NEJM: Research uncovers potential to increase number of kidney transplants
Research led by Dr. Midhat Farooqi of Children's Mercy and several others
Waiting times for kidney transplants exceed 3 to 5 years in many parts of the United States. Yet more than 500 high-quality kidneys from deceased donors with hepatitis C virus (HCV) infection are discarded annually. Direct-acting antiviral agents, which are associated with high HCV cure rates and manageable side effects, have created the potential to substantially increase the number of kidney transplants by making HCV-infected kidneys available to HCV-negative candidates on the waiting list.
In this open-label, single-group, pilot trial at the University of Pennsylvania, we sought to determine the safety and efficacy of transplantation of kidneys from HCV genotype 1–viremic donors into HCV-negative patients, followed by elbasvir–grazoprevir (Zepatier) treatment. An external data and safety monitoring board reviewed all aspects of the trial. The authors vouch for the completeness and accuracy of the data and analysis and for the adherence of the trial to the protocol, available with the full text of this letter at NEJM.org.
Adults who were undergoing dialysis and who had long anticipated waiting times for a kidney transplant were eligible for inclusion in the trial, and patients with conditions that substantially elevate the risks of liver disease, allograft failure, or death were excluded. A physician-led, three-step, informed-consent process was implemented.
Deceased-donor criteria ensured selection of high-quality kidneys. Since elbasvir–grazoprevir is not approved by the Food and Drug Administration (FDA) for patients with HCV genotypes 2 or 3, and a direct-acting antiviral agent for the treatment of patients with those genotypes who have renal failure has not been approved by the FDA, donors were limited to those who had positive qualitative HCV nucleic acid test results and HCV genotype 1. We developed a new protocol for donor genotyping concurrent with organ allocation.
Intravenous glucocorticoids and rabbit antithymocyte globulin were administered to all recipients, followed by oral tacrolimus, mycophenolate mofetil, and prednisone. The HCV viral load was measured in recipients on postoperative day 3; elbasvir–grazoprevir was initiated when the results became positive, and therapy was maintained for 12 weeks.
Read the full article via The New England Journal of Medicine.