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Risk factors of post renal transplant anaemia among Sudanese patients, a study in three renal transplant centres
© Banaga et al; licensee BioMed Central Ltd. 2011
Received: 29 March 2011
Accepted: 9 August 2011
Published: 9 August 2011
There is a relative lack of recent information about late post kidney transplantation anaemia (PTA), especially in the developing countries; data are scarce about the prevalence and risk factors of PTA. Sudan was a leading country in Africa and Arab world in kidney transplantation. The first kidney transplantation in Sudan was in 1973.
This is a cross-sectional hospital analytic study enrolling all kidney transplanted recipients following in the transplant referral clinics at Ahmed Gassim, Selma and Ibn Sina Hospitals, Khartoum/Sudan, in the period from 1/8/2010 to 1/9/2010, clinical and laboratory data were obtained from 114 patients, anaemia was defined as Hb levels of < 13 g/dl for male patients and < 12 g/dl for female patients, exclusion criteria were pregnancy, below 18 years old patients, multiple organ transplantation, and patients with less than one year from the transplantation.
The study showed that 39.5% of the patients were anaemic. Univariate analysis showed that late PTA is significantly associated with not using Erythropoietin (EPO) in the pre-transplant period (p = < 0.001), history of rejection (p = 0.003), longer time from transplantation (p = 0.015), and eGFR (p < 0.0001). Multivariate analysis showed that eGFR (p = < 0.001) and not use of EPO in the pre transplant period (p < 0.001) are strong predictors of PTA. The use of Angiotensin converting enzyme inhibitors/Angiotensin receptors blockers (ACEI/ARB), immunosuppressive treatments, presence or absence of co-morbidities, donor type and donor age are not significantly associated with late PTA.
The study concluded that late PTA is common and under recognized. Risk factors for late PTA include renal dysfunction, history of rejection, longer duration of transplantation and not using EPO in the pre-transplant period. Renal dysfunction and not using EPO in the pre-transplant period are major predictors of late PTA.
Anaemia in End Stage Renal Failure (ESRF) is mainly due to loss of the endocrine function of the kidneys that lead to deficiency of erythropoietin (EPO) and development of anaemia. Many studies pointed out the prevalence of Post transplant Anaemia (PTA) in developed countries, a Japanese study concluded that the prevalence of PTA is 20% , a big multicenter study conducted in 72 centers in 16 European countries [Transplant European Survey on Anaemia Management (TRESAM)] concluded that the prevalence of PTA was 38.6% . In a published British study, the prevalence of anaemia was 53% at 12 months from the kidney transplantation . A Turkish study concluded that prevalence of PTA was 49.3% , in Austria PTA was present in 39.7% . Among Hungarians, PTA was 33.8% .
Renal dysfunction is strongly associated with development of PTA [2, 7–18] and considered as a major risk factor, other risk factors like rejection [9, 19, 20], recent infections [21–24], longer duration from transplantation , immunosuppressive treatments [3, 25–32], use of Angiotensin converting enzyme inhibitors/Angiotensin receptors blockers (ACEI/ARB) [2, 12, 13, 33, 34], low serum albumin , protein energy waste syndrome , and old age of the kidney donor  are all considered as risk factors for development of PTA.
Our aim in this study is to identify the prevalence of late PTA (> 1 year post transplant) and the risk factors of late PTA among adult Sudanese kidney recipients.
Study population & Data collection
This study is a cross sectional hospital base analytic study. The subjects of the study are all kidney transplanted recipients following in the transplant referral clinics at Ahmed Gassim, Selma & Ibn Sina Hospitals, Khartoum/Sudan. All patients attending the transplant referral clinics between (1/8/2010 - 1/9/2010) were interviewed by questionnaire focusing on personal and clinical data exploring (time on dialysis, receiving EPO treatment during dialysis, period of transplantation, donor age, immunosuppressive regimen, The use of ACEI/ARB, history of rejection, and presence or absence of co-morbidities) with a review of their medical files. All laboratory investigations conducted at the time of the visit such as (complete blood count, peripheral blood picture, and renal functions) were reported. Estimated Glomerular Filtration rate (eGFR) was calculated using the abbreviated modification of diet in renal disease (MDRD) study formula . The research was in compliance of the declaration of Helsinki and approved by ethics and research committees in the local hospitals, an informed consent was obtained from each patient participated in the study
Anaemia was defined as Hb levels of < 13 g/dl for male patients and < 12 g/dl for female patients this targets were selected based on the WHO guidelines & the American Society of Transplantation .
Inclusion & exclusion criteria
We included all kidney transplant recipients who received a kidney transplant and attended the referral clinic at Ahmed Gassim, Selma and Ibn Sina Hospitals between 1/8 -1/9/2010. The exclusion criteria were Pregnancy, below 18 years old patients, multiple organ transplantation and patients with less than 1 year from the transplantation.
Categorical variables between the anaemic and non anaemic patients were compared using X 2 test, continues variables between the anaemic and non anaemic patients were compared using Student T-test. Multivariate linear regression analysis used to identify the predictors of PTA. Statistical analysis conducted using SPSS 18 software package (SPSS Inc, Chicago, IL, USA) and P value < 0.05 were considered significant.
The characteristics of the study population
Male 78 (68.4%)
Female 36 (31.6%)
42.4 ± 12.66
Unemployed 81 (71.1%)
Non professional 16 (14%)
Professional 17 (14.9%)
Living related donor: 99 (86.8%)
Living unrelated: 15 (13.2%)
History of acute rejectiona
Yes 13 (11.4%) No 101 (88.6%)
Donor age (years)b
28.9 ± 7.6
Use of EPO pre-transplanta
Yes 64 (56.1%) No 50 (43.9%)
Use of Mycofenolate mofetila
Yes 31 (27.2%) No 83(72.8%)
Use of Azathioprinea
Yes 80 (70.2%) No 34 (29.8%)
Use of Cyclosporinea
Yes 45 (39.5%) No 69 (60.5%)
Use of Tacrolimusa
Yes 65 (57%) No 49 (43%)
Use of ACEI/ARBa
Yes 23 (20.2%) No 91 (79.8%)
Yes 9 (7.9%) No 105 (92%)
Time on Dialysis (months)b
14.6 ± 13
Period of kidney transplantation (months)b
49 ± 42.26
12.7 ± 1.96
1.4 ± 0.88
39.17 ± 19.5
eGFR ml/min/1.732 b
81.6 ± 34.3
Risk factors of post transplant anaemia
Non anaemic group
42.9 ± 12. 9
42 ± 12.7
Use of (EPO) pre transplanta
Donor type a
History of rejectiona
Use of Mycofenolate mofetila
Use of Azathioprinea
Use of Cyclosporinea
Use of Tacrolimusa
Use of ACEI/ARBa
Presence of Co-Morbidities
Time on dialysis (months)b
12.9 ± 11.6
15.7 ± 13.8
Time since transplantation (months)b
62.1 ± 51.5
40.5 ± 33.02
Donor age (years)b
29.3 ± 7
28.5 ± 8
56.8 ± 20.7
97.7 ± 31.8
Liner regression model of serum haemoglobin as dependant variable (r = 0.626, p = < 0.0001)
Presence or absence of Co-morbidities
Time since transplantation
History of rejection
Use of EPO
Prevalence of Late PTA
Published literature on PTA is limited, especially in developing countries, this is due to lack of transplantation facilities which lead to deficiency on PTA published data, this study is the first Sudanese study on prevalence and risk factors of late PTA. Our result showed that 39.5% of kidney transplanted patients have anaemia. This high prevalence indicates the severity of this problem among Sudanese renal transplanted population; our result is higher than many of the published literature in the developed countries. Prevalence of PTA in Japan is 20% . In other American study it was 26% in 5 years post transplant . In the European TRESAM study it was 38% . In Austria, PTA was present in 39.7% . Among Hungarians, PTA was 33.8% . In other hand data published from Asia and South America showed higher prevalence of PTA, in Turkey PTA was present among 49.3% of transplanted patients , PTA in Argentina was 42.2% .
The characteristics of the study population
In our study, we reviewed 114 patients, 68% were males, Live related donors constitute 86.6% of the donor type with no cadaveric donors in our study population; this is very different from the other major published literature from the developed countries where cadaveric donors are the major donor type in kidney transplantation. 43.9% of this study population didn't receive EPO during dialysis because of financial reasons which reflects poor management of anaemia among our patients in the pre-transplant period. The mean age in this study was 42 years. Only 9 patients have co-morbidities mainly (Liver diseases, Diabetes mellitus and Heart diseases). Despite that renal transplantation improves the quality of life of the patients; unemployment rate is high among kidney recipients 71.1%
Risk factors for PTA
After univariate analysis of the variables, history of rejection was associated with anaemia (p = 0.003), this result agrees with many of published articles which stated that rejection is a leading cause for anaemia [9, 19, 20].
Renal dysfunction was strongly associated with anaemia; in our study, anaemic patients have mean of eGFR of 56 ml/min/1.732 (p = < 0.0001), this result is going with the majority of published literature on PTA suggesting renal dysfunction as major cause of PTA [2, 7–18].
Patients with longer duration of transplantation have more tendency to develop late PTA (p = 0.015), this is agrees with many literature which pointed out the increase prevalence of anaemia in the late post-transplant period in comparison with early post-transplant period , this is also can be explained by the fact that chronic allograft nephropathy can occur after long time from transplantation and that may lead to development of PTA.
In this study not using of EPO before transplantation was a major risk factor for PTA (p < 0.0001), so patients may still have significant anaemia at time of transplantation. Use of EPO pre transplant is associated with better 5 year graft survival and reduce frequency of rejection , concerning the level of EPO in the post transplant period, in a study compared two groups (anaemic & non-anaemic) of renal transplant recipients with normal renal functions, EPO deficiency and resistance play a causative role for PTA , however in other study no relation was found between administration of the EPO and anaemia, the same result favoring use of EPO only on high risk patients .
Multivariate analysis showed that renal dysfunction and not using EPO before transplantation were major predictors for PTA.
In this result, immunosuppressive treatment was not associated with anaemia this is contradicting with the majority of the literature which stating the strong relationship [3, 25–32], however another study found no relation between anaemia and some combinations of immunosuppressive treatments  and perhaps live related transplantation needing less immunosuppressive treatments may be the curl print point.
In this study there was no relation between ACEI/ARB and late PTA, the literature concerning that is controversial with some favoring the link between PTA and ACEI/ARB [2, 12, 13, 33, 34] and other articles denied the relationship [15, 17].
Our study had many limitations that need to be recognized, we didn't have data on iron stores and serum albumin this is mainly due to lack of financial recourses, medical data about the exact nature and details of co-morbidities was difficult to obtain, so we just asked our patients about nature and presence or absence of co morbidities. Data about numbers and treatment of rejection and history of blood transfusions was not collected.
The study concluded that late PTA is common and under recognized. Risk factors for late PTA include renal dysfunction, history of rejection, longer duration of transplantation and not using EPO in the pre-transplant period. Renal dysfunction and not using EPO in the pre-transplant period are major predictors of PTA.
The authors thanks the patients and the staff in Ahmed Gassim, Ibn Sina and Dr. Selma hospitals, Khartoum, Sudan, for contribution in this study,
- Saito S, Fujiwara T, Sakagami K, Matsuno T, Tanaka N: Anemia following renal transplantation. Transplant Proc. 1998, 30 (7): 3025-3026. 10.1016/S0041-1345(98)00914-2.View ArticlePubMedGoogle Scholar
- Vanrenterghem Y, Ponticelli C, Morales JM, Abramowicz D, Baboolal K, Eklund B, Kliem V, Legendre C, Morais Sarmento AL, Vincenti F: Prevalence and management of anemia in renal transplant recipients: a European survey. Am J Transplant. 2003, 3 (7): 835-845. 10.1034/j.1600-6143.2003.00133.x.View ArticlePubMedGoogle Scholar
- Borrows R, Loucaidou M, Chusney G, Borrows S, Tromp JV, Cairns T, Griffith M, Hakim N, McLean A, Palmer A, et al: Anaemia and congestive heart failure early post-renal transplantation. Nephrol Dial Transplant. 2008, 23 (5): 1728-1734. 10.1093/ndt/gfm815.View ArticlePubMedGoogle Scholar
- Unal A, Sipahioglu MH, Akcakaya M, Tokgoz B, Sav T, Oymak O, Utas C: An underappreciated problem in renal transplant recipients: anemia. Transplant Proc. 2008, 40 (5): 1399-1403. 10.1016/j.transproceed.2008.03.080.View ArticlePubMedGoogle Scholar
- Lorenz M, Kletzmayr J, Perschl A, Furrer A, Horl WH, Sunder-Plassmann G: Anemia and iron deficiencies among long-term renal transplant recipients. J Am Soc Nephrol. 2002, 13 (3): 794-797.PubMedGoogle Scholar
- Molnar MZ, Czira M, Ambrus C, Szeifert L, Szentkiralyi A, Beko G, Rosivall L, Remport A, Novak M, Mucsi I: Anemia is associated with mortality in kidney-transplanted patients--a prospective cohort study. Am J Transplant. 2007, 7 (4): 818-824. 10.1111/j.1600-6143.2006.01727.x.View ArticlePubMedGoogle Scholar
- Yorgin PD, Scandling JD, Belson A, Sanchez J, Alexander SR, Andreoni KA: Late post-transplant anemia in adult renal transplant recipients. An under-recognized problem?. Am J Transplant. 2002, 2 (5): 429-435. 10.1034/j.1600-6143.2002.20506.x.View ArticlePubMedGoogle Scholar
- Choukroun G, Deray G, Glotz D, Lebranchu Y, Dussol B, Bourbigot B, Lefrancois N, Cassuto-Viguier E, Toupance O, Hacen C, et al: [Incidence and management of anemia in renal transplantation: an observational-French study]. Nephrol Ther. 2008, 4 (7): 575-583.View ArticlePubMedGoogle Scholar
- Muirhead N: Erythropoietin and renal transplantation. Kidney Int Suppl. 1999, 69: S86-92.View ArticlePubMedGoogle Scholar
- Shibagaki Y, Shetty A: Anaemia is common after kidney transplantation, especially among African Americans. Nephrol Dial Transplant. 2004, 19 (9): 2368-2373. 10.1093/ndt/gfh256.View ArticlePubMedGoogle Scholar
- Sezer S, Ozdemir FN, Tutal E, Bilgic A, Haberal M: Prevalence and etiology of anemia in renal transplant recipients. Transplant Proc. 2006, 38 (2): 537-540. 10.1016/j.transproceed.2005.12.067.View ArticlePubMedGoogle Scholar
- Gentil MA, Perez-Valdivia MA, Lopez-Mendoza M, Ortega F, Arias M, Gomez-Alamillo C, Campistol JM: Factor deficiency in the anemia of renal transplant patients with grade III-IV chronic kidney disease: baseline results of the ARES Study. Transplant Proc. 2008, 40 (9): 2922-2924. 10.1016/j.transproceed.2008.08.083.View ArticlePubMedGoogle Scholar
- Shah N, Al-Khoury S, Afzali B, Covic A, Roche A, Marsh J, Macdougall IC, Goldsmith DJ: Posttransplantation anemia in adult renal allograft recipients: prevalence and predictors. Transplantation. 2006, 81 (8): 1112-1118. 10.1097/01.tp.0000205174.97275.b5.View ArticlePubMedGoogle Scholar
- Turkowski-Duhem A, Kamar N, Cointault O, Lavayssiere L, Ribes D, Esposito L, Fillola G, Durand D, Rostaing L: Predictive factors of anemia within the first year post renal transplant. Transplantation. 2005, 80 (7): 903-909. 10.1097/01.tp.0000173791.42893.08.View ArticlePubMedGoogle Scholar
- Sinnamon KT, Courtney AE, Maxwell AP, McNamee PT, Savage G, Fogarty DG: Level of renal function and serum erythropoietin levels independently predict anaemia post-renal transplantation. Nephrol Dial Transplant. 2007, 22 (7): 1969-1973. 10.1093/ndt/gfm100.View ArticlePubMedGoogle Scholar
- Ott U, Busch M, Steiner T, Wolf G: Anemia after renal transplantation: an underestimated problem. Transplant Proc. 2008, 40 (10): 3481-3484. 10.1016/j.transproceed.2008.07.139.View ArticlePubMedGoogle Scholar
- Molnar MZ, Novak M, Ambrus C, Kovacs A, Pap J, Remport A, Szeifert L, Mucsi I: Anemia in kidney transplanted patients. Clin Transplant. 2005, 19 (6): 825-833. 10.1111/j.1399-0012.2005.00428.x.View ArticlePubMedGoogle Scholar
- Fernandez Fresnedo G, Palomar R, Rodrigo E, Ruiz JC, de Francisco AL, Cotorruelo JG, Arias M: Prevalence of anemia in renal transplant patients: results from MOST, an observational trial. Transplant Proc. 2005, 37 (9): 3821-3822. 10.1016/j.transproceed.2005.10.054.View ArticlePubMedGoogle Scholar
- Moulin B, Ollier J, George F, Purgus R, Roux F, Sampol J, Olmer M: Serum erythropoietin and reticulocyte maturity index after renal transplantation: a prospective longitudinal study. Nephron. 1995, 69 (3): 259-266. 10.1159/000188467.View ArticlePubMedGoogle Scholar
- Chua MS, Barry C, Chen X, Salvatierra O, Sarwal MM: Molecular profiling of anemia in acute renal allograft rejection using DNA microarrays. Am J Transplant. 2003, 3 (1): 17-22. 10.1034/j.1600-6143.2003.30104.x.View ArticlePubMedGoogle Scholar
- Kumar V, Gupta S, Singh S, Goyal VK, Yadav M: Pure red cell aplasia associated with cytomegalovirus infection. J Pediatr Hematol Oncol. 2010, 32 (4): 315-316. 10.1097/MPH.0b013e3181cb4383.View ArticlePubMedGoogle Scholar
- So BJ, Chae KM, Lee KK, Lee YJ, Jeong BH: Pure red cell aplasia due to parvovirus B19 infection in a renal transplant patient: a case report. Transplant Proc. 2000, 32 (7): 1954-1956. 10.1016/S0041-1345(00)01509-8.View ArticlePubMedGoogle Scholar
- Vales-Albertos LJ, Garcia-Cardenas M, Chavez-Becerra S, Gomez-Navarro B, Monteon-Ramos F, Cueto-Manzano AM: Pure red cell aplasia associated with parvovirus B19 infection in renal transplantation: the first case report in Mexico. Transplantation. 2005, 79 (6): 739-10.1097/01.TP.0000149339.25047.F4.View ArticlePubMedGoogle Scholar
- Karras A, Thervet E, Legendre C: Hemophagocytic syndrome in renal transplant recipients: report of 17 cases and review of literature. Transplantation. 2004, 77 (2): 238-243. 10.1097/01.TP.0000107285.86939.37.View ArticlePubMedGoogle Scholar
- Kuypers DR, de Jonge H, Naesens M, de Loor H, Halewijck E, Dekens M, Vanrenterghem Y: Current target ranges of mycophenolic acid exposure and drug-related adverse events: a 5-year, open-label, prospective, clinical follow-up study in renal allograft recipients. Clin Ther. 2008, 30 (4): 673-683. 10.1016/j.clinthera.2008.04.014.View ArticlePubMedGoogle Scholar
- Engelen W, Verpooten GA, Van der Planken M, Helbert MF, Bosmans JL, De Broe ME: Four cases of red blood cell aplasia in association with the use of mycophenolate mofetil in renal transplant patients. Clin Nephrol. 2003, 60 (2): 119-124.View ArticlePubMedGoogle Scholar
- Ourahma S, Mercadal L, Tezenas du Montcel S, Assogba D, Bitker MO, Mallet A, Barrou B: Anemia in the period immediately following renal transplantation. Transplant Proc. 2007, 39 (5): 1446-1450. 10.1016/j.transproceed.2006.12.036.View ArticlePubMedGoogle Scholar
- Geiger C, Foller M, Herrlinger KR, Lang F: Azathioprine-induced suicidal erythrocyte death. Inflamm Bowel Dis. 2008, 14 (8): 1027-1032. 10.1002/ibd.20433.View ArticlePubMedGoogle Scholar
- Rigatto C: Anemia, renal transplantation, and the anemia paradox. Semin Nephrol. 2006, 26 (4): 307-312. 10.1016/j.semnephrol.2006.05.007.View ArticlePubMedGoogle Scholar
- Agrawal A, Parrott NR, Riad HN, Augustine T: Azathioprine-induced pure red cell aplasia: case report and review. Transplant Proc. 2004, 36 (9): 2689-2691. 10.1016/j.transproceed.2004.09.047.View ArticlePubMedGoogle Scholar
- Khosroshahi HT, Asghari A, Estakhr R, Baiaz B, Ardalan MR, Shoja MM: Effects of azathioprine and mycophenolate mofetil-immunosuppressive regimens on the erythropoietic system of renal transplant recipients. Transplant Proc. 2006, 38 (7): 2077-2079. 10.1016/j.transproceed.2006.06.043.View ArticlePubMedGoogle Scholar
- Willerding-Mollmann S, Wilkens L, Schlegelberger B, Kaiser U: [Azathioprine-associated myelodysplastic syndrome with cytogenetic aberrations]. Dtsch Med Wochenschr. 2004, 129 (22): 1246-1248. 10.1055/s-2004-826853.View ArticlePubMedGoogle Scholar
- Naito M, Kawashima A, Akiba T, Takanashi M, Nihei H: Effects of an angiotensin II receptor antagonist and angiotensin-converting enzyme inhibitors on burst forming units-erythroid in chronic hemodialysis patients. Am J Nephrol. 2003, 23 (5): 287-293. 10.1159/000072705.View ArticlePubMedGoogle Scholar
- Le Meur Y, Lorgeot V, Comte L, Szelag JC, Aldigier JC, Leroux-Robert C, Praloran V: Plasma levels and metabolism of AcSDKP in patients with chronic renal failure: relationship with erythropoietin requirements. Am J Kidney Dis. 2001, 38 (3): 510-517. 10.1053/ajkd.2001.26839.View ArticlePubMedGoogle Scholar
- Molnar MZ, Czira ME, Rudas A, Ujszaszi A, Haromszeki B, Kosa JP, Lakatos P, Beko G, Sarvary E, Varga M, et al: Association between the malnutrition-inflammation score and post-transplant anaemia. Nephrol Dial Transplant. 2011, 26 (6): 2000-2006. 10.1093/ndt/gfq690.View ArticlePubMedGoogle Scholar
- Levey AS, Greene T, Kusek JW, Beck GL: A simplified equation to predict glomerular filtration rate from serum creatinine (abstract). J Am Soc Nephrol. 2000, 11 (155A):Google Scholar
- Kasiske BL, Vazquez MA, Harmon WE, Brown RS, Danovitch GM, Gaston RS, Roth D, Scandling JD, Singer GG: Recommendations for the outpatient surveillance of renal transplant recipients. American Society of Transplantation. J Am Soc Nephrol. 2000, 11 (Suppl 15): S1-86.PubMedGoogle Scholar
- Petrone H, Arriola M, Re L, Taylor F, Bruzzone M, Chiurchu C, Schiavelli R: National survey of anemia prevalence after kidney transplantation in Argentina. Transplant Proc. 2010, 42 (1): 288-290. 10.1016/j.transproceed.2009.12.053.View ArticlePubMedGoogle Scholar
- Lietz K, Lao M, Paczek L, Gorski A, Gaciong Z: The impact of pretransplant erythropoietin therapy on late outcomes of renal transplantation. Ann Transplant. 2003, 8 (2): 17-24.PubMedGoogle Scholar
- Nampoory MR, Johny KV, al-Hilali N, Seshadri MS, Kanagasabhapathy AS: Erythropoietin deficiency and relative resistance cause anaemia in post-renal transplant recipients with normal renal function. Nephrol Dial Transplant. 1996, 11 (1): 177-181.View ArticlePubMedGoogle Scholar
- Van Biesen W, Vanholder R, Veys N, Verbeke F, Lameire N: Efficacy of erythropoietin administration in the treatment of anemia immediately after renal transplantation. Transplantation. 2005, 79 (3): 367-368. 10.1097/01.TP.0000150370.51700.99.View ArticlePubMedGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2369/12/37/prepub
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