Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Erythrocytosis following renal transplantation

Daniel C Brennan, MD, FACP
Demetrios V Vlahakos, MD
Section Editor
Barbara Murphy, MB, BAO, BCh, FRCPI
Deputy Editor
Albert Q Lam, MD


Posttransplant erythrocytosis (PTE) occurs in 8 to 15 percent of renal transplant recipients and usually affects patients with well-preserved graft function [1-4]. The pathogenesis and treatment of this disorder is reviewed here. An overview of the general approach to the patient with polycythemia is presented separately. (See "Diagnostic approach to the patient with polycythemia".)


Posttransplant erythrocytosis (PTE) is defined as persistently elevated hemoglobin and hematocrit levels that occur following renal transplantation and persist for more than six months in the absence of thrombocytosis, leukocytosis, or another potential cause of erythrocytosis [1-5].

The threshold hematocrit used to define PTE is variable and ranges between 51 to 54 percent; most clinicians use 51 percent (corresponding to a hemoglobin concentration of approximately 17 g/dL) [2,6-14].

PTE occurs in 8 to 15 percent of renal transplant recipients; a few studies have reported incidences as high as 22 percent [1-5,15]. The disparity in reported prevalence is due in part to the variably defined hematocrit thresholds used and the inclusion of transitory erythrocytosis (ie, persisting for less than six months) [2]. Differences in immunosuppressive regimens may also contribute to disparities between centers in the reported prevalence of PTE since individual agents have variable effects on hemoglobin.

The incidence of PTE appears to be decreasing. Erythrocytosis defined as hemoglobin >17 g/dL was reported in 19 percent of those transplanted between 1993 to 1996, but only 8 percent of those transplanted between 1997 to 2005 [4].


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Jan 27, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Gaston RS, Julian BA, Curtis JJ. Posttransplant erythrocytosis: an enigma revisited. Am J Kidney Dis 1994; 24:1.
  2. Vlahakos DV, Marathias KP, Agroyannis B, Madias NE. Posttransplant erythrocytosis. Kidney Int 2003; 63:1187.
  3. Augustine JJ, Knauss TC, Schulak JA, et al. Comparative effects of sirolimus and mycophenolate mofetil on erythropoiesis in kidney transplant patients. Am J Transplant 2004; 4:2001.
  4. Kiberd BA. Post-transplant erythrocytosis: a disappearing phenomenon? Clin Transplant 2009; 23:800.
  5. Einollahi B, Lessan-Pezeshki M, Nafar M, et al. Erythrocytosis after renal transplantation: review of 101 cases. Transplant Proc 2005; 37:3101.
  6. Wickre CG, Norman DJ, Bennison A, et al. Postrenal transplant erythrocytosis: a review of 53 patients. Kidney Int 1983; 23:731.
  7. 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.
  8. Morrone LF, Di Paolo S, Logoluso F, et al. Interference of angiotensin-converting enzyme inhibitors on erythropoiesis in kidney transplant recipients: role of growth factors and cytokines. Transplantation 1997; 64:913.
  9. Torregrosa JV, Campistol JM, Montesinos M, et al. Efficacy of captopril on posttransplant erythrocytosis. Long-term follow-up. Transplantation 1994; 58:311.
  10. Conlon PJ, Farrell J, Donohoe J, Walshe JJ. The beneficial effect of enalapril on erythrocytosis after renal transplantation. Transplantation 1993; 56:217.
  11. Lal SM, Trivedi HS, Ross G Jr. Long term effects of ACE inhibitors on the erythrocytosis in renal transplant recipients. Int J Artif Organs 1995; 18:13.
  12. Thevenod F, Radtke HW, Grützmacher P, et al. Deficient feedback regulation of erythropoiesis in kidney transplant patients with polycythemia. Kidney Int 1983; 24:227.
  13. Dagher FJ, Ramos E, Erslev A, et al. Erythrocytosis after renal allotransplantation: treatment by removal of the native kidneys. South Med J 1980; 73:940.
  14. Hernández E, Morales JM, Andrés A, et al. Usefulness and safety of treatment with captopril in posttransplant erythrocytosis. Transplant Proc 1995; 27:2239.
  15. Kessler M, Hestin D, Mayeux D, et al. Factors predisposing to post-renal transplant erythrocytosis. A prospective matched-pair control study. Clin Nephrol 1996; 45:83.
  16. Qunibi WY, Barri Y, Devol E, et al. Factors predictive of post-transplant erythrocytosis. Kidney Int 1991; 40:1153.
  17. Razeghi E, Kaboli A, Pezeshki ML, et al. Risk factors of erythrocytosis post renal transplantation. Saudi J Kidney Dis Transpl 2008; 19:559.
  18. Dagher FJ, Ramos E, Erslev AJ, et al. Are the native kidneys responsible for erythrocytosis in renal allorecipients? Transplantation 1979; 28:496.
  19. Julian BA, Brantley RR Jr, Barker CV, et al. Losartan, an angiotensin II type 1 receptor antagonist, lowers hematocrit in posttransplant erythrocytosis. J Am Soc Nephrol 1998; 9:1104.
  20. Frei D, Guttmann RD, Gorman P. A matched-pair control study of postrenal transplant polycythemia. Am J Kidney Dis 1982; 2:36.
  21. Gaston RS, Julian BA, Diethelm AG, Curtis JJ. Effects of enalapril on erythrocytosis after renal transplantation. Ann Intern Med 1991; 115:954.
  22. Schramek A, Better OS, Adler O, et al. Hypertensive crisis, erythrocytosis, and uraemia due to renal-artery stenosis of kidney transplants. Lancet 1975; 1:70.
  23. Bacon BR, Rothman SA, Ricanati ES, Rashad FA. Renal artery stenosis with erythrocytosis after renal transplantation. Arch Intern Med 1980; 140:1206.
  24. Guerra G, Indahyung R, Bucci CM, et al. Elevated incidence of posttransplant erythrocytosis after simultaneous pancreas kidney transplantation. Am J Transplant 2010; 10:938.
  25. Aeberhard JM, Schneider PA, Vallotton MB, et al. Multiple site estimates of erythropoietin and renin in polycythemic kidney transplant patients. Transplantation 1990; 50:613.
  26. Ilan Y, Dranitzki-Elhallel M, Rubinger D, et al. Erythrocytosis after renal transplantation. The response to theophylline treatment. Transplantation 1994; 57:661.
  27. Kiykim AA, Genctoy G, Horoz M, et al. Serum stem cell factor level in renal transplant recipients with posttransplant erythrocytosis. Artif Organs 2009; 33:1086.
  28. Brox AG, Mangel J, Hanley JA, et al. Erythrocytosis after renal transplantation represents an abnormality of insulin-like growth factor-I and its binding proteins. Transplantation 1998; 66:1053.
  29. Kirshenbaum AS, Goff JP, Kessler SW, et al. Effect of IL-3 and stem cell factor on the appearance of human basophils and mast cells from CD34+ pluripotent progenitor cells. J Immunol 1992; 148:772.
  30. Lamperi S, Carozzi S. Erythroid progenitor growth in erythrocytosic transplanted patients. Artif Organs 1985; 9:200.
  31. Vlahakos DV, Marathias KP, Madias NE. The role of the renin-angiotensin system in the regulation of erythropoiesis. Am J Kidney Dis 2010; 56:558.
  32. Gossmann J, Burkhardt R, Harder S, et al. Angiotensin II infusion increases plasma erythropoietin levels via an angiotensin II type 1 receptor-dependent pathway. Kidney Int 2001; 60:83.
  33. Mrug M, Stopka T, Julian BA, et al. Angiotensin II stimulates proliferation of normal early erythroid progenitors. J Clin Invest 1997; 100:2310.
  34. Glicklich D, Kapoian T, Mian H, et al. Effects of erythropoietin, angiotensin II, and angiotensin-converting enzyme inhibitor on erythroid precursors in patients with posttransplantation erythrocytosis. Transplantation 1999; 68:62.
  35. Azizi M, Rousseau A, Ezan E, et al. Acute angiotensin-converting enzyme inhibition increases the plasma level of the natural stem cell regulator N-acetyl-seryl-aspartyl-lysyl-proline. J Clin Invest 1996; 97:839.
  36. Azizi M, Ezan E, Nicolet L, et al. High plasma level of N-acetyl-seryl-aspartyl-lysyl-proline: a new marker of chronic angiotensin-converting enzyme inhibition. Hypertension 1997; 30:1015.
  37. Cole J, Ertoy D, Lin H, et al. Lack of angiotensin II-facilitated erythropoiesis causes anemia in angiotensin-converting enzyme-deficient mice. J Clin Invest 2000; 106:1391.
  38. Glicklich D, Burris L, Urban A, et al. Angiotensin-converting enzyme inhibition induces apoptosis in erythroid precursors and affects insulin-like growth factor-1 in posttransplantation erythrocytosis. J Am Soc Nephrol 2001; 12:1958.
  39. Shih LY, Huang JY, Lee CT. Insulin-like growth factor I plays a role in regulating erythropoiesis in patients with end-stage renal disease and erythrocytosis. J Am Soc Nephrol 1999; 10:315.
  40. Kedzierska K, Kabat-Koperska J, Safranow K, et al. Influence of angiotensin I-converting enzyme polymorphism on development of post-transplant erythrocytosis in renal graft recipients. Clin Transplant 2008; 22:156.
  41. Richard DE, Berra E, Pouyssegur J. Nonhypoxic pathway mediates the induction of hypoxia-inducible factor 1alpha in vascular smooth muscle cells. J Biol Chem 2000; 275:26765.
  42. Kujawa-Szewieczek A, Kolonko A, Kocierz M, et al. Association between gene polymorphisms of the components of the renin-angiotensin-aldosteron system, graft function, and the prevalence of hypertension, anemia, and erythrocytosis after kidney transplantation. Transplant Proc 2011; 43:2957.
  43. Kato H, Ishida J, Matsusaka T, et al. Erythropoiesis and Blood Pressure Are Regulated via AT1 Receptor by Distinctive Pathways. PLoS One 2015; 10:e0129484.
  44. Remynse LC, Begun FP, Jacobs SC, Lawson RK. Juxtaglomerular cell tumor with elevation of serum erythropoietin. J Urol 1989; 142:1560.
  45. Erkelens DW, Statius van Eps LW. Bartter's syndrome and erythrocytosis. Am J Med 1973; 55:711.
  46. Vlahakos DV, Canzanello VJ, Madaio MP, Madias NE. Enalapril-associated anemia in renal transplant recipients treated for hypertension. Am J Kidney Dis 1991; 17:199.
  47. Cross NB, Webster AC, Masson P, et al. Antihypertensive treatment for kidney transplant recipients. Cochrane Database Syst Rev 2009; :CD003598.
  48. Vlahakos DV, Marathias KP, Kosmas EN. Losartan reduces hematocrit in patients with chronic obstructive pulmonary disease and secondary erythrocytosis. Ann Intern Med 2001; 134:426.
  49. Plata R, Cornejo A, Arratia C, et al. Angiotensin-converting-enzyme inhibition therapy in altitude polycythaemia: a prospective randomised trial. Lancet 2002; 359:663.
  50. Herrlin B, Nyquist O, Sylvén C. Induction of a reduction in haemoglobin concentration by enalapril in stable, moderate heart failure: a double blind study. Br Heart J 1991; 66:199.
  51. Ishani A, Weinhandl E, Zhao Z, et al. Angiotensin-converting enzyme inhibitor as a risk factor for the development of anemia, and the impact of incident anemia on mortality in patients with left ventricular dysfunction. J Am Coll Cardiol 2005; 45:391.
  52. Odabas AR, Cetinkaya R, Selcuk Y, et al. The effect of high dose losartan on erythropoietin resistance in patients undergoing haemodialysis. Panminerva Med 2003; 45:59.
  53. Ertürk S, Nergizoğlu G, Ateş K, et al. The impact of withdrawing ACE inhibitors on erythropoietin responsiveness and left ventricular hypertrophy in haemodialysis patients. Nephrol Dial Transplant 1999; 14:1912.
  54. Le Meur Y, Lorgeot V, Comte L, et al. Plasma levels and metabolism of AcSDKP in patients with chronic renal failure: relationship with erythropoietin requirements. Am J Kidney Dis 2001; 38:510.
  55. Rell K, Koziak K, Jarzyo I, et al. Correction of posttransplant erythrocytosis with enalapril. Transplantation 1994; 57:1059.
  56. Perazella M, McPhedran P, Kliger A, et al. Enalapril treatment of posttransplant erythrocytosis: efficacy independent of circulating erythropoietin levels. Am J Kidney Dis 1995; 26:495.
  57. Julian BA, Gaston RS, Barker CV, et al. Erythropoiesis after withdrawal of enalapril in post-transplant erythrocytosis. Kidney Int 1994; 46:1397.
  58. Gross M, Goldwasser E. On the mechanism of erythropoietin-induced differentiation. XIV. The apparent effect of etiocholanolone on initiation of erythropoiesis. Exp Hematol 1976; 4:227.
  59. Zanjani ED, Banisadre M. Hormonal stimulation of erythropoietin production and erythropoiesis in anephric sheep fetuses. J Clin Invest 1979; 64:1181.
  60. Nielsen AH, Johannessen A, Poulsen K. Inactive plasma renin exhibits sex difference in mice. Clin Sci (Lond) 1989; 76:439.
  61. Maktouf C, Yaich S, Aloui S, et al. Angiogenic activity in the sera of patients with post-kidney transplant erythrocytosis. Saudi J Kidney Dis Transpl 2014; 25:1026.
  62. Ok E, Akçiçek F, Töz H, et al. Comparison of the effects of enalapril and theophylline on polycythemia after renal transplantation. Transplantation 1995; 59:1623.
  63. Montanaro D, Groupuzzo M, Boscutti G, et al. Long-term therapy for postrenal transplant erythrocytosis with ACE inhibitors: efficacy, safety and action mechanisms. Clin Nephrol 2000; 53:suppl 47.
  64. Yildiz A, Cine N, Akkaya V, et al. Comparison of the effects of enalapril and losartan on posttransplantation erythrocytosis in renal transplant recipients: prospective randomized study. Transplantation 2001; 72:542.
  65. Klaassen RJ, van Gelder T, Rischen-Vos J, et al. Losartan, an angiotensin-II receptor antagonist, reduces hematocrits in kidney transplant recipients with posttransplant erythrocytosis. Transplantation 1997; 64:780.
  66. Midtvedt K, Stokke ES, Hartmann A. Successful long-term treatment of post-transplant erythrocytosis with losartan. Nephrol Dial Transplant 1996; 11:2495.
  67. Hiremath S, Fergusson D, Doucette S, et al. Renin angiotensin system blockade in kidney transplantation: a systematic review of the evidence. Am J Transplant 2007; 7:2350.
  68. Gossmann J, Thürmann P, Bachmann T, et al. Mechanism of angiotensin converting enzyme inhibitor-related anemia in renal transplant recipients. Kidney Int 1996; 50:973.
  69. MacGregor MS, Rowe PA, Watson MA, et al. Treatment of postrenal transplant erythrocytosis. Long-term efficacy and safety of angiotensin-converting enzyme inhibitors. Nephron 1996; 74:517.
  70. Ducloux D, Fournier V, Bresson-Vautrin C, Chalopin JM. Long-term follow-up of renal transplant recipients treated with losartan for post-transplant erythrosis. Transpl Int 1998; 11:312.
  71. Barenbrock M, Spieker C, Rahn KH, Zidek W. Therapeutic efficiency of phlebotomy in posttransplant hypertension associated with erythrocytosis. Clin Nephrol 1993; 40:241.
  72. 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.
  73. Mazzali M, Filho GA. Use of aminophylline and enalapril in posttransplant polycythemia. Transplantation 1998; 65:1461.
  74. Borawski J, Mazerska M, Rydzewski A, et al. Ketanserin: a new perspective in posttransplant erythrocytosis? Clin Transplant 1996; 10:63.