Clinical characteristics and treatment of six kidney recipients with human parvovirus B19 infection_West China Medical Journal

Authors：

GAO Peijuan , SHI Yunying , PU Wenshen ,  TAO Ye

Department of Nephrology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

TAO Ye, Email: yehtao11@163.com

Keywords：

Renal transplantation; Human parvovirus B19; Pure red cell aplasia; Intravenous immunoglobulin; Immunosupressants

DOI：

10.7507/1002-0179.201905234

Video：

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Objective To investigate the diagnosis, clinical features, treatment and outcome of pure red cell aplasia (PRCA) caused by human parvovirus B19 (HPV-B19) infection in kidney recipients. Method The clinical courses of six patients with PRCA caused by HPV-B19 infection after renal transplantation in West China Hospital between May 2018 and April 2019 were retrospectively investigated. Results The six patients showed obvious anemia symptoms, lacking rash, joint pain and other clinical symptoms of viral infection. The hemoglobin level of five patients got totally remission from a course of intravenous immunoglobulin (IVIG) treatment, and anemia symptoms like fatigue, weakness got notable improvement. One patient had no improvement after two courses of IVIG treatment, and his anemia was significantly improved after the third IVIG course combined with immunosuppressant conversion(from tacrolimus to cyclosporine), and one patient with recurrence accepted a repeated course of IVIG treatment and obtained remission of severe anemia again. The median time of reticulocyte firstly rose to above 0.084×10¹²/L from the day of IVIG treatment ended was 3.50 (1.25, 5.00) days, and the median time required for a 30 g/L increase in hemoglobin to the end of IVIG treatment was 16.00 (9.25, 31.25) days. No serious adverse reactions occurred and all patients had stable graft function. Conclusions The main clinical manifestations of PRCA caused by HPV-B19 infection after kidney transplantation are anemia symptoms, lacking other clinical symptoms of viral infection. HPV-B19 DNA detection combined with blood routine examination, reticulocyte count and bone marrow cytology (or none) can diagnose HPV-B19 infection. High dose of IVIG is effective and safe, and a repeated course is still effective when the infection recurs. For refractory PRCA that IVIG monotherapy fail, a combination with conversion from tacrolimus to cyclosporine can effectively improve the anemia without graft dysfunction.

Citation： GAO Peijuan, SHI Yunying, PU Wenshen, TAO Ye. Clinical characteristics and treatment of six kidney recipients with human parvovirus B19 infection. West China Medical Journal, 2019, 34(7): 769-776. doi: 10.7507/1002-0179.201905234 Copy

1.	Neild G, Anderson M, Hawes S, et al. Parvovirus infection after renal transplant. Lancet, 1986, 2(8517): 1226-1227.
2.	Kaufmann B, Simpson AA, Rossmann MG. The structure of human parvovirus B19. Proc Natl Acad Sci USA, 2004, 101(32): 11628-11633.
3.	Waldman M, Kopp JB. Parvovirus B19 and the Kidney. Clin J Am Soc Nephrol, 2007, 2(Suppl 1): S47-S56.
4.	Molnar MZ, Czira M, Ambrus C, et al. Anemia is associated with mortality in kidney-transplanted patients? A prospective cohort study. Am J Transplant, 2007, 7(4): 818-824.
5.	Gallinella G. The clinical use of parvovirus B19 assays: recent advances. Expert Rev Mol Diagn, 2018, 18(9): 821-832.
6.	Bodewes R, Kerkhof J, Cremer J, et al. Oral fluid: non-invasive alternative for parvovirus B19 diagnosis?. J Clin Virol, 2019, 117: 5-10.
7.	林果为, 王吉耀, 葛均波. 实用内科学: 下册. 15 版. 北京: 人民卫生出版社, 2017: 1682-1686.
8.	Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant, 2009, 9(Suppl 3): S1-S155.
9.	张健, 陶冶. 肾移植术后贫血的危险因素. 肾脏病与透析肾移植杂志, 2018, 27(4): 387-390.
10.	Quarello P, Garelli E, Brusco A, et al. Multiplex ligation-dependent probe amplification enhances molecular diagnosis of Diamond-Blackfan anemia due to RPS19 deficiency. Haematologica, 2008, 93(11): 1748-1750.
11.	Vlachos A, Ball S, Dahl N, et al. Diagnosing and treating Diamond Blackfan anaemia: results of an international clinical consensus conference. Br J Haematol, 2008, 142(6): 859-876.
12.	Deeren D. A kidney transplant patient with pure red cell aplasia: first things first!. Ann Hematol, 2011, 90(8): 991-992.
13.	Waki F, Ohnishi H, Shintani T, et al. Linezolid-induced pure red cell aplasia in a patient with Staphylococcus epidermidis infection after allogeneic stem cell transplantation. Transpl Infect Dis, 2012, 14(4): E1-E6.
14.	Engelen W, Verpooten GA, Van der Planken M, et al. 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.
15.	Koduri PR, Vanajakshi S, Anuradha R. Azathioprine-associated pure red cell aplasia in renal transplant recipients: a report of two cases. Ann Hematol, 2014, 93(2): 329-330.
16.	Bernard C, Frih H, Pasquet F, et al. Thymoma associated with autoimmune diseases: 85 cases and literature review. Autoimmun Rev, 2016, 15(1): 82-92.
17.	Kelly HA, Siebert D, Hammond R, et al. The age-specific prevalence of human parvovirus immunity in Victoria, Australia compared with other parts of the world. Epidemiol Infect, 2000, 124(3): 449-457.
18.	Baek CH, Kim H, Yang WS, et al. Risk factors and long-term outcomes of parvovirus B19 infection in kidney transplant patients. Transpl Infect Dis, 2017, 19(5): e12754.
19.	Avila-Casado MC, Vargas-Alarcon G, Soto ME, et al. Familial collapsing glomerulopathy: clinical, pathological and immunogenetic features. Kidney Int, 2003, 63(1): 233-239.
20.	Besse W, Mansour S, Jatwani K, et al. Collapsing glomerulopathy in a young woman with APOL1 risk alleles following acute parvovirus B19 infection: a case report investigation. BMC Nephrol, 2016, 17(1): 125.
21.	Eid AJ, Brown RA, Patel R, et al. Parvovirus B19 infection after transplantation: a review of 98 cases. Clin Infect Dis, 2006, 43(1): 40-48.
22.	Young NS, Brown KE. Parvovirus B19. N Engl J Med, 2004, 350(6): 586-597.
23.	Peterlana D, Puccetti A, Corrocher R, et al. Serologic and molecular detection of human parvovirus B19 infection. Clin Chim Acta, 2006, 372(1/2): 14-23.
24.	Crabol Y, Terrier B, Rozenberg F, et al. Intravenous immunoglobulin therapy for pure red cell aplasia related to human parvovirus B19 infection: a retrospective study of 10 patients and review of the literature. Clin Infect Dis, 2013, 56(7): 968-977.
25.	Zachary AA, Leffell MS. Desensitization for solid organ and hematopoietic stem cell transplantation. Immunol Rev, 2014, 258(1): 183-207.
26.	Koduri PR, Kumapley R, Valladares J, et al. Chronic pure red cell aplasia caused by parvovirus B19 in AIDS: use of intravenous immunoglobulin—a report of eight patients. Am J Hematol, 1999, 61(1): 16-20.
27.	Koduri PR, Kumapley R, Khokha ND, et al. Red cell aplasia caused by parvovirus B19 in AIDS: use of i.v. immunoglobulin. Ann Hematol, 1997, 75(1-2): 67-68.
28.	李帅阳, 沈兵, 刘志宏, 等. 肾移植术后人微小病毒 B19 感染导致纯红细胞增生障碍性贫血. 现代生物医学进展, 2012, 12(14): 2698-2702.
29.	Röhrer C, Gärtner B, Sauerbrei A, et al. Seroprevalence of parvovirus B19 in the German population. Epidemiol Infect, 2008, 136(11): 1564-1575.
30.	Levy JB, Pusey CD. Nephrotoxicity of intravenous immunoglobulin. QJM, 2000, 93(11): 751-755.
31.	Luke PP, Scantlebury VP, Jordan ML, et al. Reversal of steroid-and anti-lymphocyte antibody-resistant rejection using intravenous immunoglobulin (IVIG) in renal transplant recipients. Transplantation, 2001, 72(3): 419-422.
32.	Qiu J, Söderlund-Venermo M, Young NS. Human parvoviruses. Clin Microbiol Rev, 2017, 30(1): 43-113.
33.	Rodríguez Faba O, Boissier R, Budde K, et al. European association of urology guidelines on renal transplantation: update 2018. Eur Urol Focus, 2018, 4(2): 208-215.
34.	Beckhoff A, Steffen I, Sandoz P, et al. Relapsing severe anaemia due to primary parvovirus B19 infection after renal transplantation: a case report and review of the literature. Nephrol Dial Transplant, 2007, 22(12): 3660-3663.
35.	Abongwa C, Abusin G, El-Sheikh A. Successful treatment of tacrolimus-related pure red cell aplasia and autoimmune hemolytic anemia with rituximab in a pediatric cardiac transplant patient. Pediatr Blood Cancer, 2017, 64(12): e26674.
36.	Gregoor PS, Weimar W. Tacrolimus and pure red-cell aplasia. Am J Transplant, 2005, 5(1): 195-196.
37.	Winkler M, Schulze F, Jost U, et al. Anaemia associated with FK 506 immunosuppression. Lancet, 1993, 341(8851): 1035-1036.
38.	Dao AT, Yamazaki H, Takamatsu H, et al. Cyclosporine restores hematopoietic function by compensating for decreased tregs in patients with pure red cell aplasia and acquired aplastic anemia. Ann Hematol, 2016, 95(5): 771-781.
39.	Almonte M, Velásquez-Jones L, Valverde S, et al. Post-renal transplant erythrocytosis: a case report. Pediatr Transplant, 2015, 19(1): E7-E10.
40.	Lien YH. Top 10 things primary care physicians should know about maintenance immunosuppression for transplant recipients. Am J Med, 2016, 129(6): 568-572.
41.	Shimmura H, Tanabe K, Ishikawa N, et al. Discontinuation of immunosuppressive antimetabolite for parvovirus B19-associated anemia in kidney transplant patients. Transplant Proc, 2000, 32(7): 1967-1970.
42.	Geetha D, Zachary JB, Baldado HM, et al. 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(6): 586-591.
43.	Ramage JK, Hale A, Gane E, et al. Parvovirus B19-induced red cell aplasia treated with plasmapheresis and immunoglobulin. Lancet, 1994, 343(8898): 667-668.
44.	Rivas-Delgado A, Matutes E, Rozman M. Recurrent pure red cell aplasia in a hepatorenal transplant recipient with chronic parvovirus B19 infection. Br J Haematol, 2016, 172(4): 495.

1. Neild G, Anderson M, Hawes S, et al. Parvovirus infection after renal transplant. Lancet, 1986, 2(8517): 1226-1227.
2. Kaufmann B, Simpson AA, Rossmann MG. The structure of human parvovirus B19. Proc Natl Acad Sci USA, 2004, 101(32): 11628-11633.
3. Waldman M, Kopp JB. Parvovirus B19 and the Kidney. Clin J Am Soc Nephrol, 2007, 2(Suppl 1): S47-S56.
4. Molnar MZ, Czira M, Ambrus C, et al. Anemia is associated with mortality in kidney-transplanted patients? A prospective cohort study. Am J Transplant, 2007, 7(4): 818-824.
5. Gallinella G. The clinical use of parvovirus B19 assays: recent advances. Expert Rev Mol Diagn, 2018, 18(9): 821-832.
6. Bodewes R, Kerkhof J, Cremer J, et al. Oral fluid: non-invasive alternative for parvovirus B19 diagnosis?. J Clin Virol, 2019, 117: 5-10.
7. 林果为, 王吉耀, 葛均波. 实用内科学: 下册. 15 版. 北京: 人民卫生出版社, 2017: 1682-1686.
8. Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant, 2009, 9(Suppl 3): S1-S155.
9. 张健, 陶冶. 肾移植术后贫血的危险因素. 肾脏病与透析肾移植杂志, 2018, 27(4): 387-390.
10. Quarello P, Garelli E, Brusco A, et al. Multiplex ligation-dependent probe amplification enhances molecular diagnosis of Diamond-Blackfan anemia due to RPS19 deficiency. Haematologica, 2008, 93(11): 1748-1750.
11. Vlachos A, Ball S, Dahl N, et al. Diagnosing and treating Diamond Blackfan anaemia: results of an international clinical consensus conference. Br J Haematol, 2008, 142(6): 859-876.
12. Deeren D. A kidney transplant patient with pure red cell aplasia: first things first!. Ann Hematol, 2011, 90(8): 991-992.
13. Waki F, Ohnishi H, Shintani T, et al. Linezolid-induced pure red cell aplasia in a patient with Staphylococcus epidermidis infection after allogeneic stem cell transplantation. Transpl Infect Dis, 2012, 14(4): E1-E6.
14. Engelen W, Verpooten GA, Van der Planken M, et al. 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.
15. Koduri PR, Vanajakshi S, Anuradha R. Azathioprine-associated pure red cell aplasia in renal transplant recipients: a report of two cases. Ann Hematol, 2014, 93(2): 329-330.
16. Bernard C, Frih H, Pasquet F, et al. Thymoma associated with autoimmune diseases: 85 cases and literature review. Autoimmun Rev, 2016, 15(1): 82-92.
17. Kelly HA, Siebert D, Hammond R, et al. The age-specific prevalence of human parvovirus immunity in Victoria, Australia compared with other parts of the world. Epidemiol Infect, 2000, 124(3): 449-457.
18. Baek CH, Kim H, Yang WS, et al. Risk factors and long-term outcomes of parvovirus B19 infection in kidney transplant patients. Transpl Infect Dis, 2017, 19(5): e12754.
19. Avila-Casado MC, Vargas-Alarcon G, Soto ME, et al. Familial collapsing glomerulopathy: clinical, pathological and immunogenetic features. Kidney Int, 2003, 63(1): 233-239.
20. Besse W, Mansour S, Jatwani K, et al. Collapsing glomerulopathy in a young woman with APOL1 risk alleles following acute parvovirus B19 infection: a case report investigation. BMC Nephrol, 2016, 17(1): 125.
21. Eid AJ, Brown RA, Patel R, et al. Parvovirus B19 infection after transplantation: a review of 98 cases. Clin Infect Dis, 2006, 43(1): 40-48.
22. Young NS, Brown KE. Parvovirus B19. N Engl J Med, 2004, 350(6): 586-597.
23. Peterlana D, Puccetti A, Corrocher R, et al. Serologic and molecular detection of human parvovirus B19 infection. Clin Chim Acta, 2006, 372(1/2): 14-23.
24. Crabol Y, Terrier B, Rozenberg F, et al. Intravenous immunoglobulin therapy for pure red cell aplasia related to human parvovirus B19 infection: a retrospective study of 10 patients and review of the literature. Clin Infect Dis, 2013, 56(7): 968-977.
25. Zachary AA, Leffell MS. Desensitization for solid organ and hematopoietic stem cell transplantation. Immunol Rev, 2014, 258(1): 183-207.
26. Koduri PR, Kumapley R, Valladares J, et al. Chronic pure red cell aplasia caused by parvovirus B19 in AIDS: use of intravenous immunoglobulin—a report of eight patients. Am J Hematol, 1999, 61(1): 16-20.
27. Koduri PR, Kumapley R, Khokha ND, et al. Red cell aplasia caused by parvovirus B19 in AIDS: use of i.v. immunoglobulin. Ann Hematol, 1997, 75(1-2): 67-68.
28. 李帅阳, 沈兵, 刘志宏, 等. 肾移植术后人微小病毒 B19 感染导致纯红细胞增生障碍性贫血. 现代生物医学进展, 2012, 12(14): 2698-2702.
29. Röhrer C, Gärtner B, Sauerbrei A, et al. Seroprevalence of parvovirus B19 in the German population. Epidemiol Infect, 2008, 136(11): 1564-1575.
30. Levy JB, Pusey CD. Nephrotoxicity of intravenous immunoglobulin. QJM, 2000, 93(11): 751-755.
31. Luke PP, Scantlebury VP, Jordan ML, et al. Reversal of steroid-and anti-lymphocyte antibody-resistant rejection using intravenous immunoglobulin (IVIG) in renal transplant recipients. Transplantation, 2001, 72(3): 419-422.
32. Qiu J, Söderlund-Venermo M, Young NS. Human parvoviruses. Clin Microbiol Rev, 2017, 30(1): 43-113.
33. Rodríguez Faba O, Boissier R, Budde K, et al. European association of urology guidelines on renal transplantation: update 2018. Eur Urol Focus, 2018, 4(2): 208-215.
34. Beckhoff A, Steffen I, Sandoz P, et al. Relapsing severe anaemia due to primary parvovirus B19 infection after renal transplantation: a case report and review of the literature. Nephrol Dial Transplant, 2007, 22(12): 3660-3663.
35. Abongwa C, Abusin G, El-Sheikh A. Successful treatment of tacrolimus-related pure red cell aplasia and autoimmune hemolytic anemia with rituximab in a pediatric cardiac transplant patient. Pediatr Blood Cancer, 2017, 64(12): e26674.
36. Gregoor PS, Weimar W. Tacrolimus and pure red-cell aplasia. Am J Transplant, 2005, 5(1): 195-196.
37. Winkler M, Schulze F, Jost U, et al. Anaemia associated with FK 506 immunosuppression. Lancet, 1993, 341(8851): 1035-1036.
38. Dao AT, Yamazaki H, Takamatsu H, et al. Cyclosporine restores hematopoietic function by compensating for decreased tregs in patients with pure red cell aplasia and acquired aplastic anemia. Ann Hematol, 2016, 95(5): 771-781.
39. Almonte M, Velásquez-Jones L, Valverde S, et al. Post-renal transplant erythrocytosis: a case report. Pediatr Transplant, 2015, 19(1): E7-E10.
40. Lien YH. Top 10 things primary care physicians should know about maintenance immunosuppression for transplant recipients. Am J Med, 2016, 129(6): 568-572.
41. Shimmura H, Tanabe K, Ishikawa N, et al. Discontinuation of immunosuppressive antimetabolite for parvovirus B19-associated anemia in kidney transplant patients. Transplant Proc, 2000, 32(7): 1967-1970.
42. Geetha D, Zachary JB, Baldado HM, et al. 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(6): 586-591.
43. Ramage JK, Hale A, Gane E, et al. Parvovirus B19-induced red cell aplasia treated with plasmapheresis and immunoglobulin. Lancet, 1994, 343(8898): 667-668.
44. Rivas-Delgado A, Matutes E, Rozman M. Recurrent pure red cell aplasia in a hepatorenal transplant recipient with chronic parvovirus B19 infection. Br J Haematol, 2016, 172(4): 495.

West China Medical Journal

Clinical characteristics and treatment of six kidney recipients with human parvovirus B19 infection

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