Recombinant human erythropoietin
(rHuEPO) has emerged as a new
renoprotective
agent against various
acute
kidney injuries. Experience
with
rHuEPO in chronic kidney injuries
is so far limited and conflicting
results
were obtained. In the present
study,
we addressed to evaluate the
long-term
renal effects of rHuEPO in
diabetic
nephropathy (DN) of rats in
relation
to novel hypoxia theory and
endogenous
EPO secretion. We
compared
rHuEPO to a standard
drug,
losartan (LSR), and the possibility
of add-on therapy was also
tested.
Thirty-four male SpragueDawley
rats were randomly divided
into
five groups: control-naïve group,
untreated
diabetic group, EPO- treated diabetic group (150 U/kg,
S.C., TIW), LSR-treated diabetic
group (5 mg/kg/day), and EPO-LSRtreated
diabetic group. Drug treatment
was started one week after
streptozotocin
(STZ) injection and
continued
for twenty-eight weeks.
STZ-treated
diabetic rats developed
progressive
albuminuria, renal dysfunction,
and significant glomerular
change
28 weeks after induction of
diabetes.
Chronic administration of
rHuEPO
alone or in combination with
LSR
to the STZ-induced diabetic rat
did
not show beneficial effect on DN
evolution,
inspite of improving diabetic-renal
hypoxia. The best beneficial
effect on DN evolution was obtained
by LSR sole therapy based on
renal
function evaluation, albuminu- ria, and renal histopathology. Interestingly,
administration of LSR either
alone
or in combination with rHuEPO
in
STZ-induced diabetic rats significantly
abolished increased plasma
endogenous
EPO. In conclusion, this
study
has questioned the renoprotective
role of low-dose rHuEPO in
the
setting of DN and confirmed that
this
low-dose rHuEPO used had adverse
effects on blood pressure and
increased
hematocrit level.