Neonatal dexamethasone treatment in the rat leads to kidney damage in adulthood.
Recently, concern has been raised that corticosteroid treatment of preterm neonates might be associated with adverse effects later in life, including early development of hypertension. Here, we investigate the impact of neonatal dexamethasone (Dex) treatment on early renal cell proliferation and nephron number. We analyzed mitotic activity in renal cortex of rat pups neonatally treated with Dex. Nephron number was measured and possible renal damage was quantified by counting inflammatory foci, ED-1 positive cells (macrophages), and the desmin score (activated podocytes). Mitotic activity was 34 and 29% lower on d 2 and 4 in Dex-treated rats compared with saline-treated controls. The number of glomeruli was lower at 4 wk, but nephron size was unchanged after Dex treatment, as calculated from glomerular density and (lower) body- and kidney weight. At wk 50, the glomerular number was significantly lower in Dex-treated rats, whereas body and kidney weight were the same as in Sal controls. Dex rats also showed more kidney damage, manifested by a approximately 3.5-fold increase in inflammation foci/mm and in ED-1 positive cells/mm and a approximately 4.3-fold increased desmin score. Temporary suppression of mitotic activity during neonatal Dex treatment leads to reduction of nephron number and more kidney damage later in life.


BACKGROUND
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de Vries
Willem B
WB
Departments of Neonatology and Pathology, University Medical Center Utrecht/Wilhelmina Children's Hospital, Utrecht, 3508 AB, The Netherlands. w.b.devries-3@umcutrecht.nl
van den Borne
Pleunie
P
Goldschmeding
Roel
R
de Weger
Roel A
RA
Bal
Miriam P
MP
van Bel
Frank
F
van Oosterhout
Matthijs F M
MF
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D049109:Cell Proliferation; D003907:Dexamethasone / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D009929:Organ Size; D051381:Rats
D003907:Dexamethasone