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| Year : 2011 | Volume
: 22
| Issue : 1 | Page : 104-106 |
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| Post transplantation anemia: Re-emphasizing the use of erythropoietin |
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Wael Latif Jabur
New Medical Center Specialty Hospital, Dubai, United Arab Emirates
Click here for correspondence address and email
| Date of Web Publication | 30-Dec-2010 |
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How to cite this article:
Jabur WL. Post transplantation anemia: Re-emphasizing the use of erythropoietin. Saudi J Kidney Dis Transpl 2011;22:104-6 |
 Introduction | |  |
One of the most common problems that are usually encountered post transplantation is anemia. [1] It is a widely recognized problem in most of the transplantation centers. The causes that invoke the anemia process in transplant patients are variable, and the morphology of anemia differs according to the underlying etiology. One of the frequently reported causes is the bone marrow suppression by the anti rejection therapies, mainly azathioprine and mycophenylate mofetil (MMF). [1] Other causes that might be responsible for the anemia in patients with normally functioning allograft include Parvo virus infection of the bone marrow, erythropoietin deficiency, bone marrow fibrosis secondary to long standing secondary hyperparathyroidism, and rarely, primary blood diseases. [2],[3],[4],[5],[6],[7],[8]
In this case report, the probable etiology and treatment potentials for anemia post renal transplantation are discussed.
| Case Report | | |
A 30-year-old patient, who was a renal allograft recipient, presented with a history of anemia of several years post transplantation. The primary cause of renal failure was unknown. There was no history of post transplant hypertension or diabetes mellitus. The donor was his sister and the HLA matching was 50%. Reviewing his medical records denoted an almost normal early post transplant period with prompt allograft function and no history of delayed function or slow graft recovery. Renal function was maintained within normal limits, and serum creatinine ranged between 1 and 1.2 mg/dL. He had neither a history of acute clinical rejection nor cyclosporine toxicity. He had not been monitored previously by programmed allograft biopsies. The anti-rejection regimen consisted of two pulses of methylprednisolone at the time of operation and 24 hours later, followed by tapered prednisolone dose, with the latest maintenance dose of 5 mg/day, in conjunction with cyclosporine neoral starting dose of 10 mg/kg body weight and serum cyclosporine C2 level of 1900 mg/L, gradually tapered over the past years to 483 mg/L in his later presentation and azathioprine 50 mg per day. He did not receive any medicine otherwise, except for tonics and iron supplements.
The patient's medical records showed that he was constantly anemic since early post transplantation time, but his anemia was not progressive and the serum iron profile repeatedly showed adequate iron storage. Examination was unremarkable, except for anemia. Investigations revealed hemoglobin (Hgb) concentration of 10.5 g/dL, oversaturated iron stores with serum ferritin of 850 mg/dL, transferrin saturation of 45%, normal C-reactive protein and erythrocyte sedimentation rate. Blood film showed normal morphology and pigmentation of red blood cells, and hemoglobin electrophoresis revealed normal pattern. Serum creatinine was 1.2 mg/dL and estimated glomerular filtration rate (eGFR) was 72 mL/min. Neither bone marrow biopsy nor screening for Parvo virus infection was performed. Serum erythropoietin hormone level was 13.9 IU/L (normal range 5.7-19.4 IU/L).
Treatment with erythropoietin 50 units/kg body weight per week was commenced as every other day subcutaneous injections. Regular follow-up of the patient for blood pressure, renal function test, Hgb, and body iron store profile was continued as an out-patient on weekly bases. After 1 month, his Hgb level was 12 g/dL, and renal function and blood pressure remained normal.
| Discussion | | |
Since the anemia in our patient dated back to early post transplant period, it might be related to pre-transplantation status of the bone marrow. Hyperparathyroidism might be immediately apparent in this period, but we could not point out any feature (investigational or radiological) highlighting the hyperparathyroidism. In addition, there was no evidence of pre-transplant hyperdynamic bone disease, and the detection of low serum erythropoietin level excluded bone marrow resistance.
The second cause that might be important is the Parvo B19 virus infection, which may lead to profound bone marrow suppression in transplantation recipients. [2] However, the non-progressive nature of our patient's anemia, and the low serum erythropoietin level were against this possibility.
Drug related anemia is commonly encountered post transplantation, especially for azathioprine, MMF, and sirolimus, [3] which might directly suppress all bone marrow cellular lines, but the red blood cells' morphology in this sort of anemia is reportedly of macrocytic type with azathioprine and MMF, and microcytic with sirolimus. Calcineurin inhibitors may cause anemia indirectly by impairing kidney function. However, the constant tempo of anemia throughout the post transplant course despite the gradual reduction of the immunosuppressive drug doses refutes the probability of drug related post transplant anemia.
The most important cause that we are inclined to is the erythropoietin insufficiency post kidney transplantation. [4] Erythrocytosis is usually more expected than anemia post renal transplantation. [5] However, both conditions denote massive derangement of erythropoietin homeostasis. In general, the reported anemia is of two kinds, either erythropoietin resistant or erythropoietin deficient. Erythropoietin resistant post transplant anemia is most probably secondary to bone marrow permanent damage caused by pretransplant uremic toxins, hyperparathyroidism, or primary erythroid progenitors disease, wherein endogenous erythropoietin level would be at its peak; [6] our patient revealed low serum erythropoietin level for the degree of anemia. There is a link between erythropoietin deficiency and the impaired GFR. [7],[8] Despite the fact that no kidney biopsy was performed in our patient because of the normal renal function, renal tubular dysfunction or interstitial nephritis due to low-grade immunologic inflammatory reaction (polyoma BK viral interstitial nephritis or CMV viral infection) that could cause erythropoietin deficiency was not ruled out.
Finally, the dramatic improvement of Hgb level after commencement of erythropoietin replacement therapy would negate the possibility of peripheral autoimmune destruction of the erythropoietin hormone. We speculate the presence of the generalized erythropoietin derangement inflicted by the transplant procedure or the immunosuppressive medications, or a donor-recipient erythropoietin incompatibility as possible causes of anemia in the presence of normal renal function.
In conclusion, this case highlights the notorious underestimation of the post transplant anemia secondary to erythropoietin deficiency in the kidney transplantation patients.
| References | | |
| 1. | Vanrenterghem Y, Ponticilli C, Morales JM, et al. Prevalence and management of anemia in renal transplant recipients: a European survey. Am J Transplant 2003;3:835. 
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| 2. | Egbuna O, Zand MS, Arbini A, et al. A cluster of parvovirus B19 infections in renal transplant recipients: a prospective case series and review of the literature. Am J Transplant 2006;6:225.
[PUBMED] [FULLTEXT] |
| 3. | Nayak SG, Kiran MK, Fernandes K, Gopalakrishna G, Shastry JC. Anemia in renal transplant recipients-a persisting problem. Indian J Nephrol 2005;15:239-42.
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| 4. | Zadrazil J, Horak P, Horcicka V, et al. Endo genous Erythropoitin levels and anemia in long-term renal transplant recipients. Kidney Blood Pressure Res 2007;30:108-16.
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| 5. | Charfeddine K, Zaghane S, Yaich S, et al. Factors predisposing to Post-Transplant Erythrocytosis: A retrospective study. Saudi J Kidney Dis Transplant 2008;19:371-8.
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| 6. | Joist H, Brennan DC, Coyne DW. Anemia in the kidney-transplant patient. Adv Chronic Kidney Dis 2006;13:4.
[PUBMED] [FULLTEXT] |
| 7. | Tukowski-Duhem A, Kamar N, Cointault O, et al. Predictive factors of anemia within the first year post renal transplant. Transplantation 2005;80(7):903-9.
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| 8. | Sezer S, Ozderm F, Tutal E, Bilgic A, Haberal M. Prevalence and etiology of anemia in renal transplant recipients. Transplant Proc 2006;38 (2):537-40.
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Correspondence Address:
Wael Latif Jabur
New Medical Center Specialty Hospital, P.O. Box 7832, Dubai
United Arab Emirates
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PMID: 21196622 
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