Abstract The outcome of ischemic acute renal failure
(IARF) is better in young than adult rats. Insulin-like
growth factor I (IGF-I) treatment may increase mortality
of adult rats with IARF, probably because of an exagger-
ated inflammatory response. We report the response to
IGF-I therapy in young rats with IARF. Male rats, aged
28±1 days, with IARF were given subcutaneous IGF-I,
50 μg/100 g at 0, 8, and 16 h after reperfusion (IGF) or
were untreated (ARF). Sham-operated rats were used as
controls. At 2 and 7 days after ischemia, serum urea ni-
trogen and histological damage score, cell proliferation,
apoptosis, neutrophil infiltration, and IGF-I receptor
mRNA in kidneys were analyzed. The degree of renal
failure, mortality rate, histological damage, cell prolifer-
ation, and neutrophil infiltration were not different be-
tween IGF-I and ARF rats. Hence, short-term IGF-I
treatment did not modify the course of IARF in young
rats.
Keywords Acute renal failure · Ischemia · Rat ·
Insulin-like growth factor-I · Neutrophil · Inflammation
Introduction
Acute renal failure (ARF) is defined as a sudden decline
of renal function with resultant accumulation of poten-
tially toxic metabolic substances. The reduction in glom-
erular filtration rate, together with ARF-induced exacer-
bation of protein catabolism [1, 2], leads to retention of
nitrogenous waste products and, subsequently, to elevat-
ed serum levels of creatinine and urea nitrogen (SUN)
[3].
Although the incidence of ARF in the pediatric popu-
lation is about a fifth of that found in adults [3, 4], it re-
mains a significant problem in children. It accounts for
0.2% of pediatric admissions in tertiary referral chil-
dren’s hospitals [5], and in neonates and small infants
the incidence is comparable to that of adults [6, 7, 8, 9].
The introduction of dialysis in the treatment of ARF in
the 1950s reduced overall mortality caused by this syn-
drome from 80% to 25% [10]. Since then, the mortality
rate has remained substantially invariable [4, 11, 12] in
spite of the multiple technological and pharmacological
advancements in the treatment of these patients [3, 13].
Although the etiology of ARF is frequently multifac-
torial, in newborns and small infants ARF is nearly al-
ways secondary to ischemia and hypoxia of kidneys
caused by other organ failure [14]. Following the isch-
emic injury, renal function and kidney histology undergo
progressive deterioration over a period ranging from 48
to 72 hours. If the individual survives, a progressive re-
covery process is initiated, resulting in total or partial
restitution of the renal function, depending on the severi-
ty of the tissue lesion, on associated factors (malnutri-
tion, nephrotoxic drugs, hemodynamic situation, etc.),
and on the available therapeutic measures [15, 16, 17].
Over the last few years, several lines of investigation
have been developed to find a suitable therapeutic agent,
which should promote cellular growth and differentia-
tion, improve renal hemodynamics, reduce inflamma-
tion, and maintain vascular integrity [18]. To this end,
diuretics, dopamine, atrial natriuretic factor, calcium
channel antagonists, and growth factors have been tested
A. Medina · F. Santos (
✉
) · B. Amil · J. Rodríguez · M. Crespo
Department of Pediatrics, Hospital Central de Asturias,
SESPA, Asturias, Spain
e-mail: fsantos@correo.uniovi.es
Tel.: +34-985103585
A. Medina · M. Fernández-Fuente · F. Santos · B. Amil
J. Rodríguez · M. Crespo
Department of Pediatrics, School of Medicine,
University of Oviedo, Oviedo, Asturias, Spain
E. Carbajo-Pérez
Department of Anatomy, School of Medicine,
University of Oviedo, Oviedo, Asturias, Spain
M. Fernández-Fuente · E. Carbajo-Pérez · F. Santos ·
J. Rodríguez · M. Crespo
Instituto Universitario de Oncologia del Principado de Asturias,
University of Oviedo, Oviedo, Asturias, Spain
F. Santos
Pediatría, Facultad de Medicina. C/Julián Clavería s/n,
33006 Oviedo, Asturias, Spain
Pediatr Nephrol (2002) 17:1005–1012
DOI 10.1007/s00467-002-0979-y
ORIGINAL ARTICLE
Alberto Medina · Marta Fernández-Fuente
Eduardo Carbajo-Pérez · Fernando Santos
Benito Amil · Julián Rodríguez · Manuel Crespo
Insulin-like growth factor I administration in young rats
with acute renal failure
Received: 18 April 2002 / Revised: 26 July 2002 / Accepted: 26 July 2002 / Published online: 14 November 2002
© IPNA 2002