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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2004  |  Volume : 15  |  Issue : 4  |  Page : 433-439
Post-Transplant Erythrocytosis: A Review of 47 Renal Transplant Recipients

Department of Nephrology, Kanoo Kidney Center, Dammam Central Hospital, Dammam, Saudi Arabia

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Post-transplant erythrocytosis (PTE) is a well known phenomenon occurring in 5-17% of renal transplant recipients (RTR). In this retrospective study, we studied 47 RTR which included 39 males and eight females. They were divided into two groups according to the presence or absence of PTE, which was defined as a hematocrit of more than 51%. Nine of the 47 patients (19%) developed PTE all of whom were males. The mean age of patients with PTE was 44 ± 9 years versus 40 ±11 years for patients without PTE. The mean follow-up period was 113 ± 26 months and 93 ± 58 months for the PTE and non­PTE groups respectively. The mean period after transplant when PTE developed was 9.8 ± 9 months and it lasted for 37 ± 3 months. Thromboembolic complications in the form of lower limb deep vein thrombosis occurred in one patient. Most patients were treated with phlebotomies, and one received an angiotensin converting enzyme inhibitor. There were no apparent predisposing factors in any but one patient, who had autosomal dominant polycystic kidney disease and developed hydronephrosis of the transplanted kidney. This might have caused excessive production of erythropoietin resulting in PTE. The serum creatinine values were higher, although statistically insignificant in patients with PTE. Chronic rejection was more commonly seen in patients with PTE (44%) than those without PTE (11%). Our findings suggest that PTE is a benign condition affecting males more than females. It may have an association with chronic rejection. Most cases can be controlled using phlebotomy.

Keywords: Post transplant Erythrocytosis, ACE inhibitors, Deep vein thrombosis, Phlebotomy.

How to cite this article:
Abdelrahman M, Rafi A, Ghacha R, Qayyum T, Karkar A. Post-Transplant Erythrocytosis: A Review of 47 Renal Transplant Recipients. Saudi J Kidney Dis Transpl 2004;15:433-9

How to cite this URL:
Abdelrahman M, Rafi A, Ghacha R, Qayyum T, Karkar A. Post-Transplant Erythrocytosis: A Review of 47 Renal Transplant Recipients. Saudi J Kidney Dis Transpl [serial online] 2004 [cited 2022 Nov 29];15:433-9. Available from: https://www.sjkdt.org/text.asp?2004/15/4/433/32874

   Introduction Top

Post transplant erythrocytosis (PTE) is a well-known phenomenon occurring in 5-17% of renal transplant recipients (RTR). Although usually benign and transient, PTE may follow a more protracted course and in some instances, may cause thromboembolic complications. PTE is clinically defined as a persistent elevated hematocrit (HCT) greater than 51%. 1-2 It usually occurs within two years of engraft­ ment [1],[2]. PTE may remit on its own, but in many instances the hematocrit remains elevated for years [3],[4]. Its etiology is not yet fully under stood, but PTE probably represents an over production of erythropoietin (EPO) by the renal graft or by either native kidney, and/or to an unusually exaggerated response of the bone marrow to normal levels of erythropoietin. [5] A number of therapies are available for the management of PTE. These include serial phlebotomy, [2] native kidney nephrectomy, [6] theophylline [7] and angiotensin converting enzyme inhibitors (ACE-I), the last one beco­ming a standard form of therapy recently. [8],[9],[10],[11] In this retrospective study, we have reviewed the phenomenon of PTE in renal transplant patients followed-up for over a period of 113 months. The clinical profile of PTE, possible underlying causes, its complications and treat­ment modalities have been studied.

   Material and Methods Top

Records of 47 renal transplant recipients (RTR) on regular follow-up were reviewed on a random basis. These included 39 males and eight females with mean age of 44 ± 9 years. The mean period of follow-up was 113 ± 26 months. The patients were classified into two groups: group I with PTE (19% of patients i.e. 9 out of 47) and group II without PTE (81% i.e. 38 out of 47). In each group, the following were reviewed: age, sex, original renal disease, presence of hypertension, presence of diabetes mellitus, smoking habits, immunosuppression regimen, antihypertensive medications, different risk factors for PTE, date of onset and duration of PTE, complications, modality of treatment and the renal functions at the onset and at the end of the follow-up period. PTE was defined as a HCT of more than 51%. Statistical analysis was done using chi square test and student's t-test.

   Results Top

There were nine patients in the affected group, all of whom were males. Their mean age was 44 ± 9 years. The primary renal disease was chronic glomerulonephritis (CGN) in seven cases, and focal and segmental glomerulo­sclerosis (FSGS) and autosomal dominant polycyctic kidney disease (ADPKD) in one case each. All patients were non-smokers. Immunosuppressive therapy prescribed was standard doses of cyclosporin, prednisolone and azathioprin in seven patients and cyclosporin and prednisolone in the two remaining patients. All patients were hypertensive; eight were managed with beta-blockers and calcium channel blockers and one patient was on ACE­I. Two patients developed post-transplant diabetes mellitus. PTE developed 1-60 months (9.8 ± 9 months) post-kidney transplantation, and lasted for an average of 37.3 ± 3 months (range 9 - 84 months) [Table - 1]. Remission of PTE was seen in all patients. All patients were treated with phlebotomies except one who was given ACE-I. Complications in the form of deep vein thrombosis (DVT) of lower limbs occurred in only one patient. Average level of hemoglobin (Hb) and HCT at the onset of PTE was 18 ± 1 g/dL and 54 ± 10% respectively. Hematocrit was maintained below 55% in all patients with phlebotomies and ACE-I. Four of the nine patients (44%) developed chronic rejection, and their mean serum creatinine level at the end of their follow­up period was 150.28 ± 79.56 µmol/L [Table - 2].

In the second group, there were 38 patients (30 male and 8 female). Their mean age was 40 ± 11 years, and mean follow-up period was 93 ± 58 months [Table - 3]. The primary renal disease was CGN in 28 cases, ADPKD, diabetic nephropathy and Alport's syndrome in one patient each, and in five cases the etiology was unknown. Thirty three patients were hypertensive and seven were diabetic, and all but seven were non-smokers. The prescribed immunosuppressive regimens and antihypertensive medications are shown in [Table - 3]. Their average levels of Hb and HCT at the end of the follow-up period were 12.4 g/dl and 37.3 % respectively. The average serum creatinine at the end of follow-up was 114.92 µmol/L, and four of the 38 patients (11%) in this group developed chronic rejection.

   Discussion Top

PTE occurred in nine out of the 47 patients studied, indicating a prevalence of 19%, which is close to the reported prevalence of 5-17%. [1],[2] All the patients who developed PTE were males, confirming findings in other studies that PTE is more common in males. [12] The mean onset of PTE in this study was 9.8 ± 9 months (range 1- 60 months) follo­wing kidney transplantation, compared with an avera~e of 24 months reported in other series. [1] This illustrates the need of close observation of RTR for the development of PTE, particularly in the initial few years following renal transplantation.

The duration of PTE in this study was 37.3 ± 3 months (range 9 - 84 months), compared with longer periods reported in other series. [3],[4] One patient in this study who had PTE for 84 months (patient no. 5), maintained normal graft function until the end of the follow-up period. He had no thromboembolic compli­cations and was managed with phlebotomies. This demonstrates that PTE may occur in its severe form in patients with good graft function, as has been shown in other studies as well. [12] Over all, the course of PTE in this series was quite protracted.

The etiology of PTE is poorly understood, and it is probably multifactorial. Many of these patients have contracted plasma volume due to uncontrolled hypertension, diabetes mellitus and use of diuretics. [12] However, when these factors are excluded, the true prevalence of PTE is found to be 5-10% only. [7],[13],[14] In this

study, the above factors were not relevant since patients with diabetes mellitus and hypertension had good control of the blood sugar and blood pressure respectively. Further­more, overproduction of erythropoietin [5] or exaggerated response of the bone marrow to EPO may play a pivotal role. [12] EPO levels were not measured in this study, but other studies have shown that EPO levels can be high or within normal limits. [14],[15]

A number of factors have been suggested to provoke over-production of EPO by the transplanted kidney. [12],[16],[17] These include cyclosporin, chronic rejection, renal artery stenosis and hydronephrosis of the trans­planted kidney, which is known to induce renal ischemia and thus increase EPO production. PTE has been found to be more common in patients treated with cyclosporin than those on azathioprin and prednisolone. [18] In this series, all the patients were on cyclosporin. Chronic rejection has also been proposed as a factor causing ischemia and EPO over­production. [12] In this series, 44% of patients with PTE had chronic rejection, while only 11% of patients without PTE developed this complication. The difference in the prevalence of chronic rejection in the two groups was significant [Table - 4]. Thus, chronic rejection may be an important predisposing factor for PTE. However, PTE has been reported to occur in its most aggressive form in patients with excellent allograft function. [13] It is possible that chronic rejection may complicate long standing PTE, as noticed in this study, and hence PTE may represent a marker for future chronic rejections. Renal artery stenosis has been shown to cause PTE by producing renal ischemia and over-production of EPO by the transplanted kidney. [19] However, no evidence of this has been seen in this series. [13] Hydronephrosis of the transplanted kidney is known to induce renal ischemia [12],[16],[17] and may result in PTE. This complication occurred in one patient (patient number 2) during the first year of post-transplant period, and was caused by a urethral stricture. Native kidne6ys, which are known to be a source of EPO may contribute to the development of PTE. This was noticed in patient number 2, whose original renal disease was ADPKD. It is also possible that combination of some or all of these factors may lead to the patho­genesis of PTE, as was seen in patient number 2 who suffered from ADPKD, hydronephrosis of the transplanted kidney, chronic rejection, hypertension, diabetes mellitus and the use of diuretics. However, five of our patients with PTE had no apparent predisposing factors [Table - 1]. This shows that PTE may result from over-aggressive response of bone marrow to EPO alone.

Most patients were easily controlled with repeated phlebotomies (8 out of 9 patients). Recently, ACE inhibitors have become a standard form of therapy for PTE. [10],[16],[20] The mechanism of these drugs in improving PTE is not well understood. However, they have been shown to be safe and effective. In this series, one patient (number 9) was treated with captopril and responded well. Eventually, all our patients had complete remission, despite the variability in duration. This was not diffe­rent from what has been reported in other studies. [21]

Thromboembolic complications are well known to occur in patients with PTE. In this study, only one patient (number 9) developed deep vein thrombosis in the right lower limb. This might have been related to rebound in­crease in hematocrit to 58% resulting from the temporary discontinuation of captopril because of the development of cough. How­ever, this patient recovered following com­mencement of anticoagulation and resumption of captopril therapy [Table - 1]. In general, our study showed that PTE was quite benign and free of complications despite its protracted course in some patients.

   Conclusion Top

Our study shows that PTE is a relatively common complication after kidney transplan­tation. It usually appears in the first year of transplantation, although it may have a delayed onset. PTE is more common in males. It may last for a variable period (up to 84 months), but eventually undergoes remission. The etiology of PTE is multifactorial which may colle­ctively operate at the same time and in the same patient. PTE can occur in a severe form in patients with good graft function, although at a later stage, chronic rejection may occur more commonly in these patients. Thrombo­embolic complications are rare, but can occur if hematocrit rises above 55%. PTE can be easily controlled by serial phlebotomies, but ACE inhibitors are equally effective. Finally, the course of PTE is mostly quite benign.

   References Top

1.Perazella MA, Bia MJ. Posttransplant erythrocytosis. Case report and review of the newer treatment modalities. J Am Soc Nephrol 1993;3:1653-9.  Back to cited text no. 1    
2.Gaston RS, Julian BA, Curtis JJ. Posttransplant erythrocytosis an enigma revisited. Am J Kidney Dis 1994;24:1-11.  Back to cited text no. 2  [PUBMED]  
3.Innes A, Pal CR, Dennis MJ, Ryan JJ, Morgan AG, Burden RP. Post-transplant erythrocytosis and immunosuppression with cyclosporin: a case control study. Nephrol Dial Transplant 1991;6:588-91.  Back to cited text no. 3    
4.Wickre CG, Norman DJ, Bennison A, Barry JM, Bennett WM. Postrenal transplant erythrocytosis: a review of 53 patients. Kidney Int 1983;23:731-7.  Back to cited text no. 4  [PUBMED]  
5.Glicklich D, Kapoian T, Mian H, Gilman J, Tellis V, Croizat H. Effects of erythropoietin, angiotensin II, and angiotensin - converting enzyme inhibitor on erythroid precursors in patients with post-transplantation erythro­cytosis. Transplantation 1999;68(1):62-6.  Back to cited text no. 5    
6.Friman S, Nyberg G, Blohme l. Erythro­cytosis after renal transplantation: treatment by removal of the native kidneys. Nephrol Dial Transplant 1990;5:969-73.  Back to cited text no. 6    
7.Bakris GL, Sauter ER, Hussey JL, et al. Effects of theophylline on erythropoietin production in normal subjects and in patients with erythrocytosis after renal transplantation. N Engl J Med 1990;323:86-90.  Back to cited text no. 7  [PUBMED]  
8.Islam MS, Bourbigot B, Codet JP, Songy B, Fournier G, Cledes J. Captopril induces correction of postrenal transplant erythremia. Transplant Int 1990;3:222-5.  Back to cited text no. 8    
9.Danovitch GM, Jamgotchian NJ, Eggena PH, et al. Angiotensin - converting enzyme inhibition in the treatment of renal transplant erythrocytosis. Clinical experience and observation of mechanism. Transplantation 1995;60:132-7.  Back to cited text no. 9    
10.Marubayashi S, Yamamoto H, Shibata S, et al. Effect of the angiotensin - converting enzyme inhibitor on post transplant erythro­cytosis. Hiroshima J Med Sci1998; 47(3):121-4.  Back to cited text no. 10    
11.Montanaro D, Groupuzzo M, Boscutti G, Risaliti A, Bresadola F, Mini G. Long-term therapy for post renal transplant erythro­cytosis with ACE inhibitors: efficacy, safety and action mechanisms. Clin Nephrol 2000; 53(4):47-51.  Back to cited text no. 11    
12.Kessler M, Hestin D, Mayeux D, Mertes PM, Renoult E. Factors predisposing to post renal transplant erythrocytosis. A prospective matched - pair control study. Clin Nephrol 1996;25(2):83-9.  Back to cited text no. 12    
13.Qunibi WY, Barri Y, Devol E, Al - Furayh O, Sheth K, Taher S. Factors predictive of post - transplant erythrocytosis. Kidney Int 1990;40:1153-9.  Back to cited text no. 13    
14.Perazella M, McPhedran P, Kliger A, Lorber M, Levy E, Bia MJ. Enalapril treatment of posttransplant erythrocytosis: Efficacy independent of circulating erythro­poietin levels. Am J Kidney Dis 1995;26: 495-500.  Back to cited text no. 14  [PUBMED]  
15.Lezaic V, Djukanovic LJ, Pavlovic-Kentera V, Clemons G, Biljanovic-Paunovic L. Factors including post transplant erythrocytosis. Eur J Med Res 1997;2(9): 407-12.  Back to cited text no. 15    
16.Mirand EA, Murphy GP. Erythropoietin alterations in patients with uremia, renal allografts or without kidneys. JAMA 1969: 209:392-8.  Back to cited text no. 16    
17.Dagher FJ, Ramos E, Erslev AJ, et al. Are the native kidneys responsible for erythro­cytosis in renal allorecipients. Transplantation 1979;28:496-8.  Back to cited text no. 17  [PUBMED]  
18.Gruber SA, Simmons RL, Najarian JS, et al. Post transplant erythrocytosis and the risk of thromboembolic complications: correlation from a prospective randomized study of cyclosporine versus azathioprine - anti lymphocytes globulin. Clin Transplant 1988;2:60-6.  Back to cited text no. 18    
19.Bacon BR, Rothman SA, Ricanati ES, Rashad FA. Renal artery stenosis with erythrocytosis after renal transplantation. Arch Intern Med 1980;140:1206-11.  Back to cited text no. 19  [PUBMED]  
20.Gossmann J, Thurmann P , BachmannT, et al. Mechanism of angiotensin converting enzyme inhibitor - related anemia in renal transplant recipients. Kidney Int 1996;50: 973-8.  Back to cited text no. 20    
21.Gaston RS, Julian BA, Barker CV, Diethelm AG, Curtis JJ. Enalapril: safe and effective therapy for posttransplant erythro­cytosis. Transplant Proc 1993;25:1029-31.  Back to cited text no. 21  [PUBMED]  

Correspondence Address:
Mohamed Abdelrahman
Department of Nephrology, Dammam Central Hospital, P.O. Box 10387, Dammam 31433
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

PMID: 17642778

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