Ratio of two proteins may add kidneys to the transplant donor pool

August 18, 2020

Earlier this year, a study led by researchers at Johns Hopkins Medicine provided strong evidence that hundreds of deceased donor kidneys with acute kidney injury (AKI) -- traditionally discarded as unsuitable for transplantation -- could be safely and successfully used. Now, a follow-up investigation by the same team, in collaboration with researchers at 13 other medical institutions in the United States, has shown that two proteins found in deceased donor urine can be measured to define which donor organs -- including those with AKI -- are the best candidates for saving the lives of patients with kidney failure.

The team's findings were reported online July 27, 2020, by the journal Transplantation.

Currently, the national discard or rejection rate for all potential donor kidneys is approximately 18%, but for AKI kidneys, it jumps to 30%. According to statistics from the U.S. Department of Health and Human Services, nearly 100,000 Americans with kidney failure, also known as end-stage renal disease, are awaiting donor organs. Unfortunately, as reported by the U.S. Centers for Disease Control and Prevention, nearly 9,000 of these patients drop off the waiting list each year, succumbing to death or deteriorating in health so that transplantation is no longer possible.

Making matters worse, says the National Institute of Diabetes and Digestive and Kidney Diseases, the need for donor kidneys is rising at 8% per year. However, their availability has not grown to match.

To better identify which deceased donor kidneys have a higher probability for successful transplantation and long-term survival as grafted organs, the new study looked to two proteins -- both easily obtained from the urine of donors at the time of organ harvesting -- that the researchers felt could be used as clinical biomarkers.

The two proteins, uromodulin and osteopontin, had been shown in previous studies to play a protective role in kidney health and proper functioning, helping to repair cells damaged by AKI and stimulating immune responses against foreign invaders. Therefore, the research team believed that their presence in deceased donors might indicate which kidneys were most likely to recover from injuries or infections.

"We determined that if the ratio of the amounts of the two proteins, as precisely measured in samples of a deceased donor's urine, was less than or equal to three, then that person's kidneys were the most suitable for transplantation and had a higher chance for staying healthy and functioning longer after the surgery," says Chirag Parikh, M.D., Ph.D., director of the Division of Nephrology at the Johns Hopkins University School of Medicine and senior author of the study.

There were 1,298 donors and 2,430 recipients participating in the study. A total of 322 deceased donors (25%) had signs of AKI. The recipients were followed for a median time of four years after surgery to document any graft failures or deaths.

The researchers say that additional studies are needed to validate the use of the uromodulin-to-osteopontin ratio as a clinical tool for timely and accurate evaluation of kidneys for transplantation.

"We estimate that using this strategy, once confirmed as reliable, we can annually reduce the number of kidneys discarded and add a few thousand suitable-for-transplant organs to the pool," Parikh says.

Increasing the donor pool, Parikh adds, would help achieve the goal of the Advancing American Kidney Health initiative, a 2019 presidential directive that aims to double the number of kidneys available for transplant by 2030.

Johns Hopkins Medicine

Related Proteins Articles from Brightsurf:

New understanding of how proteins operate
A ground-breaking discovery by Centenary Institute scientists has provided new understanding as to the nature of proteins and how they exist and operate in the human body.

Finding a handle to bag the right proteins
A method that lights up tags attached to selected proteins can help to purify the proteins from a mixed protein pool.

Designing vaccines from artificial proteins
EPFL scientists have developed a new computational approach to create artificial proteins, which showed promising results in vivo as functional vaccines.

New method to monitor Alzheimer's proteins
IBS-CINAP research team has reported a new method to identify the aggregation state of amyloid beta (Aβ) proteins in solution.

Composing new proteins with artificial intelligence
Scientists have long studied how to improve proteins or design new ones.

Hero proteins are here to save other proteins
Researchers at the University of Tokyo have discovered a new group of proteins, remarkable for their unusual shape and abilities to protect against protein clumps associated with neurodegenerative diseases in lab experiments.

Designer proteins
David Baker, Professor of Biochemistry at the University of Washington to speak at the AAAS 2020 session, 'Synthetic Biology: Digital Design of Living Systems.' Prof.

Gone fishin' -- for proteins
Casting lines into human cells to snag proteins, a team of Montreal researchers has solved a 20-year-old mystery of cell biology.

Coupled proteins
Researchers from Heidelberg University and Sendai University in Japan used new biotechnological methods to study how human cells react to and further process external signals.

Understanding the power of honey through its proteins
Honey is a culinary staple that can be found in kitchens around the world.

Read More: Proteins News and Proteins Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.