Causes of Anemia in Renal Transplant Recipients

S. Karakus, M. Kanbay, H. Kart Koseoglu, T. Colak, and M. Haberal

ABSTRACT
Iron-deficiency anemia is one of the major problems encountered in renal transplant
recipients. The aim of this retrospective study was to reevaluate the causes of anemia
among 100 anemic kidney recipients. Patients with serum creatinine levels greater than 2
mg/dL were excluded from the study. Female patients were considered to be anemic if the
hemoglobin was 12 g/dL for males, 13 g/dL. Complete blood count, serum creatinine,
serum iron, iron-binding capacity, ferritin, transferrin saturation, erythrocyte folate, and
serum vitamin B12 levels were measured in all patients. Mean hemoglobin value was 10.2
1.4 g/dL for female and 9.9 1.3 for male patients, mean corpuscular volume (MCV)
91.3 4.9 fL. We observed normocytic anemia in 60, macrocytic anemia in 30, and
microcytic anemia in 10 patients. A low level of serum folate was observed in 9 (15%) and
of vitamin B12 in 5 (8.8%) of 60 patients with normocytic anemia. Folate deficiency was
found in 18 (60%) and vitamin B12 deficiency in 12 (40%) of 30 patients with macrocytic
anemia. All patients with microcytic anemia had iron deficiency. Splenomegaly was seen
significantly more often in patients with macrocytic than normocytic anemia (P .008).
Folate and vitamin B12 deficiency were the major causes of nutritional anemia; oral or
parenteral supplementation with these vitamins is likely to cure the anemia in the majority
of cases.

NEMIA IS A COMMON complication of chronic

renal failure. There are numerous causes of anemia
in this patient group, the most important of which is
decreased production of erythropoietin by the kidney. In
cases of anemia due to erythropoietin deficiency, improvement is usually observed 3 to 6 months after renal transplantation.1,2 However, other etiologic factors, such as
acute or chronic graft rejection, nutritional deficiencies,
chronic infection, immunosuppressive drugs (azathioprine,
tacrolimus, cyclosporine), and antibiotics such as trimethoprim, can all play roles in the development of anemia
after renal transplantation.35 Our aim was to investigate
the causes of anemia in renal transplant recipients at our
center.

definitive causes of anemia. Female patients were considered to be

anemic if serum hemoglobin measured 12 g/dL, and the corresponding level for males was 13 g/dL. Each patient underwent
measurements of a complete blood count, serum creatinine, serum
iron, serum ferritin, iron-binding capacity, transferrin saturation
level, erythrocyte folate concentration, serum vitamin B12 level,
hepatitis B surface antigen, and antibodies to hepatitis C virus. All
patients had upper gastrointestinal endoscopy and abdominal
ultrasonography. Relation of anemia to an endoscopic lesion of
organomegaly were also evaluated. Patients with spleen length
above 130 mm by ultrasonography were diagnosed to have splenomegaly.

RESULTS

MATERIALS AND METHODS

Table 1 summarizes patient demographic characteristics

and the values for different parameters. The mean hemoglobin value in the women was 10.2 1.4 g/dL and that for

The study involved 100 anemic kidney recipients (37 women and 63
men) who underwent renal transplantation between January 1,
1995, and December 31, 2002. The group included patients with
anemia that persisted at least 6 months after renal transplantation,
as well as patients who developed anemia after surgery. Patients
with serum creatinine levels above 2 mg/dL were excluded from the
study.
The medical records were retrospectively assessed for possible or

From the Division of Hematology (S.K.), Department of Internal

Medicine (M.K.), Division of Rheumatology (H.K.K.), Division of
Nephrology (T.C.), and Department of General Surgery (M.H.),
Baskent University Hospital, Ankara, Turkey.
Address reprint requests to Sema Karakus, MD, Baskent
University Division of Hematology 12.sok 7/5, Bahcelievler Ankara 06490, Turkey. E-mail: sema_karakus@hotmail.com

0041-1345/04/$see front matter

doi:10.1016/j.transproceed.2003.11.005
164

2004 by Elsevier Inc. All rights reserved.

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Transplantation Proceedings, 36, 164165 (2004)

ANEMIA IN RENAL TRANSPLANT RECIPIENTS

Table 1. Demographic, Clinical, and Laboratory Parameters
That Were Reevaluated in the 100 Renal Transplant Recipients
With Anemia
Sex (male/female)
63/37
Age (years male/female)
35.4 12.3/35.3 10.2
Hemoglobin (g/dL; male/female)
9.9 1.3/10.2 1.4
Type of anemia
Normocytic (MCV 80 95 fL)
60
Macrocytic (MCV 95 fL)
30
Microcyctic (MCV 80 fL)
10
Upper gastrointestinal endoscopy findings
Normal
19
Atrophic gastritis
5
Erosive gastritis
45
Peptic or duodenal ulcer
10
Bulbitis
21
Helicobacter pylori positivity
11
Anti-hepatitis C virus antibody positivity
18
Hepatitis B virus surface antigen positivity
1
MCV: mean corpuscular volume.

men was 9.9 1.3 g/dL. The mean value for mean
corpuscular volume (MCV) was 91.3 4.9 fL. Sixty patients
(60%) had normocytic anemia (MCV 80 to 95 fL) 30
(30%) had macrocytic anemia (MCV 95 fL), and 10
(10%) had microcytic anemia (MCV 80 fL). Among the
60 patients with normocytic anemia, 9 (15%) had belownormal serum folate levels and 5 (8.3%) below-normal
vitamin B12 levels. Of the 30 patients with macrocytic
anemia, 18 (60%) exhibited folate deficiency and 12 (40%)
vitamin B12 deficiency. All 10 patients with microcytic
anemia were suffering from iron deficiency. Abdominal
ultrasonography revealed splenomegaly in 21 transplant
patients. The frequency of splenomegaly was significantly
higher among patients with macrocytic anemia (30%) than
those with normocytic anemia (11.7%) (P .008). All 100
patients had been given corticosteroids. In addition, 56
patients had received cyclosporine, 23 had received cyclosporine plus azathioprine, six had received mycophenolate
mofetil, 11 had received mycophenolate mofetil plus tacrolimus, and four had received various combinations of
these drugs.
All patients had undergone upper gastrointestinal endoscopy. Forty-five of them were diagnosed with erosive gastritis, 10 with duodenal ulcer, 21 with bulbitis, five with
atrophic gastritis, and the remaining 19 had normal endoscopy findings. Urcase testing for Helicobacter pylori was
positive in only 11 patients. All patients had received
H2-receptor blockers and some had also taken proton pump
inhibitors after renal transplantation. Concerning serologic
findings, 18 patients were positive for anti-hepatitis C virus
antibody and 1 for hepatitis B virus surface antigen.

165

DISCUSSION

Iron-deficiency anemia is generally believed to be the major

problem4,6; however, the results of this study show that this
was not the case in our unit. The reason for this is likely the
multiple red cell transfusions that our patients receive to
correct hematocrit levels. It is noteworthy that the frequency of iron-deficiency anemia was low in our study
group, even though we observed a high incidence of upper
gastrointestinal lesions. The rate of H pylori infection was
low, all patients had been on H2-receptor blockers, and
some had received proton pump inhibitors. These factors
may explain why such high-risk patients did not suffer
chronic iron loss.
Mycophenolate mofetil and azathioprine have been reported to induce erythropoietin production and resistance
in renal transplant recipients.7 We found no correlation
between the immunosuppressive drug regimen and anemia
in our study. As mentioned, research has shown that most
patients with anemia due to erythropoietin deficiency improve within 3 to 6 months after successful kidney transplantation. One limitation of our study was that it was
retrospective, and erythropoietin levels were not measured.
Folate and vitamin B12 deficiency were the major causes
of anemia in our series. This nutritional anemia is a result
of poor dietary intake before and after renal transplantation. It is also of note that the frequency of splenomegaly
was significantly higher among patients with macrocytic
anemia than the other two anemia groups. The group with
splenomegaly displayed a significantly higher frequency of
hepatitis C virus infection than the group without splenomegaly. These findings may be at least partially explained by
impaired folic acid and vitamin B12 metabolism in chronic
hepatitis C virus-related liver disease. Oral or parenteral
supplementation of these vitamins may cure anemia in most
of the cases.
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