PHILADELPHIA – In 2016, Kiran Shelat thought that he was out of options. Since receiving a diagnosis of a type of kidney disease called IgA nephropathy in 2004, he had been in and out of the hospital 19 times. To slow his disease progression, his doctors advised that he hook himself to a dialysis machine for 10 hours each night, which stretched his stomach muscles so far that he needed to undergo a hernia repair surgery. A kidney transplant could save his life, and so he was added to the waiting list, but the wait could take up to 10 years.
Later that year, a Penn Medicine physician phoned Shelat and said that he might be eligible to participate in a clinical trial in which he could receive a kidney from a deceased donor who had been infected with the hepatitis C virus (HCV). The initial THINKER trial, then led by Peter Reese, MD, a professor of Medicine and Epidemiology in the Perelman School of Medicine, and David S. Goldberg, MD, now a professor at the University of Miami, was designed to provide initial data about the safety and efficacy of transplanting kidneys from hepatitis C-positive donors. As part of the trial, Shelat would then be treated with an oral medication to cure him of the virus from the donor kidney following the transplantation.
Shelat didn’t hesitate. “I told him that was one of the most magical phone calls I ever received,” he said.
Five years after participating in the trial, Shelat says the transplant surgery has flipped his life “180 degrees.” Once too tired to climb a flight of stairs without becoming winded, the recently-retired civil engineer has taken several family vacations since 2016, including an international trip to India.
Now, with an $8 million grant from the National Institutes of Health (NIH), the next stage of the THINKER project — called THINKER-NEXT — will aim to provide a comprehensive view of the risks and benefits of transplanting HCV-infected kidneys into non-infected patients, so that success stories like Shelat’s may become routine at health systems across the country. The trial will take place for five years at eight institutions, led by Penn Medicine’s Reese, the University of Miami’s Goldberg, and Douglas E. Schaubel, PhD, a professor of Biostatistics at Penn.
“In the first stage of the trial, we found out that we could cure hepatitis C from the transplant patients. But now we want to know, how well do the organs function compared to others? Do the patients experience any unique complications? Are they susceptible to any other viruses?” Reese said. “Since this is a study that involves multiple centers, we hope to have enough data about the approach and its long-term implications. This information will be very important if we are to increase adoption of this practice across the country.
Penn Medicine and the seven collaborating institutions will transplant 200 kidneys from HCV-positive donors into new patients during the trial. They will determine: whether pursuing a HCV-positive kidney transplant improves patient survival; the one-year kidney function of HCV-positive kidney transplant recipients; whether the kidney transplant recipients have increased risks of cytomegalovirus infection; and if the prevalence of chronic kidney disease is similar in HCV-positive and HCV-negative kidney donors. The overarching goal is to determine the long-term clinical impact of transplanting kidneys from hepatitis C donors into HCV-negative patients with end-stage kidney disease.
Findings from the THINKER-NEXT project are urgently needed. Currently, the waiting list for a kidney transplant exceeds 94,000 people, with only 14,000 deceased donor kidneys available annually. For the elderly and some other patient groups, it is common to die waiting. Yet, hundreds of kidneys from donors infected with hepatitis C virus are discarded annually, and hundreds more kidneys are never procured because of the perception that that centers won’t accept them
"When the trial is over, we are optimistic that we will have enough data that supports the broad adoption of this approach into clinical practice across the country and globally,” Reese said.
For Shelat, the benefits of the surgery have far outweighed any potential risks, and he remains a vocal advocate for making HCV-positive kidney transplantation a routine clinical practice.
“For anyone who has been diagnosed with late-stage kidney disease and is looking at the dark tunnel ahead, they should know that this is an option for them,” Shelat said. “I feel better than I felt 20 years ago.”
Emily Blumberg, MD, a professor of Infectious Diseases, Roy Bloom, MD, a professor of Renal-Electrolyte and Hypertension, Stacey Prenner, MD, an assistant professor of Gastroenterology, and Peter Abt, MD, a professor of Surgery, provide expertise as co-investigators on the clinical trial. THINKER-NEXT is funded by the National Institutes of Health (1U01DK126654-01).
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