Download Decrease in the haemoglobin level in haemodialysis patients

Nephrol Dial Transplant ( 1997) 12: 1262–1263
Nephrology
Dialysis
Transplantation
Case Report
Decrease in the haemoglobin level in haemodialysis patients undergoing
antiandrogen therapy
J. L. Teruel, T. Cano, R. Marcén, J. J. Villafruela, M. Rivera, G. Fernández-Juarez and J. Ortuño
Servicio de Nefrologı́a, Hospital Ramón y Cajal, Madrid, Spain
Key words: haemodialysis; antiandrogen therapy; leuprolide; haemoglobin
Introduction
There are several known haematopoietic growth factors and cytokines. Among them, erythropoietin is an
essential hormone for the regulation of red blood cell
production. Clinical evidence suggests that androgens
also play a role in erythropoiesis. Men and women
exhibit dierences in haemoglobin concentration and
during puberty, haemoglobin levels increase only in
males. Moreover, it has been shown that haemoglobin
levels decline after castration or antitestosterone
therapy [1–3]. Levels of erythropoietin are similar in
both men and women, and therefore it is assumed that
testosterone is responsible for the observed dierences
in haemoglobin levels.
Anaemia in uraemic patients is a consequence
of inappropriately low erythropoietin production.
Generally, it is most severe in women and children,
suggesting that erythropoiesis in end-stage renal failure
is also influenced by androgens [4]. A role for androgens in erythropoiesis is supported by the fact that
pharmacological doses of androgens have been used
to treat anaemia successfully. However, male end-stage
renal failure patients frequently have low testosterone
levels [5] and it remains to be determined whether
testosterone contributes to erythropoiesis in uraemic
male patients.
We observed a profound decrease in the haemoglobin levels of three male haemodialysis patients
undergoing antiandrogen therapy. This clinical observation supports the notion that even low levels of
testosterone may have a positive influence on erythropoiesis in chronic renal failure.
Correspondence and oprint requests to: Dr J. L. Teruel, Servicio de
Nefrologı́a, Hospital Ramón y Cajal, Carretera de Colmenar km
9.100, 28034 Madrid, Spain.
Case reports
Three Caucasian haemodialysis patients were diagnosed with prostatic cancer. The clinical and biochemical data at the time of diagnosis are shown in Table 1.
During the 12 months prior to diagnosis, stable haemoglobin levels were maintained with monthly doses of
62.5 mg of elemental iron in the form of sodium ferric
gluconate i.v. None of the patients was administered
human recombinant erythropoietin.
Prostatic carcinoma was treated with antiandrogen
therapy which consisted of a depot preparation of
leuprolide acetate (7.5 mg every 4 weeks by i.m. injection) and 250 mg flutamide t.i.d. Androgen blockade
was very eective; serum testosterone, luteinizing hormone, and prostate-specific antigen levels decreased in
all patients and reached undetectable levels after the
3rd month of antiandrogen treatment.
Figure 1 shows the haemoglobin levels 6 months
before, and after the initiation of antiandrogen treatment. Haemoglobin levels were decreased 1 month
post-treatment and the three patients required
recombinant human erythropoietin therapy to control
anaemia at 3, 4 and 5 months respectively postantiandrogen treatment. The patients remained
Table 1. Clinical and biochemical data at the time of diagnosis of
prostatic carcinoma
Aetiology of
renal disease
Months on
haemodialysis
Age
Prostate-specific
antigen (ng/ml )
(normal <4 )
Testosterone
(ng/ml )
(normal
range
3–11)
Prostatic
carcinoma
staging
© 1997 European Renal Association–European Dialysis and Transplant Association
Patient 1
( Polycystic
disease)
Patient 2
( Polycystic
disease)
Patient 3
( Interstitial
nephropathy)
24
29
130
48
16
69
24
79
31
1.5
D1
2.8
C1
2.1
C2
Decrease in haemoglobin level in haemodialysis patients on antiandrogen therapy
Fig. 1. Haemoglobin levels in three male haemodialysis patients
undergoing antiandrogen treatment. rHuEPO: Start of treatment
with recombinant human erythropoietin.
asymptomatic after 1 year of antiandrogen treatment
with a stable haemoglobin concentration. At this time
haemoglobin levels and the maintenance dose of intravenous recombinant erythropoietin were 9 g/dl and
152 IU/kg/week ( patient 1), 10.1 g/dl and 347
IU/kg/week (patient 2 ) and 9.8 g/dl and 384
IU/kg/week (patient 3 ) respectively. The serum
erythropoietin levels did not change during the first 3
months of antiandrogen therapy. The values immediately before and 3 months after treatment were 6 and
8 mlU/ml (patient 1 ), 10 and 14 mlU/ml (patient 2)
and 27 and 25 mlU/ml (patient 3 ) respectively.
1263
level. The combination of these two substances results
in total androgen blockade [7 ]. We observed a sharp
decline in the haemoglobin levels of the three male
haemodialysis patients with prostatic carcinoma who
were treated with these two drugs. A mild, but statistically significant decrease in haemoglobin was also
observed in male patients with normal renal function
treated with a similar androgen blockade regimen [3 ].
Before antiandrogen therapy, the haemoglobin levels
of all three patients with hypogonadism were maintained with intravenous iron supplementation. One
month following testosterone blockade, there was a
profound decline in haemoglobin concentration not
associated with changes in erythropoietin levels. This
fall in haemoglobin concentrations cannot be attributed to malignancy since it coincided with the initiation
of antiandrogen therapy and did not improve with the
decrease in prostatic specific antigen concentration.
Our data suggest that the low testosterone levels in
these patients were necessary to maintain haemoglobin
concentrations through a mechanism independent of
the erythropoietin level. Therefore, testosterone
appears to be involved in the regulation of erythropoiesis in male patients with chronic renal failure. The
mechanism of action of androgenic steroids may be an
increase in the sensitivity of erythroid progenitors to
erythropoietin.
Acknowledgements. This work was supported in part by Grant
Number 1303 from Fundación LAIR.
References
Discussion
The influence of testosterone on erythropoiesis in
humans with normal renal function may account for
the dierences in haemoglobin concentrations observed
between healthy women and men and explain the
decline in haemoglobin levels seen after androgen
blockade. Chronic renal failure patients commonly
suer from anaemia secondary to erythropoietin deficit. The possible eects of other growth factors such
as androgen steroids on erythropoiesis in end-stage
renal failure have not been extensively studied. Many
male patients with end-stage renal disease have hypogonadism and low levels of testosterone and it is
unclear how this aects the regulation of erythropoiesis. However, it has been shown that exogenous
androgens potentiate the eects of recombinant
erythropoeitin in uraemic patients [6 ].
Leuprolide is an analogue of luteinizing hormonereleasing factor and flutamide is a synthetic antiandrogen drug competing with androgens at the receptor
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Received for publication: 26.7.96
Accepted in revised form: 22.1.97