBP), glomerular filtration rate (GFR), proteinuria, nephron number, and glomerular sclerosis were compared between IUGR offspring prenatally exposed to a maternal low-protein diet (9% casein; LPD offspring) or maternal administration of betamethasone (from E17 to E19; BET offspring) and offspring with a normal birth weight (NBW offspring).

RESULTS: Both prenatal interventions led to IUGR and a similar reduction in birth weight. In comparison to NBW offspring, BET offspring had a severe nephron deficit (-50% in males and -40% in females, p < 0.01), an impaired GFR (-33%, p < 0.05), and HT (SBP+ 17 mmHg, p < 0.05). Glomerular sclerosis was more than twofold higher in BET offspring than in NBW offspring (p < 0.05). Long-term SBP, GFR, and glomerular sclerosis were unchanged in LPD offspring while the nephron number was moderately reduced only in males (-28% vs. NBW offspring, p < 0.05).

CONCLUSION: In this study, the magnitude of nephron number reduction influences long term renal disease in IUGR offspring: a moderate nephron number is an insufficient factor. Extremely long-term follow-up of adults prenatally exposed to glucocorticoids are required.

Medienart:

E-Artikel

Erscheinungsjahr:

2016

Erschienen:

2016

Enthalten in:

Zur Gesamtaufnahme - volume:14

Enthalten in:

Journal of translational medicine - 14(2016), 1 vom: 30. Nov., Seite 331

Sprache:

Englisch

Beteiligte Personen:

Boubred, Farid [VerfasserIn]
Daniel, Laurent [VerfasserIn]
Buffat, Christophe [VerfasserIn]
Tsimaratos, Michel [VerfasserIn]
Oliver, Charles [VerfasserIn]
Lelièvre-Pégorier, Martine [VerfasserIn]
Simeoni, Umberto [VerfasserIn]

Themen:

9842X06Q6M
Betamethasone
Chronic kidney disease
Comparative Study
Glomerular sclerosis
Hypertension
IUGR
Journal Article
Low birth weight
Nephron number
Prenatal glucocorticoids
Preterm infant
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 16.10.2017

Date Revised 13.11.2018

published: Electronic

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM266658830