Living Kidney Donation in Individuals with Hepatitis C and HIV Infection: Rationale and Emerging Evidence
- 18 Downloads
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.
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.
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.
KeywordsHIV Hepatitis C Living donor Living-donor transplantation HIV Organ Policy Equity Act Direct-acting antivirals
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.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 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.•• 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.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.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.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.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.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.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.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.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.Shaffer AA, Durand CM. Solid organ transplantation for HIV-infected individuals. Curr Treat Options Infect Dis. 2018;10(1):107–20.Google Scholar
- 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.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.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.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.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.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.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.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.Diaz JM, et al. Risk factors for cardiovascular disease after renal transplantation. Transplant Proc. 2003;35(5):1722–4.Google Scholar
- 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.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.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
- 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.• 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.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.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.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.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.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.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.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
- 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.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.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.• 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.• 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.Redd AD, Quinn TC, Tobian AA. Frequency and implications of HIV superinfection. Lancet Infect Dis. 2013;13(7):622–8.Google Scholar
- 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.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.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.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.Wyatt CM. Kidney disease and HIV infection. Top Antivir Med. 2017;25(1):13–6.Google Scholar
- 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.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.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.Kaufman L, Collins SE, Klotman PE. The pathogenesis of HIV-associated nephropathy. Adv Chronic Kidney Dis. 2010;17(1):36–43.Google Scholar
- 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.Izzedine H, Harris M, Perazella MA. The nephrotoxic effects of HAART. Nat Rev Nephrol. 2009;5(10):563–73.Google Scholar
- 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.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.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.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.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.• 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.Malani P. HIV and transplantation: new reasons for HOPE. JAMA. 2016;316(2):136–8.Google Scholar
- 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.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
- 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.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.(USRDS), U.R.D.S., Annual Data Report. 2018.2.Google Scholar
- 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
- 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.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.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