Advertisement

Current Transplantation Reports

, Volume 6, Issue 2, pp 167–176 | Cite as

Living Kidney Donation in Individuals with Hepatitis C and HIV Infection: Rationale and Emerging Evidence

  • Luckmini Liyanage
  • Abimereki D. Muzaale
  • Macey L. Henderson
  • Christine M. DurandEmail author
Live Kidney Donation (K Lentine and R Schaffer, Section Editors)
  • 18 Downloads
Part of the following topical collections:
  1. Topical Collection on Live Kidney Donation

Abstract

Purpose of Review

HIV-infected (HIV+) and hepatitis C virus-infected (HCV+) individuals with end-stage renal disease (ESRD) have decreased access to kidney transplantation. With new opportunities provided by the HIV Organ Policy Equity (HOPE) Act and direct-acting antivirals (DAAs) for HCV, we explore the potential risks and benefits of living-donor kidney transplantation from HIV+ or HCV+ donors from the perspective of both donor health and recipient outcomes.

Recent Findings

The HOPE Act permits organ donation from both deceased and living HIV+ persons to HIV+ recipients; however, there is only a clinical experience with HIV+ deceased donors to date. Empirical evidence demonstrates a low but acceptable risk of ESRD in potential HIV+ living donors without comorbidities who have well-controlled infection in the absence of donation. With the availability of potent DAAs for eradication of HCV infection, growing evidence shows good outcomes with HCV-seropositive and/or -viremic deceased kidney donors providing rationale to consider HCV+ living donors.

Summary

HIV+ and HCV+ living-donor kidney transplantations may improve access to transplant for vulnerable ESRD populations. Careful evaluation and monitoring are warranted to mitigate potential risks to donors and recipients.

Keywords

HIV Hepatitis C Living donor Living-donor transplantation HIV Organ Policy Equity Act Direct-acting antivirals 

Notes

Acknowledgements

This work was supported in part from the National Cancer Institute (Durand, K23CA177321-01A1) and National Institute of Diabetes and Digestive and Kidney Diseases (Segev, K24DK101828 and R01AI120938) and the JHU Center for AIDS Research 1P30AI094189.

Compliance with Ethical Standards

Conflict of Interest

Macey Henderson is a member of the OPTN/UNOS board of directors.

Luckmini Liyanage, Abimereki D. Muzaale, and Christine M. Durand declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Jotwani V, Li Y, Grunfeld C, Choi AI, Shlipak MG. Risk factors for ESRD in HIV-infected individuals: traditional and HIV-related factors. Am J Kidney Dis. 2012;59(5):628–35.Google Scholar
  2. 2.
    •• Muzaale AD, Althoff KN, Sperati CJ, Abraham AG, Kucirka LM, Massie AB, et al. Risk of end-stage renal disease in HIV-positive potential live kidney donors. Am J Transplant. 2017;17(7):1823–32 In this large database study, the addition risk of developing ESRD after living kidney donation due to HIV was found to vary substantially based on the base case, but in the low risk scenario may be considered a relative contraindication rather than absolute contraindication to donation.Google Scholar
  3. 3.
    Cohen-Bucay A, Francis JM, Gordon CE. Timing of hepatitis C virus infection treatment in kidney transplant candidates. Hemodial Int. 2018;22(Suppl 1):S61–70.Google Scholar
  4. 4.
    Trullas JC, et al. Outcome and prognostic factors in HIV-1-infected patients on dialysis in cART era: a GESIDA/SEN cohort study. J Acquir Immune Defic Syndr. 2011;57(4):276–83.Google Scholar
  5. 5.
    Stock PG, Barin B, Murphy B, Hanto D, Diego JM, Light J, et al. Outcomes of kidney transplantation in HIV-infected recipients. N Engl J Med. 2010;363(21):2004–14.Google Scholar
  6. 6.
    Locke JE, Mehta S, Reed RD, MacLennan P, Massie A, Nellore A, et al. A national study of outcomes among HIV-infected kidney transplant recipients. J Am Soc Nephrol. 2015;26(9):2222–9.Google Scholar
  7. 7.
    Locke JE, Reed RD, Mehta SG, Durand C, Mannon RB, MacLennan P, et al. Center-level experience and kidney transplant outcomes in HIV-infected recipients. Am J Transplant. 2015;15(8):2096–104.Google Scholar
  8. 8.
    Locke JE, Gustafson S, Mehta S, Reed RD, Shelton B, MacLennan PA, et al. Survival benefit of kidney transplantation in HIV-infected patients. Ann Surg. 2017;265(3):604–8.Google Scholar
  9. 9.
    Gathogo E, Jose S, Jones R, Levy JB, Mackie NE, Booth J, et al. End-stage kidney disease and kidney transplantation in HIV-positive patients: an observational cohort study. J Acquir Immune Defic Syndr. 2014;67(2):177–80.Google Scholar
  10. 10.
    Gathogo EN, Hamzah L, Hilton R, Marshall N, Ashley C, Harber M, et al. Kidney transplantation in HIV-positive adults: the UK experience. Int J STD AIDS. 2014;25(1):57–66.Google Scholar
  11. 11.
    Shaffer AA, Durand CM. Solid organ transplantation for HIV-infected individuals. Curr Treat Options Infect Dis. 2018;10(1):107–20.Google Scholar
  12. 12.
    National Kidney Foundation. Hepatitis C management and hemodialysis 2017 [cited 2019 January 1]; Available from: https://www.kidney.org/professionals/KDOQI/12-10-1601.
  13. 13.
    Goodkin DA, Bieber B, Jadoul M, Martin P, Kanda E, Pisoni RL. Mortality, hospitalization, and quality of life among patients with hepatitis C infection on hemodialysis. Clin J Am Soc Nephrol. 2017;12(2):287–97.Google Scholar
  14. 14.
    Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C Work Group. KDIGO. Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int Suppl. 2018;2018(8):91–165.Google Scholar
  15. 15.
    Fabrizi F, Martin P, Dixit V, Messa P. Meta-analysis of observational studies: hepatitis C and survival after renal transplant. J Viral Hepat. 2014;21(5):314–24.Google Scholar
  16. 16.
    Baid-Agrawal S, Schindler R, Reinke P, Staedtler A, Rimpler S, Malik B, et al. Prevalence of occult hepatitis C infection in chronic hemodialysis and kidney transplant patients. J Hepatol. 2014;60(5):928–33.Google Scholar
  17. 17.
    Scott DR, Wong JKW, Spicer TS, Dent H, Mensah FK, McDonald S, et al. Adverse impact of hepatitis C virus infection on renal replacement therapy and renal transplant patients in Australia and New Zealand. Transplantation. 2010;90(11):1165–71.Google Scholar
  18. 18.
    Cruzado JM, Carrera M, Torras J, Grinyo JM. Hepatitis C virus infection and de novo glomerular lesions in renal allografts. Am J Transplant. 2001;1(2):171–8.Google Scholar
  19. 19.
    Fabrizi F, Messa P, Martin P, Takkouche B. Hepatitis C virus infection and post-transplant diabetes mellitus among renal transplant patients: a meta-analysis. Int J Artif Organs. 2008;31(8):675–82.Google Scholar
  20. 20.
    Diaz JM, et al. Risk factors for cardiovascular disease after renal transplantation. Transplant Proc. 2003;35(5):1722–4.Google Scholar
  21. 21.
    Bloom RD, Sayer G, Fa K, Constantinescu S, Abt P, Reddy KR. Outcomes of hepatitis C-virus infected kidney transplant candidates who remain on the waiting list. Am J Transplant. 2005;5(1):139–44.Google Scholar
  22. 22.
    Ingsathit A, Kamanamool N, Thakkinstian A, Sumethkul V. Survival advantage of kidney transplantation over dialysis in patients with hepatitis C: a systematic review and meta-analysis. Transplantation. 2013;95(7):943–8.Google Scholar
  23. 23.
    Locke JE, Mehta S, Sawinski D, Gustafson S, Shelton BA, Reed RD, et al. Access to kidney transplantation among HIV-infected waitlist candidates. Clin J Am Soc Nephrol. 2017;12(3):467–75.Google Scholar
  24. 24.
    Cohen JB, Locke JE, Shelton B, Reed RD, Mustian M, MacLennan P, et al. Disparity in access to kidney allograft offers among transplant candidates with human immunodeficiency virus. Clin Transpl. 2018;21:e31466.  https://doi.org/10.1111/ctr.13466.Google Scholar
  25. 25.
    Department of Health and Human Services. Organ procurement and transplantation: implementation of the HIV Organ Policy Equity Act. Final rule. Fed Regist. 2015;80(89):26464–7.Google Scholar
  26. 26.
    • Muller E, Barday Z, Mendelson M, Kahn D. HIV-positive-to-HIV-positive kidney transplantation--results at 3 to 5 years. N Engl J Med. 2015;372(7):613–20 This landmark study presents encouraging results on the first cohort of HIV+ to HIV+ kidney transplant recipients in South Africa.Google Scholar
  27. 27.
    Muller E, Kahn D, Mendelson M. Renal transplantation between HIV-positive donors and recipients. N Engl J Med. 2010;362(24):2336–7.Google Scholar
  28. 28.
    Wigneswaran J, van Wyck D, Pegues D, Gholam P, Nissenson AR. Hepatitis C virus infection in patients with end-stage renal disease. Hemodial Int. 2018;22(3):297–307.Google Scholar
  29. 29.
    Colombo M, Aghemo A, Liu H, Zhang J, Dvory-Sobol H, Hyland R, et al. Treatment with ledipasvir-sofosbuvir for 12 or 24 weeks in kidney transplant recipients with chronic hepatitis C virus genotype 1 or 4 infection: a randomized trial. Ann Intern Med. 2017;166(2):109–17.Google Scholar
  30. 30.
    Gane E, Lawitz E, Pugatch D, Papatheodoridis G, Bräu N, Brown A, et al. Glecaprevir and pibrentasvir in patients with HCV and severe renal impairment. N Engl J Med. 2017;377(15):1448–55.Google Scholar
  31. 31.
    HCV Guidance: Recommendations for testing, managing, and treating hepatitis C [internet]. Recommendations for testing, managing, and treating hepatitis C | HCV Guidance. [cited 2019Jan11]. Available from: https://www.hcvguidelines.org/.
  32. 32.
    Levitsky J, Formica RN, Bloom RD, Charlton M, Curry M, Friedewald J, et al. The American Society of Transplantation Consensus Conference on the use of hepatitis C viremic donors in solid organ transplantation. Am J Transplant. 2017;17(11):2790–802.Google Scholar
  33. 33.
    Kucirka LM, Sarathy H, Govindan P, Wolf JH, Ellison TA, Hart LJ, et al. Risk of window period hepatitis-C infection in high infectious risk donors: systematic review and meta-analysis. Am J Transplant. 2011;11(6):1188–200.Google Scholar
  34. 34.
    Kucirka LM, Singer AL, Ros RL, Montgomery RA, Dagher NN, Segev DL. Underutilization of hepatitis C-positive kidneys for hepatitis C-positive recipients. Am J Transplant. 2010;10(5):1238–46.  https://doi.org/10.1111/j.1600-6143.2010.03091.x.Google Scholar
  35. 35.
    Kucirka LM, Peters TG, Segev DL. Impact of donor hepatitis C virus infection on death and need for liver transplant in hepatitis C virus-positive kidney transplant recipients. Am J Kidney Dis. 2012;60(1):112–20.  https://doi.org/10.1053/j.ajkd.2012.03.015.Google Scholar
  36. 36.
    Elmasry S, Wadhwa S, Bang BR, Cook L, Chopra S, Kanel G, et al. Detection of occult hepatitis C virus infection in patients who achieved a sustained virologic response to direct-acting antiviral agents for recurrent infection after liver transplantation. Gastroenterology. 2017;152(3):550–553 e8.Google Scholar
  37. 37.
    Tokumoto T, Tanabe K, Simizu T, Shimmura H, Iizuka J, Ishikawa N, et al. Kidney transplantation from a donor who is HCV antibody positive and HCV-RNA negative. Transplant Proc. 2000;32(7):1597–9.Google Scholar
  38. 38.
    Cruzado JM, Gil-Vernet S, Castellote J, Bestard O, Melilli E, Grinyó JM. Successful treatment of chronic HCV infection should not preclude kidney donation to an HCV negative recipient. Am J Transplant. 2013;13(10):2773–4.Google Scholar
  39. 39.
    • Goldberg DS, Abt PL, Blumberg EA, van Deerlin VM, Levine M, Reddy KR, et al. Trial of transplantation of HCV-infected kidneys into uninfected recipients. N Engl J Med. 2017;376(24):2394–5 This letter to the editor presents the initial results of a pilot clinical trial curing HCV in HCV-negative recipients transplanted with HCV NAT-positive donor kidneys.Google Scholar
  40. 40.
    • Durand CM, Bowring MG, Brown DM, Chattergoon MA, Massaccesi G, Bair N, et al. Direct-acting antiviral prophylaxis in kidney transplantation from hepatitis C virus-infected donors to noninfected recipients: an open-label nonrandomized trial. Ann Intern Med. 2018;168(8):533–40. This paper presents initial results of a clinical trial investigating DAA prophylaxis to prevent HCV in HCV-negative recipients transplanted with HCV NAT-positive donor kidneys.Google Scholar
  41. 41.
    Redd AD, Quinn TC, Tobian AA. Frequency and implications of HIV superinfection. Lancet Infect Dis. 2013;13(7):622–8.Google Scholar
  42. 42.
    Muzaale AD, Massie AB, Kucirka LM, Luo X, Kumar K, Brown RS, et al. Outcomes of live kidney donors who develop end-stage renal disease. Transplantation. 2016;100(6):1306–12.  https://doi.org/10.1097/TP.0000000000000920.Google Scholar
  43. 43.
    •• Final Human Immunodeficiency Virus Organ Policy Equity (HOPE) Act safeguards and research criteria for transplantation of organs infected with HIV. Fed Regist, 2015. 80: p. 34912–21. A delineation of the important safeguards and research criteria required under the HOPE Act to protect HIV+ living donors and HIV+ recipients of HIV+ deceased and HIV+ living donor organs. Google Scholar
  44. 44.
    Rodriguez RA, et al. Determinants of survival among HIV-infected chronic dialysis patients. J Am Soc Nephrol. 2003;14(5):1307–13.Google Scholar
  45. 45.
    Durand CM, Segev D, Sugarman J. Realizing HOPE: the ethics of organ transplantation from HIV-positive donors. Ann Intern Med. 2016;165(2):138–42.Google Scholar
  46. 46.
    Boyarsky BJ, Hall EC, Singer AL, Montgomery RA, Gebo KA, Segev DL. Estimating the potential pool of HIV-infected deceased organ donors in the United States. Am J Transplant. 2011;11(6):1209–17.Google Scholar
  47. 47.
    Wyatt CM. Kidney disease and HIV infection. Top Antivir Med. 2017;25(1):13–6.Google Scholar
  48. 48.
    Abraham AG, Althoff KN, Jing Y, Estrella MM, Kitahata MM, Wester CW, et al. End-stage renal disease among HIV-infected adults in North America. Clin Infect Dis. 2015;60(6):941–9.Google Scholar
  49. 49.
    Lucas GM, Ross MJ, Stock PG, Shlipak MG, Wyatt CM, Gupta SK, et al. Clinical practice guideline for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(9):e96–138.Google Scholar
  50. 50.
    Gopalakrishnan I, Iskandar SS, Daeihagh P, Divers J, Langefeld CD, Bowden DW, et al. Coincident idiopathic focal segmental glomerulosclerosis collapsing variant and diabetic nephropathy in an African American homozygous for MYH9 risk variants. Hum Pathol. 2011;42(2):291–4.Google Scholar
  51. 51.
    Kaufman L, Collins SE, Klotman PE. The pathogenesis of HIV-associated nephropathy. Adv Chronic Kidney Dis. 2010;17(1):36–43.Google Scholar
  52. 52.
    Grams ME, Garg AX, Lentine KL. Kidney-failure risk projection for the living kidney-donor candidate. N Engl J Med. 2016;374(21):2094–5.Google Scholar
  53. 53.
    Izzedine H, Harris M, Perazella MA. The nephrotoxic effects of HAART. Nat Rev Nephrol. 2009;5(10):563–73.Google Scholar
  54. 54.
    Jafari A, Khalili H, Dashti-Khavidaki S. Tenofovir-induced nephrotoxicity: incidence, mechanism, risk factors, prognosis and proposed agents for prevention. Eur J Clin Pharmacol. 2014;70(9):1029–40.Google Scholar
  55. 55.
    Mocroft A, Lundgren JD, Ross M, Fux CA, Reiss P, Moranne O, et al. Cumulative and current exposure to potentially nephrotoxic antiretrovirals and development of chronic kidney disease in HIV-positive individuals with a normal baseline estimated glomerular filtration rate: a prospective international cohort study. Lancet HIV. 2016;3(1):e23–32.Google Scholar
  56. 56.
    Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI, et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science. 2010;329(5993):841–5.Google Scholar
  57. 57.
    Kopp JB, Nelson GW, Sampath K, Johnson RC, Genovese G, An P, et al. APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy. J Am Soc Nephrol. 2011;22(11):2129–37.Google Scholar
  58. 58.
    Nguyen AQ, Anjum SK, Halpern SE, Kumar K, van Pilsum Rasmussen SE, Doby B, et al. Willingness to donate organs among people living with HIV. J Acquir Immune Defic Syndr. 2018;79(1):e30–6.Google Scholar
  59. 59.
    • Van Pilsum Rasmussen SE, et al. Perceptions, motivations, and concerns about living organ donation among people living with HIV. AIDS Care. 2018:1–5 This qualitative study of potential HIV+ living donors described potential concerns and benefits of living kidney donation in this population.Google Scholar
  60. 60.
    Malani P. HIV and transplantation: new reasons for HOPE. JAMA. 2016;316(2):136–8.Google Scholar
  61. 61.
    •• Jadoul M, Berenguer MC, Doss W, Fabrizi F, Izopet J, Jha V, et al. Executive summary of the 2018 KDIGO Hepatitis C in CKD Guideline: welcoming advances in evaluation and management. Kidney Int. 2018;94(4):663–73 Summary of KDIGO guidelines regarding HCV+ donor and recipient kidney transplantation.Google Scholar
  62. 62.
    Chascsa DM, Mousa OY, Pungpapong S, Zhang N, Chervenak A, Nidamanuri S, et al. Clinical outcomes of hepatitis C treatment before and after kidney transplantation and its impact on time to transplant: a multicenter study. Am J Transplant. 2018;18(10):2559–65.Google Scholar
  63. 63.
    Lee, et al. Con: use of hepatitis C virus-positive donors should be restricted to research protocols. Clinical Liver Disease. 2018;12:105–8.  https://doi.org/10.1002/cld.744.Google Scholar
  64. 64.
    Werbel WA, Durand CM. Pro: use of hepatitis C virus-positive donors should be considered standard of care. Clinical Liver Disease. 2018;12:100–4.  https://doi.org/10.1002/cld.743.Google Scholar
  65. 65.
    Schlendorf KH, Zalawadiya S, Shah AS, Wigger M, Chung CY, Smith S, et al. Early outcomes using hepatitis C-positive donors for cardiac transplantation in the era of effective direct-acting anti-viral therapies. J Heart Lung Transplant. 2018;37(6):763–9.Google Scholar
  66. 66.
    Kwong AJ, Wall A, Melcher M, Wang U, Ahmed A, Subramanian A, et al. Liver transplantation for hepatitis C virus (HCV) non-viremic recipients with HCV viremic donors. Am J Transplant. 2018.  https://doi.org/10.1111/ajt.15162.
  67. 67.
    (USRDS), U.R.D.S., Annual Data Report. 2018.2.Google Scholar
  68. 68.
    Gozdowska J, Zatorski M, Torchalla P, Białek Ł, Bojanowska A, Tomaszek A, et al. Living-donor versus deceased-donor kidney transplantation: comparison of psychosocial consequences for recipients. Transplant Proc. 2016;48(5):1498–505.Google Scholar
  69. 69.
    Ladino M, Pedraza F, Roth D. Hepatitis C virus infection in chronic kidney disease. J Am Soc Nephrol. 2016;27(8):2238–46.  https://doi.org/10.1681/ASN.2016010030.Google Scholar
  70. 70.
    Chapman JR. KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors 2017 [internet]. KDIGO. KDIGO; [cited 2018Nov14]. Available from: https://kdigo.org/wp-content/uploads/2017/07/2017-KDIGO-LD-GL.pdf
  71. 71.
    Morales JM, Kamar N, Rostaing L. Hepatitis C and renal disease: epidemiology, diagnosis, pathogenesis and therapy. Contrib Nephrol. 2012;176:10–23.Google Scholar
  72. 72.
    Sumida K, Ubara Y, Hoshino J, Suwabe T, Nakanishi S, Hiramatsu R, et al. Hepatitis C virus-related kidney disease: various histological patterns. Clin Nephrol. 2010;74(6):446–56.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Luckmini Liyanage
    • 1
  • Abimereki D. Muzaale
    • 2
  • Macey L. Henderson
    • 2
  • Christine M. Durand
    • 1
    • 3
    Email author
  1. 1.Department of Medicine and OncologyJohns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Department of SurgeryJohns Hopkins University School of MedicineBaltimoreUSA
  3. 3.Sidney Kimmel Cancer CenterJohns Hopkins University School of MedicineBaltimoreUSA

Personalised recommendations