Nephrology Dialysis Transplantation, Vol 13, Issue 9 2210-2215, Copyright © 1998 by Oxford University Press
V Bellizzi, M Sabbatini, G Fuiano, G Sansone, P Magri, F Uccello, M Andreucci, L De Nicola and B Cianciaruso
Background: Correction of anaemia in moderate to
advanced renal failure is still a matter of debate because of postulated
detrimental effects of erythropoietin on the progression of renal damage.
Methods: The renal effects of early normalization of
haematocrit (Htc) by erythropoietin (rHuEpo) were investigated from the
time of 5/6 nephrectomy up to 8 weeks post-intervention in three groups of
remnant kidney model rats: untreated controls (CON), rats receiving 100
UI/kg body-wt of rHuEpo i.p. twice a week (EPO), and rats receiving rHuEpo
in which periodic phlebotomies maintained Htc similar to the value of the
control group (PHL). The latter group was included to evaluate the direct
effects of rHuEpo on renal damage, i.e. independent from Htc correction.
Results: Two weeks after renal ablation (basal), Htc
decreased in CON and PHL (from 49.3±1.4% to 43.2±1.1,
P<0.05 and from 49.6±1.1 to 43.3±1.5%
P<0.05 respectively), while it remained consistently normal in EPO
rats (78.9±1.2% to 48.8±1.5%, P<0.05
vs other groups). Thereafter Htc did not change
throughout the remaining period in all groups. At the end of the study,
with respect to basal, resting blood pressure increased significantly by
the same extent in CON (+13±2%) and EPO rats
(+15±5%), while it remained constant in PHL rats. Notably,
creatinine clearance significantly decreased in CON (-53±8%
vs basal) and EPO (-38±8%
vs basal), while it did not change in PHL rats.
Likewise the degree of proteinuria as well as renal morphologic alterations
and glomerular hypertrophy/sclerosis was similar in CON and EPO rats, and
was significantly more severe than in the phlebotomized group. The only
difference detected between CON and EPO group was the greater mesangial
hypercellularity in rHuEpo-treated rats. Conclusion:
In uraemic rats, chronic treatment with rHuEpo aimed at normalization of
Htc beginning the early stage of renal failure does not inevitably account
for a rise in systemic blood pressure. In addition, neither erythropoietin
per se nor the correction of haematocrit accelerates
the progression of renal damage when blood pressure remains constant.
Key words: erythropoietin; haematocrit; morphometry;
progression of renal failure; proteinuria; remnant kidney model rats
ORIGINAL ARTICLES
The impact of early normalization of haematocrit by erythropoietin on renal damage in the remnant kidney model
Divisions of Nephrology, School of Medicine, University of Naples 'Federico II', C. so Europa, 26, I-80127 Napoli, Italy; University of Catanzaro, Italy; Corresponding author
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