American Journal of Transplantation 2007; 7: 818–824
Blackwell Munksgaard
C 2007 The Authors
C 2007 The American Society of
Journal compilation Transplantation and the American Society of Transplant Surgeons
doi: 10.1111/j.1600-6143.2006.01727.x
Anemia Is Associated with Mortality
in Kidney-Transplanted Patients—A Prospective
Cohort Study
M. Z. Molnara,b,c , M. Cziraa , C. Ambrusb,c ,
L. Szeiferta , A. Szentkiralyia , G. Bekod ,
L. Rosivalle , A. Remportf , M. Novaka,g
and I. Mucsia,b,e,∗
Received 2 October 2006, revised 4 December 2006 and
accepted for publication 21 December 2006
Introduction
a
Institute of Behavioral Sciences, Semmelweis
University, Budapest, Hungary, b 1st Department
of Internal Medicine, Semmelweis University, Budapest,
Hungary, c Semmelweis University—Fresenius Medical
Care Dialysis Center, Budapest, Hungary, d Central
Laboratory, Semmelweis University, Budapest, Hungary,
e
Hungarian Academy of Sciences and Semmelweis
University Nephrology Research Group, Budapest,
Hungary and f Department of Transplantation and Surgery,
Semmelweis University, Budapest, Hungary
g
Department of Psychiatry, University Health Network,
University of Toronto, Toronto, Canada
*Corresponding author: Istvan, Mucsi
[email protected]
Although anemia is a known risk factor of mortality
in several patient populations, no prospective study
to date has demonstrated association between anemia and mortality in kidney-transplanted patients. In
our prospective cohort study (TransQol-HU Study), we
tested the hypothesis that anemia is associated with
mortality and graft failure (return to dialysis) in transplanted patients. Data from 938 transplanted patients,
followed at a single outpatient transplant center, were
analyzed. Sociodemographic parameters, laboratory
data, medical history and information on comorbidity were collected at baseline. Data on 4-year outcome (graft failure, mortality or combination of both)
were collected prospectively from the patients’ charts.
Both mortality and graft failure rate during the 4year follow-up was significantly higher in patients who
were anemic at baseline (for anemic vs nonanemic patients, respectively: mortality 18% vs. 10%; p < 0.001;
graft failure 17% vs 6%; p < 0.001). In multivariate Cox
proportional hazard models the presence of anemia
significantly predicted mortality (HR = 1.690; 95% CI:
1.115–2.560) and also graft failure (HR = 2.465; 95% CI:
1.485–4.090) after adjustment for several covariables.
Anemia, which is a treatable complication, is significantly and independently associated with mortality
and graft failure in kidney-transplanted patients.
Key words: Anemia, chronic renal disease, kidney,
mortality, transplantation outcomes
818
The pathogenesis of posttransplant anemia (PTA) is multifactorial, but declining renal function and failing erythropoietin synthesis plays an important role (1). Although the
reported prevalence of PTA shows great variations in different studies (2–6), the three recent surveys enrolling
the largest number of patients reported a more consistent prevalence of 30–40% (2,3,6). Severe anemia, requiring treatment based on current guidelines, is less frequent
with an estimated prevalence of about 10–15% (2,6).
Recent studies have demonstrated an association between lower hemoglobin levels and mortality both in dialysis (7,8) and in chronic kidney disease (CKD) patients
not yet on dialysis (9). However, conflicting results have
been published on the association between anemia and
outcome in kidney-transplanted patients. In a prospective
study, Winkelmayer at al. found no significant association
between anemia or serum hemoglobin level versus outcome (mortality or graft failure) (10). On the other hand,
in a retrospective analysis, Heinze et al. suggested that
anemia may be associated with mortality in the kidneytransplanted patients (11).
Similar to dialyzed patients, cardiovascular diseases are
the leading cause of death in the kidney-transplanted
population (12,13). Anemia is associated with early posttransplant cardiovascular risk in diabetic patients (14).
Furthermore, the presence of anemia is an independent
predictor of both left ventricular hypertrophy (15) and congestive heart failure (16) in transplanted patients. It has
also been reported that both left ventricular hypertrophy
and congestive heart failure were independent predictors
of mortality in this population (15,16). It is, therefore, conceivable that the presence of anemia is a predictor of negative outcome in transplanted patients.
In addition to potentially leading to cardiovascular disease,
anemia may also contribute to more rapid loss of renal
function in patients with impaired renal function (17). A
recent study suggested that anemia significantly predicted
the decline of renal function among CKD patients (9) and
Anemia and Mortality in Transplanted Patients
also among heart-transplant recipients (18). Furthermore,
Gouva et al. have recently shown that treating anemia in
CKD patients can slow the decline of renal function (19).
On the basis of the above information, we hypothesized
that PTA is associated with negative outcome, i.e. with
mortality and graft failure (return to dialysis) in kidneytransplanted patients. To test this hypothesis, a prospective cohort study was designed. More than 900 kidneytransplanted patients were followed at a single transplant
clinic for about 46 months and data on outcome were
collected prospectively. Our results revealed that the presence of anemia is independently and significantly associated with both mortality and graft failure in kidneytransplanted patients.
Materials and Methods
Sample of patients and data collection
All patients 18 years of age or older (n = 1067) who were regularly followed
at a single kidney transplant outpatient clinic at the Department of Transplantation and Surgery at the Semmelweis University, Budapest, were invited
to participate in a prospective cohort study. The baseline assessment was
conducted between August 2002 and February 2003 (Transplantation and
Quality of Life-Hungary Study (TransQoL-HU Study)). Of the 1067 eligible
patients, 108 (10%) refused to participate in the study and 21 (2%) patients
were lost during follow up. The study population, therefore, included 938
patients.
Demographic data and details of medical history were collected at enrollment when information about age, gender, etiology of CKD, the presence
or absence of diabetes, hypertension and other comorbidities were obtained. Laboratory data were extracted from the patients’ charts and from
the electronic laboratory database of the hospital. The following laboratory
parameters were tabulated: serum hemoglobin (Hb), transferrin saturation
(TSAT), C-reactive protein, serum creatinine, blood urea nitrogen (BUN) and
serum albumin. Transplant-related data extracted from the medical records
included the following information: medications (including current immunosuppressive treatment), transplant ’vintage’, i.e. time elapsed since the time
of the transplantation. Estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease (MDRD)
study formula (20):
eGFR(mL/min per1.73m2 )
= 186 × (SCr)−1.154 × (Age)−0.203 (×0.742 if female)
The study was approved by the Ethics Committee of the Semmelweis University. Before enrolment, the patients received detailed written and verbal
information regarding the aims and protocol of the study.
Follow-up
From the day of the baseline visit, patients were followed up for about
4 years (median, [interquartile range, IQR]: 46, [6] months). Data related
to three predefined outcomes were collected during follow-up. These outcome variables were: 1, death (mortality); 2, graft failure, i.e. returning to
dialysis; 3, combined outcome: death or returning to dialysis. The occurrence and date of death or reinitiation of maintenance dialysis due to graft
failure was recorded in our electronic database. The cause of death was
extracted from the charts.
Definition of anemia
Similar to previous publications, anemia was defined according to the anemia guideline of the American Society of Transplantation: hemoglobin under
American Journal of Transplantation 2007; 7: 818–824
130 g/L in adult males, and 120 g/L in adult females (21). In addition to the
above definition, we also reanalyzed our data using a cut-off value of serum
hemoglobin lower than 110 g/L that is suggested to trigger treatment with
erythropoiesis stimulating agents (ESAs) in patients with CKD, including
kidney-transplanted patients, by the NKF-K/DOQI guideline (22) and the European Best Practice guideline (23,24). Similar definition was also used by
Winkelmayer et al. in their recent analysis (25).
Self-reported comorbidity
Information on the presence or absence of comorbid conditions was obtained from the patients. Patients were asked at enrollment if they suffered
from conditions (heart disease, vascular disease, bone, lung or eye disorders, neuropathy, diabetes mellitus or other, not-defined conditions) that
are assessed by the Endstage Renal Disease Severity Index (ESRD-SI) (26).
Self-reported comorbidity score was calculated by summing up the number of comorbid conditions the patients reported. Earlier work of our group
suggested that this score provides valuable information and it correlates
with the overall clinical condition of the patients (6,27,28). Patients were
also asked at enrolment if they suffered from hypertension or not.
Immunosuppressive therapy
Standard immunosuppressive therapy generally consisted of prednisolone,
either cyclosporine A (Neoral) (CsA) or tacrolimus, combined with mycophenolate mofetil (MMF) or azathioprine or rapamycine.
Statistical analysis
Statistical analysis was carried out using the SPSS 10.0 software. Continuous variables were compared using Student’s t-test or the Mann-Whitney
U test and categorical variables were analyzed with the chi-square test.
To assess variables associated with the outcome measures, univariate and
multivariate Cox proportional hazards analyses and Kaplan-Meier survival
plots were used.
Results
Demographics and baseline characteristics
of the sample
Of the 1067 eligible patients, 108 refused to participate in
the study and 21 additional patients were lost during the
follow-up period. The study population, therefore, included
938 patients. The mean age was 49 ± 13 years, 59% were
males and 17% were diabetics (Table 1). Mean estimated
eGFR was 49 ± 22 mL/min/1.73 m2 , mean serum albumin
was 42 ± 3 g/L, the prevalence of iron deficiency was 11%.
The median time since transplantation at enrollment was
55 months (Table 1).
The most prevalent underlying kidney disease in the sample was chronic glomerulonephritis (18%). The prevalence of other kidney diseases were: diabetic nephropathy
14%; autosomal dominant polycystic kidney disease 12%;
chronic pyelonephritis and tubular interstitial disease 11%;
hypertensive nephropathy 8%. Other or unknown underlying kidney disease accounted for 37%. Nine percent of the
study population has had one or more previous transplants.
At the time of enrolment almost 90% of the patients (823
patients, 88%) were taking prednisolone and more than
two-thirds (657 patients, 70%) were on cyclosporine A
therapy. The number of patients taking MMF was 585
819
Molnar et al.
Table 1: Patients characteristics
Presence of anemia
(n = 317)
Absence of anemia
(n = 621)
p-Value
59
49 ± 13
17
55; 63
57
48 ± 13
18
56; 73
60
49 ± 12
16
54; 58
NS
NS
NS
NS
23; 29
23; 28
23; 30
NS
49 ± 22
2 (0–7)
42 ± 3
3; 6
25 ± 4
8
17
118 (13%)
79 (10%)
197 (21%)
43 ± 20
2 (0–7)
41 ± 3
4; 7
25 ± 5
20
14
58 (18%)
44 (17%)
102 (32%)
53 ± 22
2 (0–7)
42 ± 3
2; 5
25 ± 4
3
19
60 (10%)
35 (6%)
95 (15%)
<0.001
NS
<0.001
0.001
NS
<0.001
NS
<0.001
<0.001
<0.001
(62%). Somewhat more than 10% of the patients were
taking tacrolimus (160 patients, 17%) or azathioprine (117
patients, 12%), respectively. Twenty patients (2%) were
given sirolimus. Only 63 (20%) anemic patients were on
erythropoietin therapy. Only 151 (17%) patients were taking angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) and 704 (82%) patients
were taking any antihypertensive medications.
Anemic patients had significantly lower eGFR and serum
albumin levels than nonanemic individuals had (Table 1).
The serum CRP and the proportion of patients receiving
erythropoietin were higher in patients with anemia than in
the group without this disorder (Table 1).
The cohort was followed-up for a period of about 4 years
(median 46 months). Over 3188 person-years, 118 patients
died (crude mortality rate = 37/1000 person-years), and
over 2998 person-years 79 patients returned to dialysis
(crude rate of graft failure = 26/1000 person-years). During
the follow-up, 23% of patients died from cardiovascular
complications, 18% died from malignant disorders, 30%
of the deaths were related to infectious complications and
29% of the patients died from other or unknown causes.
Univariate analysis of predictors of mortality, graft
failure and the combined outcome
All three outcome measures were significantly more frequent in the initially anemic group than among nonanemic
patients (mortality: 18% vs. 10%; p < 0.001; return to dialysis: 17% vs. 6%; p < 0.001; combined outcome: 32%
vs. 15%; p < 0.001) (Table 1). Patients without anemia had
significantly better survival than those with anemia, as it is
clearly demonstrated by the Kaplan-Meier plot (Figure 1).
Similar association was found for graft failure, as well
(Figure 2).
820
To identify variables significantly associated with negative
outcome, univariate Cox proportional hazard analyses were
performed. A significant association was found between
serum hemoglobin and mortality (HR for each 1g/L decrease =
1.016; 95% CI: 1.007–1.025), and also between anemia
and mortality (HR = 2.092; 95% CI: 1.458–3.003) (Table 2).
In these analyses age, male gender, lower eGFR, lower
serum albumin, higher serum C-reactive protein (CRP)
level, comorbidity, presence of diabetes mellitus, presence
of hypertension, pretransplant time on dialysis and transplantation ‘vintage’ were also associated with mortality
(Table 2). We did not find any association between mortality
1,0
: non anemic
: anemic
,9
Cumulative Survival
Male (%)
Age (years) (mean ± SD)
Diabetes mellitus (%)
Transplantation vintage (months)
(median; interquartile range (IQR))
Pretransplant time on dialysis (months)
(median; interquartile range (IQR))
eGFR (mL/min/1.73 m2 ) (mean ± SD)
Number of comorbid conditions (median; (min.–max.))
Serum albumin (g/L) (mean ± SD)
CRP (mg/L) (median; interquartile range)
Body mass index (kg/m2 ) (mean ± SD)
Erythropoietin therapy (%)
ACEI or ARB medications (%)
Mortality (n (%))
Return to dialysis (n (%))
Combined outcome (n (%))
Total population
(n = 938)
,8
,7
0
10
20
30
40
50
Follow-up time (months)
Log Rank: p<0.0001
Figure 1: Presence of anemia at enrollment and survival
(Kaplan-Meier plot).
American Journal of Transplantation 2007; 7: 818–824
Anemia and Mortality in Transplanted Patients
1,0
tion of ACEI or ARB or different immunosuppressive drugs
(data not shown).
: non anemic
: anemic
Similar results were seen for the combined outcome as
well (Table 2).
Cumulative Graft Survival
,9
,8
,7
0
10
20
30
40
50
Follow-up time (months)
Log Rank: p<0.0001
Figure 2: Presence of anemia at enrollment and return to dialysis (Kaplan-Meier plot).
and the administration of ACEI or ARB or the different immunosuppressive drugs (not shown).
In a similar set of analyses, both serum hemoglobin
(HR foreach1g/Ldecrease = 1.027; 95% CI: 1.016–1.038) and the
presence of anemia (HR = 2.934; 95% CI: 1.882–4.574)
were significantly associated with reinitiation of maintenance dialysis (Table 2). The univariate analyses also identified age, presence of diabetes mellitus, pretransplant time
on dialysis, lower eGFR and lower serum albumin level as
significant predictors of graft failure (Table 2). No association was found between graft failure and the administra-
Multivariate analyses
To assess the independent association of anemia and negative outcome, multivariate models were built. All variables
that showed significant association with the outcome measures in the univariate Cox models were considered for inclusion in the multivariate models. Accordingly, age, gender, eGFR, serum albumin, CRP, comorbidity (that included
diabetes), pretransplant time on dialysis, transplantation
‘vintage’ and the presence of hypertension were the covariables entered into the multivariate Cox proportional hazards models in addition to the presence of anemia. On the
basis of these models, it was found that the presence of
anemia is significantly and independently associated with
both mortality (HR = 1.690; 95% CI: 1.115–2.560) and also
with graft failure (HR = 2.465; 95% CI: 1.485–4.090) in
kidney-transplanted patients. Anemia was also significantly
associated with the combined outcome (HR = 1.969; 95%
CI: 1.432–2.707) (Table 3).
Serum hemoglobin was also significantly associated with
mortality (HR for each 1g/L decrease = 1.011; 95% CI: 1.001–
1.022) and graft failure (HR for each 1g/L decrease = 1.019; 95%
CI: 1.006–1.032) and with the combined outcome
(HR for each 1g/L decrease = 1.015; 95% CI: 1.007–1.023) in similar models (Table 3).
A similar model, using the cut-off value of serum
hemoglobin (Hb) below 110 g/L, was also tested. Age, gender, eGFR, serum albumin, CRP, comorbidity (that included
Table 2: Factors associated with negative outcome in kidney-transplanted patients—univariate ‘Cox proportional hazard’ analysis
Mortality
Hb (1 g/L decrease)
Presence of anemia
Age (1 year increase)
Gender (male)
Diabetes (presence)
eGFR (1 mL/min decrease)
BMI (1 kg/m2 increase)
Albumin (1 g/L decrease)
Number of comorbid conditions
(1 more illness)
Pretransplant time on dialysis
(1 month increase)
Transplantation vintage
(1 month increase)
Hypertension (presence)
CRP (1 mg/L increase)
Iron deficiency (TSAT <20%)
(presence)
Return to dialysis
Combined outcome
HR
95% CI
p-Value
HR
95% CI
p-Value
HR
95% CI
p-Value
1.016
2.092
1.044
1.552
3.087
1.027
1.001
1.143
1.183
1.007–1.025
1.458–3.003
1.027–1.061
1.052–2.289
2.063–4.618
1.016–1.038
0.958–1.046
1.092–1.197
1.065–1.315
0.001
<0.001
<0.001
0.027
<0.001
<0.001
0.967
<0.001
0.002
1.027
2.934
0.981
0.928
1.890
1.022
0.975
1.074
1.084
1.016–1.038
1.882–4.574
0.967–0.997
0.595–1.446
1.081–3.306
1.008–1.035
0.923–1.030
1.008–1.145
0.949–1.238
<0.001
<0.001
0.024
0.740
0.026
0.001
0.365
0.028
0.234
1.020
2.348
1.014
1.235
2.482
1.024
0.991
1.114
1.139
1.013–1.027
1.775–3.105
1.002–1.026
0.924–1.650
1.795–3.432
1.016–1.033
0.957–1.025
1.073–1.156
1.048–1.237
<0.001
<0.001
0.019
0.154
<0.001
<0.001
0.588
<0.001
0.002
1.008
1.003–1.012
<0.001
1.008
1.003–1.014
0.003
1.008
1.004–1.011
<0.001
1.004
1.001–1.008
0.017
1.003
0.998–1.008
0.193
1.004
1.001–1.006
0.009
1.615
1.007
1.304
1.054–2.473
1.002–1.012
0.670–2.538
0.028
0.008
0.434
1.402
1.002
0.514
0.848–2.318
0.991–1.014
0.160–1.649
0.188
0.698
0.263
1.502
1.006
0.954
1.085–2.079
1.001–1.011
0.538–1.693
0.014
0.022
0.872
American Journal of Transplantation 2007; 7: 818–824
821
Molnar et al.
Table 3: Multivariate “Cox proportional hazard” analysis
Mortality
Hb (1 g/L decrease)
Presence of anemia
Return to dialysis
Combined outcome
HR
95% CI
p value
HR
95% CI
p value
HR
95% CI
p value
1.011
1.690
1.001–1.022
1.115–2.560
0.033
0.013
1.019
2.465
1.006–1.032
1.485–4.090
0.003
<0.001
1.015
1.969
1.007–1.023
1.432–2.707
<0.001
<0.001
Adjusted for age, gender, eGFR, serum albumin, serum CRP, transplantation “vintage”, pretransplant time on dialysis, number of
comorbid conditions, presence of hypertension.
diabetes), pretransplant time on dialysis, transplantation
‘vintage’ and the presence of hypertension were the covariables entered into the multivariate Cox proportional hazards models in addition to the presence of serum Hb below 110 g/L. The presence of Hb level lower than 110 g/L
was significantly associated with both mortality and graft
failure.
Discussion
In this study we demonstrated that the presence of anemia is associated with survival and graft failure in kidneytransplanted patients. After controlling for several important covariables, patients with anemia had 1.69 times
higher chance to die within 4 years than patients without anemia. Furthermore, after adjustment for covariables,
anemic patients had a 2.46 times higher chance to return
to dialysis during the same follow-up period than patients
with higher Hb levels. These results from a large prospective cohort study confirm and extend the recent findings of
Heinze et al., who found significant association between
mortality and serum hemoglobin level in their retrospective
analysis (11).
In univariate analyses, serum Hb level was significantly
associated with survival after 46 months of follow-up.
After adjusting for several covariables in multivariate analyses, the association between serum Hb and mortality remained significant. Recently, Winkelmayer et al. did not
find significant association between mortality and serum
Hb. Those authors defined anemia as hemoglobin <100 g/L
(10), and this resulted in few events and insufficient statistical power.
Multiple potential mechanisms can explain the association
between anemia and mortality. Similarly to the CKD population, cardiovascular factors are the leading causes of
death also in kidney-transplanted patients (12,13,29). Anemia leads to hyperkinetic circulation, thicker left ventricular wall and congestive heart failure in kidney-transplanted
patients (15,16). These factors, in turn, are independent predictors of mortality in the transplant population (15,16). Anemia could also be the consequence of
malnutrition-inflammation complex syndrome (MICS), as
MICS was associated with erythropoietin hyporesponsiveness in dialysis patients (30). MICS, on the other
hand, is associated with mortality in dialysis patients (31).
822
Studies that aim to analyze this proposed association
in kidney transplant patients have been started by our
group.
Our results suggest that serum Hb or the presence of anemia is significantly and independently associated with graft
failure. After controlling for clinical variables, each 1 g/L
decrement in the level of serum hemoglobin increased
the odds of graft failure by 1.9% during the 46 months
follow-up period. An association between anemia and progression of renal failure has been suggested by previous
reports for CKD patients not yet on dialysis (9). Several
papers suggested that treating anemia can slow the decline of renal function in patients with chronic kidney failure (19,32,33). One potential link between anemia and decline of renal function could be the cardio-renal-anemia
syndrome that addresses the relationship between congestive heart failure, renal insufficiency and anemia (17).
Low serum hemoglobin reduces the oxygen-transport capacity of the blood, and it also contributes to left ventricular hypertrophy (15) and congestive heart failure (16). Congestive heart failure reduces the blood flow to the graft.
Thus the cardio-renal-anemia syndrome may link anemia
to graft failure through a complex mechanism that results
in hypoxia induced tubulointerstitial fibrosis and a decline
of graft function.
Recent studies have identified several risk factors that are
associated with mortality of kidney-transplanted patients.
Retrospective studies have shown that age, male gender
and smoking increases cardiovascular risk (34). In contrast
to findings in the general population, body mass index was
not associated with increased cardiovascular risk in kidneytransplanted patients (34). Our results are in accord with
these observations. Winkelmayer at al. recently reported
that the percentage ratio of hypochromic red blood cells,
a marker that is widely used to identify iron deficiency and
anemia of chronic disease, was an independent risk factor
of mortality in kidney-transplanted population (10). We did
not have information on the percentage of hypochromic
red blood cells; therefore, we had to rely on TSAT to assess iron deficiency. In our dataset, similar to the results of
Winkelmayer at al. (10), iron deficiency was not associated
with outcome. We obtained self-reported data about the
presence of hypertension. In this analysis, the presence
of self-reported hypertension was associated with mortality (Table 2). This association was no longer significant in
multivariate analysis (data not shown).
American Journal of Transplantation 2007; 7: 818–824
Anemia and Mortality in Transplanted Patients
Variable definitions of PTA are used in the literature (35).
We defined anemia according to the anemia guideline of
the American Society of Transplantation as hemoglobin under 130 g/L in adult males, and 120 g/L in adult females
(21). Similar definition was used in most previous epidemiological studies (2,3,6). To have a definition that could potentially affect patient care, we also used a cut-off value
of Hb lower than 110 g/L in our second set of multivariate
models. This definition reflects the lower limit of the target
range that should trigger treatment with ESAs in patients
with CKD according to the NKF-K/DOQI guidelines (22).
Several previous studies (25,36) also used this definition.
In this analysis the presence of anemia, defined by both of
these definitions, and in a different model also serum Hb as
a continuous variable was independently associated with
negative outcome, demonstrating a consistent and robust
association.
Our study is notable for enrolling the largest population in
question so far. An additional strength of the study is its
prospective design. In contrast to several earlier studies in
this field, important covariables (serum albumin, comorbidity including diabetes mellitus, immunosuppressive drugs)
were also used in the multivariate analyses. Correction for
these factors substantially increases the biological reliability of our model.
On the other hand, several limitations should be considered when interpreting our results. Information about
comorbid conditions was based on self report of the
patients. However, elements of the ESRD-SI, a valid comorbidity questionnaire (26) were integrated into our tool.
It is notable that the number of self-reported comorbid conditions was a strong predictor of mortality in our analysis. In
an earlier cross-sectional analysis the self-reported comorbidity score was also significantly correlated with several
domains of the SF-36 (quality of life) instrument in both
dialyzed and in kidney-transplanted patients. It was significantly correlated with serum albumin as well (37). Therefore, we suggest that this score provides valuable information about the overall clinical condition of the patients.
Another limitation of this study is that patients from a single
center were enrolled; therefore, our results are not to be
generalized without further considerations. Groups compared in cohort studies such as ours may have important differences that are unknown to the investigators
and this can potentially confound the results. Anemic patients in our study may have had more significant comorbid burden than nonanemic patients and that difference
may not have been fully accounted for in the multivariate
model. We did not have information on parameters (HLA
mismatch, panel reactive antibodies, cold ischemic time,
number of blood transfusion, acute rejection episodes, viral infections, smoking status, dyslipidaemia) that may be
associated with outcome. Additional risk factors, such as
microalbuminuria-proteinuria, left ventricular hypertrophy,
serum homocystein level, etc. were not measured either.
American Journal of Transplantation 2007; 7: 818–824
We cannot rule out the possibility that including all those
parameters, or other, yet unknown risk factors, would have
altered our results.
In summary, we found in this prospective cohort study
that the presence of anemia is independently and significantly associated with mortality and graft failure in kidneytransplanted patients even after controlling for several clinical variables. Together with earlier data, our result call for
a consideration of clinical trials to assess if treating PTA
can reduce mortality and improve graft survival in kidneytransplanted patients. Furthermore, the optimal target Hb
level for the patient population will have to be determined
in properly designed prospective studies.
Acknowledgments
The authors thank the patients and the staff in the Department of Transplantation and Surgery, Semmelweis University, Budapest, Hungary, for
helping this survey. We also thank Dr. E. Cole for critically reading the
manuscript. This study was supported by the NKFP 1/002/2001 project, the
National Research Fund (OTKA) projects nos: T-32974, TS-040889, T038409
(NM, MI), ETT 240/2000 and 218/2003) and TeT Foundation (2005/06, MN).
M.N. is recipient of the Hungarian Eotvos Scholarship. I.M. is a Bekesy
Scholar of the Hungarian Ministry of Education.
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