| Abstract|| |
In some renal allograft recipients, anemia persists or develops following transplantation. Anemia is associated with pre-operative blood loss and allograft dysfunction, including delayed graft function, acute rejection and chronic allograft dysfunction. To study the prevalence and association of post-renal transplant anemia, we studied 200 renal transplant recipients; 131 (65.5%) patients were males and 69 (34.5%) patients were females, and age ranged from 17 to 67 years, with a mean of 37.7 ± 10.8 years. All patients were receiving cyclosporine, prednisolone and mycophenolate mofetil (MMF). Complete blood count was done at two times: three and six months post-renal transplant. There were 74% anemic patients three months after renal transplantation and 45% anemic patients six months after renal transplantation. High creatinine value, female gender, delayed graft function, episodes of acute rejection, perioperative blood loss and infections were the only significant independent risk factors for prevalence of anemia post-renal transplant. In our study, we did not find an association between MMF and cyclosporine nor angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptors blocker (ARBs) with anemia. This study demonstrates that anemia is a common complication during the first six months after kidney transplantation, with several risk factors precipitating this complication.
|How to cite this article:|
Elsayed H, Sany D, Eldin EN, El-shahawy Y, Shawki S, Aziz A. Prevalence and association of post-renal transplant anemia. Saudi J Kidney Dis Transpl 2012;23:461-6
|How to cite this URL:|
Elsayed H, Sany D, Eldin EN, El-shahawy Y, Shawki S, Aziz A. Prevalence and association of post-renal transplant anemia. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2020 Aug 13];23:461-6. Available from: http://www.sjkdt.org/text.asp?2012/23/3/461/95703
| Introduction|| |
Kidney transplantation is the renal replacement modality of choice for patients with endstage renal disease.  However, renal transplant recipients are increasingly recognized as a specific category of persons with chronic kidney disease (CKD) at risk of a progressive fall in glomerular filteration rate GFR with associated complications. 
Following successful renal transplantation, correction of anemia occurs via endogenous production of erythropoietin from the engrafted kidney, but about one-third of the subjects may remain anemic. ,
Early post-transplant anemia (PTA) refers to anemia persisting or arising relatively soon after engraftment. Relevant potential etiological factors include iron deficiency, infectious agents, donor age and immunosuppressive therapy. "Late" PTA is associated with a decline in renal function observed in the context of chronic allograft nephropathy or recurrent renal pathology. 
In the context of CKD, anemia is associated with poor quality of life, exercise tolerance, mental agility, renal and cardiac dysfunction, increased hospitalization and reduced survival on dialysis. , Similar to dialyzed patients, cardiovascular diseases are the leading cause of death in the kidney-transplanted population. Anemia is an independent predictor of both left ventricular hypertrophy and congestive heart failure and, therefore, mortality in transplanted patients. 
Reported causes of anemia in transplant recipients may include iron deficiency, vitamin B 12 and folic acid deficiency,  relative or absolute erythropoietin deficiency or resistance primarily caused by impaired allograft function including acute rejection or delayed graft function, use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) and autoimmune disease such as systemic lupus erythematosus (SLE), malignancy or infection including cytomegalovirus (CMV) or parvovirus B19 infection.  The use of immunosuppressive drugs is also well documented to be associated with post-transplant anemia, e.g. azathioprine (AZA), mycophenolate mofetil (MMF) rapamycin and calcineurin inhibitors. 
Our study aimed to determine the prevalence and risk factors of post-renal transplant anemia in our population.
| Materials and Methods|| |
We studied 200 kidney transplant recipients who finished at least six months of post-transplant follow-up at the National Institute of Urology and Nephrology from January 2008 to January 2009. The following data were collected about the patients:
- Clinical history and examinations, including etiology of previous CKD, duration of dialysis, transplantation as well as the source of the graft.
- Kidney function tests and complete blood picture at 2 times: three and six months post-renal transplant.
- Appropriate laboratory tests whenever indicated.
| Statistical Analysis|| |
The data collected were reviewed, coded and entered into a PC where statistical analysis was done using SPSS (statistical package for social science) version. The quantitative variables were expressed as the mean, SD and range. Chi-square test was used to compare qualitative variables between groups. Unpaired t-test was used to compare quantitative variables in parametric data (SD <50% mean). The Mann Whitney test was used instead of unpaired t-test in non-parametric data (SD >50% mean). The correlation coefficient test was used to rank different variables against each other positively or inversely. P-value <0.05 was considered as significant.
| Results|| |
There were 131 (65.5%) male patients and 69 (34.5%) female patients in the study. The age ranged from 17 to 67 years, with a mean of 37.7 ± 10.8 years.
Hemodialysis duration of patients prior to renal transplantation ranged from 0 to 68 months, with a mean of 16.3 ± 16.4 months. Two patients had pre-emptive renal transplanation. The most common causes of renal failure are shown in [Figure 1]. All patients received grafts from living donors.
|Figure 1: Causes of renal failure and its percent: the most common causes of renal failure were unknown (36.5%) and hypertension (21.5%)|
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Laboratory data of patients at three and six months after renal transplantation are shown in [Table 1]. There was a highly significant difference between hemoglobin (Hgb) levels at three months and at six months (P <0.001).
|Table 1: The mean and range of the different parameters at three and six months after transplantation.|
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Taking cut-off values for Hgb (13 mg/dL for males and 12 mg/dL for females), we found 148 anemic patients three months after renal transplantation and 90 at six months after renal transplantation (P <0.001).
Four (2%) patients had delayed graft function. There was a highly significant difference between the frequency of acute rejection at three months and six months after renal transplantation (P <0.001).
Infection was common after transplantation, but there was no significant difference between frequency of infection at three months and at six months after renal transplantation (P >0.05). All the patients received cyclosporine, prednisolone and MMF. Only 13 patients (6.5%) received ACEIs.
There was a highly significant positive correlation between the Hgb levels and age [Figure 2]. In addition, there was a highly significant negative correlation between the Hgb levels versus serum creatinine [Figure 3], also highly significant negative correlation with serum creatinine levels at three and six months after transplantation [Table 2] and [Table 3].
|Figure 2: There is a highly significant positive correlation between hemoglobin (Hb) and age.|
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|Figure 3: There is a highly significant negative correlation between hemoglobin (HB) and serum creatinine.|
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|Table 2: Correlation of the different parameters and hemoglobin (Hgb) in the study patients at three months.|
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|Table 3: Correlation of the different parameters and hemoglobin (Hgb) in the study patients at six months.|
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There was a highly significant difference between males and females, patients with infection and those without and patients with acute rejection and those without regarding the Hgb levels at three and six months after renal transplantation (P <0.001), but there was no significant correlation between the Hgb levels and the source of the graft or the use of ACEI.
There was no significant difference between males and females at three months, but a significant difference at six months regarding the frequency of anemia (P <0.001) [Table 4]. Our study showed significant negative correlation between hemoglobin levels and total WBCs count [Figure 4]. Furthermore, there was a significant difference between the patients with infection and those without regarding the frequency of anemia at three months after transplantation (P <0.05) and highly significant difference at six months (P <0.001) [Table 4], but there was only a significant difference between the patients with delayed graft function and those without regarding the frequency of anemia at six months after transplantation (P <0.05).
|Figure 4: There is a significant negative correlation between hemoglobin (HB) and WBCs.|
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|Table 4. Association of gender with the frequency of anemia six months after transplantation.|
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On the other hand, there was no significant difference between the patients with related donors and those without, the patients with acute rejection and those without, the patients receiving ACEI and those not regarding the frequency of anemia at three months and six months after transplantation. Furthermore, there was no significant difference between the patients with persistent hyperparathyroidism and those without regarding the frequency of anemia at six months after transplantation.
| Discussion|| |
Among the possible risk factors listed above, we found that a higher creatinine value, female gender, delayed graft function, episodes of acute rejection and infections were the only significant independent risk factors of occurence of anemia in transplanted kidney patients.
The Hgb levels should be completely normalized by six months for most renal transplant patients as long as they have a good allograft function. However, in some patients, anemia persists or develops following transplantation. Most of them are associated with pre-operative blood loss and allograft dysfunction (delayed graft function, acute rejection, chronic allograft dysfunction), although some patients may have anemia with normal allograft function as well. 
In our study, anemia was common, as has been reported elsewhere. The prevalence of anemia ranges from 30% to 40% of patients. ,,, Although it is difficult to compare each of these studies because of the different definitions of anemia and timings of checking, it is very important to note that all the studies including ours confirmed the high prevalence of mild anemia after renal transplantation.
Reported causes of anemia in transplant recipients are many, including the different immunosuppressive drugs. ,,,, In addition, hyperparathyroidism can be a cause of anemia, as 21% of the transplant recipients still show abnormally high levels of parathyroid hormone even many years after transplantation. ,,, In our study, there was no significant difference between the patients with hyperparathyroidism and those without regarding the frequency of anemia at six months after transplantation. This is because the parathyroid hormone levels were obtained for only 21 patients (small sample of non-primary point).
More females than males had anemia at six months, and this may be due to regain of the menstruation after improvement of the kidney function tests and general condition.  However, other studies showed a higher prevalence of anemia in males. ,
The European study showed that use of ACEIs, ARBs or MMF was associated with a higher prevalence of anemia.  Our study did not find an association of the use of ACEIs or ARBs with anemia because very few patients were on ACEIs or ARBs. In addition, we did not find an association of the use of MMF and Cyclosporine with the frequency of anemia; this may be due to the shorter duration of our study (six months) in contrast to the longer duration of the European study, which allows for more side effects of immunosuppressive drugs to develop. 
We conclude that our study proved that anemia is a common complication during the first six months after kidney transplantation. This is mostly due to perioperative blood loss, infections, rejections and graft dysfunction. Furthermore, female gender was found to be a risk factor in the development of anemia after kidney transplantation.
| References|| |
|1.||Meyers CM, Kirk AD. Workshop on late renal allograft dysfunction. Am J Transplant 2005; 5:1600-5. |
|2.||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;22:1969-73. |
|3.||Vanrenterghem Y, Ponticelli C, Morales JM, et al. Prevalence and management of anemia in renal transplant recipients: a European survey. Am J Transplant 2003;3:835-45. |
|4.||Shibagaki Y, Shetty A. Anaemia is common after kidney transplantation, especially among African Americans. Nephrol Dial Transplant 2004;19:2368-73. |
|5.||Roger SD, McMahon LP, Clarkson A, et al. Effects of early and late intervention with epoetin alpha on left ventricular mass among patients with chronic kidney disease (stage 3 or 4): results of a randomized clinical trial. J Am Soc Nephrol 2004;15:148-56. |
|6.||Gouva C, Nikolopoulos P, Ioannidis JP, Siamopoulos KC. Treating anaemia early in renal failure patients slows the decline of renal function: a randomized controlled trial. Kidney Int 2004;66:753-60. |
|7.||Molnar MZ, Czira M, Ambrus C, et al. Anemia Is Associated with Mortality in Kidney-Transplanted Patients. Am J Transplant 2007; 7:818-24. |
|8.||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: 794-7. |
|9.||Geetha D, Zachary JB, Baldado HM, Kronz JD, Kraus ES. Pure red cell aplasia caused by Parvovirus B19 infection in solid organ transplant recipients: a case report and review of literature. Clin Transplant 2000;14:586-91. |
|10.||Anonymous. Mycophenolate mofetil in renal transplantation: 3 year results from the placebo-controlled trial. European Mycophenolate Mofetil Cooperative Study Group. Transplantation 1999;68:391-6. |
|11.||Shibagaki Y, Shetty A. Anaemia is common after kidney transplantation, especially among African Americans. Nephrol Dial Transplant 2004;19: 2368-73. |
|12.||Miles AM, Markell MS, Daskalakis P, et al. Anemia following renal transplantation: erythropoietin response and iron deficiency. Clin Transplant 1997;11:313-. |
|13.||Yorgin PD, Belson A, Sanchez J, et al. Unexpectedly high prevalence of post transplant anemia in pediatric and young adult renal transplant recipients. Am J Kidney Dis 2002b; 40:1306-18. |
|14.||Mix TC, Kazmi W, Khan S, et al. Anemia: a continuing problem following kidney transplantation. Am J Transplant 2003;3:1426-33. |
|15.||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; 11:177-81. |
|16.||Gossmann J, Kachel HG, Schoeppe W, Scheuermann EH. Anemia in renal transplant recipients caused by concomitant therapy with azathioprine and angiotensin converting enzyme inhibitors. Transplantation 1993;56: 585-9. |
|17.||Geetha D, Zachary JB, Baldado HM, Kronz JD, Kraus ES. Pure red cell aplasia caused by Parvovirus B19 infection in solid organ transplant recipients: a case report and review of literature. Clin Transplant 2000;14:586-91. |
|18.||Ponticelli C, MacDonald AS, Rajagopalan P, Sindhi R, Mathew T. Phase III trial of Rapamune versus placebo in primary renal allograft recipients. Transplant Proc 2001;33: 2271-2. |
|19.||Abraham KA, Little MA, Dorman AM, Walshe JJ. Hemolytic-uremic syndrome in association with both cyclosporine and tacro-limus. Transplant Int 2000;13:443-7. |
|20.||Evenepoel P, Claes K, Kuypers DR, Debruyne F, Vanrenterghem Y. Parathyroidectomy after successful kidney transplantation: a single centre study. Nephrol Dial Transplant 2007;22: 1730-7. |
|21.||Dumoulin G, Hory B, Nguyen NU, et al. Lack of increased urinary calcium-oxalate supersaturation in long-term kidney transplant recipients. Kidney Int 1997;51:804-10. |
|22.||Heaf J, Tvedegaard E, Kanstrup IL, Fogh-Andersen N. Bone loss after renal transplantation: role of hyperparathyroidism, acidosis, cyclosporine and systemic disease.Clin Transplant 2000;14:457-63. |
|23.||Gogusev J, Duchambon P, Hory B, et al. Depressed expression of calcium receptor in parathyroid gland tissue of patients with hyperparathyroidism. Kidney Int 1997;51:328-36. |
|24.||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;2:429-35. |
Division of Renal Disease, Faculty of Medicine, Ain Shams University, Abbasia Square, Cairo
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4]