Peter P. Reese, MD, MSCE; Peter L. Abt, MD; Emily A. Blumberg, MD; Vivianna M. Van Deerlin, MD, PhD; Roy D. Bloom, MD; Vishnu S. Potluri, MD, MPH; Matthew Levine, MD, PhD; Paige Porrett, MD, PhD; Deirdre Sawinski, MD; Susanna M. Nazarian, MD, PhD; Ali Naji, MD, PhD; Richard Hasz, BS, MFS; Lawrence Suplee, MS; Jennifer Trofe-Clark, PharmD; Anna Sicilia, BS; Maureen McCauley, BA; Caren Gentile, MS; Jennifer Smith, BS; Bijan A. Niknam, BS, BA; Melissa Bleicher, MD; K. Rajender Reddy, MD; David S. Goldberg, MD, MSCE
Disclaimer: The data reported in this article have been supplied by the United Network for Organ Sharing as the contractor for OPTN. The interpretation and reporting of these data are the responsibility of the authors and should in no way be seen as an official policy of or interpretation by the OPTN or the U.S. government. The Health Resources and Services Administration, U.S. Department of Health and Human Services, oversees the activities of the OPTN contractor.
Acknowledgment: The authors gratefully acknowledge the extensive efforts of staff from the Gift of Life Donor Program (Philadelphia, Pennsylvania) and other organ procurement programs that helped coordinate information about organ donors and HCV genotype specimen collection. They also acknowledge the remarkable efforts of staff at the Molecular Pathology Laboratory at the Hospital of the University of Pennsylvania, who implemented a rapid HCV genotyping method that is available 24 hours a day, 7 days a week. Many transplant staff members at the University of Pennsylvania also made important contributions to the care of THINKER patients. The authors thank Jeff Silber, MD, PhD; Paul Rosenbaum, PhD; and James Sharpe, MS, for assistance with matching and Jane Kearns, MT (ASCP), CHS, for full interpretation of HLA and donor-specific antibody data. The authors also thank the THINKER trial participants and recognize the generosity of the organ donors and their families.
Financial Support: The study was sponsored by a grant from Merck to the University of Pennsylvania. Merck provided funds for study activities as well as elbasvir–grazoprevir. The study also received funding from the Fred and Suzanne Biesecker Foundation at the Children's Hospital of Philadelphia. Dr. Potluri was supported by a Ben J. Lipps research grant from the American Society of Nephrology. The authors maintained full control over data collection, analysis, and interpretation. Drs. Goldberg and Reese led all analyses and take full responsibility for the quality of the data.
Disclosures: Dr. Reese reports grants from Merck, CVS Caremark, AstraZeneca, and Bristol-Meyers Squibb and other financial support from the American Journal of Kidney Diseases outside the submitted work. Dr. Blumberg served on an advisory board for Merck outside the submitted work. Dr. Bloom reports other financial support from Merck, AbbVie, Veloxis, CSL Behring, and UpToDate and grants from CareDx, Veloxis, and Shire outside the submitted work. Dr. Levine reports nonfinancial support from Pfizer outside the submitted work. Dr. Sawinski reports other financial support from Merck outside the submitted work. Dr. Reddy reports grants from AbbVie during the conduct of the study; grants from Gilead, Bristol-Meyers Squibb, Merck, Vertex, Janssen, Conatus, Intercept, and Mallinckrodt outside the submitted work; personal fees from Gilead, AbbVie, Vertex, Bristol-Meyers Squibb, Janssen, Merck, Shionogi, and Dova outside the submitted work; and royalties from UpToDate. Dr. Goldberg reports grants and personal fees from Merck outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-0749.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol: See . Statistical code: Available from Dr. Reese (e-mail, email@example.com). Data set: Deidentified elements of the study data set will be shared with investigators, with case-by-case review to ensure confidentiality of participants (e-mail, firstname.lastname@example.org).
Corresponding Author: Peter P. Reese, MD, MSCE, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, 917 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104; e-mail, email@example.com.
Current Author Addresses: Dr. Reese: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, 917 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104.
Drs. Abt, Bloom, Potluri, Levine, Porrett, Sawinski, Nazarian, Naji, and Bleicher: Perelman School of Medicine, University of Pennsylvania, One Founders Pavilion, 3400 Spruce Street, Philadelphia, PA 19104.
Dr. Blumberg: Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, 3 Silverstein, Suite E, 3400 Spruce Street, Philadelphia, PA 19104.
Dr. Van Deerlin: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, 7.103 Founders Pavilion, 3400 Spruce Street, Philadelphia, PA 19104.
Mr. Hasz and Mr. Suplee: Gift of Life Donor Program, 401 North 3rd Street, Philadelphia, PA 19123.
Dr. Trofe-Clark: Perelman Center for Advanced Medicine, West Pavilion, 2nd Floor, 3400 Civic Center Boulevard, Philadelphia, PA 19104.
Ms. Sicilia and Ms. McCauley: Perelman School of Medicine, University of Pennsylvania, 729 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104.
Ms. Gentile and Ms. Smith: Molecular Pathology Laboratory, Department of Pathology and Laboratory Medicine, University of Pennsylvania Health System, 3400 Spruce Street, Philadelphia, PA 19104.
Mr. Niknam: Center for Outcomes Research, The Children's Hospital of Philadelphia, 2716 South Street, Room 5121, Philadelphia, PA 19146.
Dr. Reddy: Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, 2 Dulles, 3400 Spruce Street, Philadelphia, PA 19104.
Dr. Goldberg: Perelman School of Medicine, University of Pennsylvania, 730 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104.
Author Contributions: Conception and design: P.P. Reese, P.L. Abt, E.A. Blumberg, V.M. Van Deerlin, R.D. Bloom, D. Sawinski, L. Suplee, M. McCauley, M. Bleicher, K.R. Reddy, D.S. Goldberg.
Analysis and interpretation of the data: P.P. Reese, E.A. Blumberg, R.D. Bloom, V.S. Potluri, M. Levine, R. Hasz, J. Trofe-Clark, C. Gentile, B.A. Niknam, M. Bleicher, K.R. Reddy, D.S. Goldberg.
Drafting of the article: P.P. Reese, P.L. Abt, E.A. Blumberg, R.D. Bloom, V.S. Potluri, M. Bleicher, D.S. Goldberg.
Critical revision of the article for important intellectual content: P.P. Reese, P.L. Abt, E.A. Blumberg, V.M. Van Deerlin, R.D. Bloom, V.S. Potluri, M. Levine, D. Sawinski, S.M. Nazarian, J. Trofe-Clark, B.A. Niknam, M. Bleicher, K.R. Reddy, D.S. Goldberg.
Final approval of the article: P.P. Reese, P.L. Abt, E.A. Blumberg, V.M. Van Deerlin, R.D. Bloom, V.S. Potluri, M. Levine, P. Porrett, D. Sawinski, S.M. Nazarian, A. Naji, R. Hasz, L. Suplee, J. Trofe-Clark, A. Sicilia, M. McCauley, C. Gentile, J. Smith, B.A. Niknam, M. Bleicher, K.R. Reddy, D.S. Goldberg.
Provision of study materials or patients: P.L. Abt, M. Levine, P. Porrett, S.M. Nazarian, R. Hasz, M. McCauley.
Statistical expertise: P.P. Reese, V.S. Potluri, B.A. Niknam, D.S. Goldberg.
Obtaining of funding: P.P. Reese, D.S. Goldberg.
Administrative, technical, or logistic support: P.P. Reese, P.L. Abt, R.D. Bloom, P. Porrett, D. Sawinski, L. Suplee, A. Sicilia, C. Gentile, J. Smith, B.A. Niknam, M. Bleicher, D.S. Goldberg.
Collection and assembly of data: P.P. Reese, V.M. Van Deerlin, V.S. Potluri, M. Levine, P. Porrett, R. Hasz, A. Sicilia, M. McCauley, C. Gentile, M. Bleicher, D.S. Goldberg.
Organs from hepatitis C virus (HCV)–infected deceased donors are often discarded. Preliminary data from 2 small trials, including THINKER-1 (Transplanting Hepatitis C kidneys Into Negative KidnEy Recipients), suggested that HCV-infected kidneys could be safely transplanted into HCV-negative patients. However, intermediate-term data on quality of life and renal function are needed to counsel patients about risk.
To describe 12-month HCV treatment outcomes, estimated glomerular filtration rate (eGFR), and quality of life for the 10 kidney recipients in THINKER-1 and 6-month data on 10 additional recipients.
Open-label, nonrandomized trial. (ClinicalTrials.gov: NCT02743897)
20 HCV-negative transplant candidates.
Participants underwent transplant with kidneys infected with genotype 1 HCV and received elbasvir–grazoprevir on posttransplant day 3.
The primary outcome was HCV cure. Exploratory outcomes included 1) RAND-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) quality-of-life scores at enrollment and after transplant, and 2) posttransplant renal function, which was compared in a 1:5 matched sample with recipients of HCV-negative kidneys.
The mean age of THINKER participants was 56.3 years (SD, 6.7), 70% were male, and 40% were black. All 20 participants achieved HCV cure. Hepatic and renal complications were transient or were successfully managed. Mean PCS and MCS quality-of-life scores decreased at 4 weeks; PCS scores then increased above pretransplant values, whereas MCS scores returned to baseline values. Estimated GFRs were similar between THINKER participants and matched recipients of HCV-negative kidneys at 6 months (median, 67.5 vs. 66.2 mL/min/1.73 m2; 95% CI for between-group difference, −4.2 to 7.5 mL/min/1.73 m2) and 12 months (median, 72.8 vs. 67.2 mL/min/1.73 m2; CI for between-group difference, −7.2 to 9.8 mL/min/1.73 m2).
Twenty HCV-negative recipients of HCV-infected kidneys experienced HCV cure, good quality of life, and excellent renal function. Kidneys from HCV-infected donors may be a valuable transplant resource.
Flow chart of recruitment, enrollment, and follow-up of study participants.
Data are as of 28 June 2017, the date of the 20th kidney transplant. Between the completion of THINKER-1 and the end of THINKER-2, 12 additional patients were prescreened and 41 who had been excluded because they were not receiving dialysis subsequently started dialysis, but among these 53 patients, 25 were newly recognized to have other reasons for exclusion. FSGS = focal segmental glomerulosclerosis; HBV = hepatitis B virus; HCV = hepatitis C virus; PRA = panel reactive antibody; THINKER = Transplanting Hepatitis C kidneys Into Negative KidnEy Recipients.
* Participants met criteria for blood type, age, and priority based on waiting time or time on dialysis on the kidney transplant waitlist at our institution.
Table 1. Characteristics of Kidney Transplant Recipients in the THINKER Study (n = 20)
HCV viral load detected by polymerase chain reaction among kidney transplant recipients (n = 18) and their deceased donors (n = 13).
Five donors each had 2 kidneys recovered for THINKER participants (circles). The other 8 donors each had 1 kidney recovered for a THINKER participant (squares). The last 2 donors had detectable HCV on qualitative nucleic acid testing but insufficient samples to obtain a quantitative HCV viral load (not shown). Donor and recipient HCV RNA levels were strongly correlated. In a linear regression model, the β-coefficient was 0.95 (95% CI, 0.60 to 1.31; P < 0.001), meaning that the slope of the line is close to 1. HCV = hepatitis C virus; THINKER = Transplanting Hepatitis C kidneys Into Negative KidnEy Recipients.
Trajectories of PCS, MCS, and domain scores over time among 20 HCV-negative recipients of HCV-infected kidneys.
Vertical lines represent when surveys were conducted. Twenty patients were analyzed at the screening visit (week 0), 19 were analyzed at 24 wk, and 10 were analyzed at 52 wk. HCV = hepatitis C virus; MCS = Mental Component Summary; PCS = Physical Component Summary; THINKER = Transplanting Hepatitis C kidneys Into Negative KidnEy Recipients.
Table 2. Comparison of eGFRs and Creatinine Levels at 6 and 12 Months Between THINKER Participants and Matched Comparator Recipients of Kidneys From HCV-Negative Donors
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Reese PP, Abt PL, Blumberg EA, Van Deerlin VM, Bloom RD, Potluri VS, et al. Twelve-Month Outcomes After Transplant of Hepatitis C–Infected Kidneys Into Uninfected Recipients: A Single-Group Trial. Ann Intern Med. ;169:273–281. doi: 10.7326/M18-0749
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Published: Ann Intern Med. 2018;169(5):273-281.
Published at www.annals.org on 7 August 2018
Gastroenterology/Hepatology, Hospital Medicine, Infectious Disease, Liver Disease, Nephrology.
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