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Saudi Journal of Kidney Diseases and Transplantation
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Year : 1998  |  Volume : 9  |  Issue : 2  |  Page : 144-146
Treatment of Post-transplant Erythrocytosis with Enalapril

Department of Nephrology, King Hussein Medical Center, Amman, Jordan

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This prospective study was carried out to estimate the efficacy and safety of Enalapril therapy in post-transplant erythrocytosis. Thirteen long-term renal allograft recipients (11 males and two females) with increased hematocrit values (>51%) and elevated red cell mass were treated with Enalapril for 12 weeks; their age ranged from 18 to 54 years. At the end of the study period the mean hematocrit values decreased from 53.9% to 46.7%, red cell mass significantly decreased from 50.8 ml/kg to 40.5 ml/kg. During the following six months without Enalapril treatment, an increase in hematocrit was observed reaching a mean of 47.5%. In conclusion, enalapril can be safely and efficiently used to treat post-transplant erythrocytosis.

How to cite this article:
Akash N, Smadi I, El-Lozi M. Treatment of Post-transplant Erythrocytosis with Enalapril. Saudi J Kidney Dis Transpl 1998;9:144-6

How to cite this URL:
Akash N, Smadi I, El-Lozi M. Treatment of Post-transplant Erythrocytosis with Enalapril. Saudi J Kidney Dis Transpl [serial online] 1998 [cited 2021 Apr 15];9:144-6. Available from: https://www.sjkdt.org/text.asp?1998/9/2/144/39287

   Introduction Top

Post-transplant erythrocytosis defined as a persistently elevated hematocrit (> 51%), is a well recognized but poorly understood complication of renal transplantation [1],[2] . It occurs most commonly in the first year post-transplantation. The consequences are disputed but may include increased risk of thrombo-embolic events. Post-transplant erythrocytosis has been thought to reflect excess erythropoietin production from either native kidneys or allograft and tends to abate spontaneously with time [3] . More recent data dispute such a contention and suggest that spontaneous remission is relatively uncommon [4],[5] .

Since it has been reported that enalapril may induce anemia in renal allograft recipients [6],[16] , we have undertaken a prospective study to estimate the efficacy and safety of Enalapril therapy on post­-transplant erythrocytosis.

   Materials and Methods Top

We studied 13 long term (> 6 months) renal allograft recipients with increased hematocrit (>51%). They were 11 males and two females with age ranging from 18 to 54 years. The cause of renal failure was glomerulonephritis in ten and diabetes mellitus in three. The interval between transplantation and appearance of erythrocytosis ranged from seven to 20 months. The average hematocrit (Hct) before transplantation was 27%. Nine patients were on prednisolone, cyclosporine, and azathioprine, while four were only on prednisolone and azathioprine as post­transplant immumnosuppressive therapy.

To evaluate possible causes of post-transplant erythrocytosis each patient underwent a thorough investigations including the following;

  1. Measurement of saturation
  2. of hemoglobin in the arterial blood.
  3. Pulmonary function tests.
  4. Liver function tests.

The results did not reveal any cause of secondary erythrocytosis. hi all patients renal artery stenosis was excluded by means of normal Doppler ultrasound. Patients enrolled in this study had stable renal function tests and well controlled blood pressure (BP).

The following data were collected before the study and then on every outpatient visit: B.P, Hct, hemoglobin, complete blood count, ferritin and creatinine levels.

Diuretics were temporarily withdrawn before the treatment with Enalapril. After the initial dose of enalapril (2.5 mg), subsequent doses were gradually increased over a period of four weeks. The recipients continued to take enalapril for 12 consecutive weeks, then it was stopped and patients were followed up for three months.

   Results Top

All patients had true erythrocytosis as defined by increases red cell mass and hematocrit and absence of known causes of secondary erythrocytosis.

After 12 weeks of therapy with enalapril the study group had significant decline in the mean hematocrit values from 53.9% to 46.7%, which remained significantly low through the entire period of enalapril treatment. The average red cell mass decreased from 50,8 ml/kg to 40.5 ml/kg.

After discontinuation of enalapril therapy, an increase in hematocrit was noted reaching a mean of 47.5% due to rapid rebound of hematocrit, two of the 13 patients required re-­administration of enalapril. No serious side effects of enalapril were observed. Renal function did not change in recipients treated with enalapril. In seven patients, other anti­-hypertensives were withdrawn, or their doses were tapered off during the study period.

   Discussion Top

Erythrocytosis is a well-known complication of renal transplantation. It was first described more than 20 years ago and since then more reports have been published [7],[8] . It is estimated to affect 10 to 20% of renal transplant recipients [2],[9] . There is an increased incidence of thrombotic events including phlebitis, cerebro-vascular accidents, and pulmonary embolism, which have been observed in some studies [2],[10] . There are several predisposing factors to erythrocytosis including acute or chronic allograft rejection, renal artery stenosis, hydronephrosis, cyclos­porine A therapy and the original renal disease [9],[11],[12],[13] . Increased level of erythropoietin and increased sensitivity of erythroid colony forming units (CFU) to erythropoietin have been suggested as possible mechanisms [14] .

Administration of enalapril to renal allograft recipients with erythrocytosis results in a significant decrease in hematocrit and red blood cell mass [6],[15] . Our results support previous reports that angiotensin converting enzyme inhibitors (ACEIs) can normalize hematocrit in renal graft recipients with erythrocytosis. Enalapril treatment eliminated the need for phlebotomies in our patients.

However, there is a general agreement that enalapril and other ACEIs should be used with great caution in kidney transplant patients, as renal artery stenosis may be present with a possibility of acute renal failure developing upon administration of ACEIs [6],[16] .

It is not fully clear how erythropoietin is modulated by the renin angiotensin system. It may act by improving renal and/or hepatic blood flow and thus preventing hypoxemia induced erythropoietin production [17] . Other possible mechanisms include inhibition of erythropoietin effect on stem cells or increased level of bradykinin formed during blockade of kinin degradation [17] .

Alternative therapies for post-transplant erythrocytosis include native kidney neph­rectomy, repeated phlebotomies and theo­phylline administration but they have not been widely accepted.

In conclusion, several mechanisms may be involved in the pathogenesis of erythrocytosis after kidney transplantation; enalapril can lower hematocrit and should probably be tried in all patients with post-transplant erythrocytosis after excluding the presence of renal artery stenosis.

   References Top

1.Gaston RS, Julian BA, Curtis JJ. Post transplant erythrocytosis: an enigma revisited. Am J Kidney Dis 1994;24:1-11.  Back to cited text no. 1  [PUBMED]  
2.Wickre CG, Norman DJ, Bennison A, Barry JM, Bennett WM. Post renal transplant erythrocytosis: a review of 53 patients. Kidney Int 1983;23:731-7.  Back to cited text no. 2  [PUBMED]  
3.Chan L, Kam I, Spees EK. Outcome and complications of renal transplantation, in Schricr RW, Gottschalk CW (ed): Diseases of the kidneys, Boston MA Little, Brown 1993;2911-67.  Back to cited text no. 3    
4.Ramos EL, Balagtas R. Posttransplant erythrocytosis. J Nephrol 1992,S9-13.  Back to cited text no. 4    
5.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. 5    
6.Rell K; Koziak K, Jarzyo I, Lao M, Gaciong Z. Correction of posttransplant erythrocytosis with enalapril. Transplantation 1994;57:1059-63.  Back to cited text no. 6    
7.Nies BA, Cohn R, Schrier SL. Erythremia after renal transplantation. N Eng J Med 1982;273-75.  Back to cited text no. 7    
8.Swales JD. Evans DB. Erythraemia in renal transplantation. Br Med J 1969;2:80-3.  Back to cited text no. 8    
9.Nellans R, Otis P, Martin DC. Polycythemia following renal transplantation. Urology 1975;6:158- 63.  Back to cited text no. 9  [PUBMED]  
10.Grubner SA, Simmons RL, Najarian JS, et al. Post-transplant erythorocytosis and the risk of thromboembolic complications. Clin Transpl 1988;2:60.  Back to cited text no. 10    
11.Sumrani NB, Daskalakis P, Miles AM, et al. Erythrocytosis after renal transplantation. A prospective analysis. ASAIO J 1993;39:51-5.  Back to cited text no. 11    
12.Hammond D, Winnick S. Paraneoplastic erythrocytosis and ectopic erythropoietins. Ann NY Acad Sci 1974;230:219-27.  Back to cited text no. 12  [PUBMED]  
13.Stockenhuber F, Geissler K, Balki P, et al. Polyglobulin in renal allograft recipients due to direct effect of CyA (abstract). Kidney Int 1988;33:452.  Back to cited text no. 13    
14.Ogawa M. Erythroid progenitors in Gold D (ed). Methods in hematology and hemato-poeisis; New York Churchill Livingstone 1989:123.  Back to cited text no. 14    
15.Rostaing L, Boisseau M, Durand D. Huyn A, Lloveras JJ, Sue JM. Successful treatment of post-renal transplant erythrocytosis with Enalapril. Transplant Proc 1993;25:2325-6.  Back to cited text no. 15    
16.Ahmad T, Coulthard MG, Eastham EJ. Reversible renal failure due to the use of captopril in a renal allograft recipient treated with cyclosporin. Nephrol Dial Transplant 1989;4:311-2.  Back to cited text no. 16  [PUBMED]  [FULLTEXT]
17.Perazella MA, Bia MJ. Posttransplant erythrocytosis: case report and review of newer treatment modalities. J Am Soc Nephroll993;3:1653-9.  Back to cited text no. 17    

Correspondence Address:
N Akash
Department of Nephrology, King Hussein Medical Center, P.O. Box 960955, Amman 11196, Amman
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PMID: 18408290

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