Advancing the Science

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November 12, 2020

New research shows markers in donor kidneys that could reduce risks

By Advancing the Science contributor
Medical illustration of living kidney donation

By Jay Furst

The donation of a kidney to a person in need of a transplant is one of the most profound gifts a person can offer. The process for living kidney donors is safe, and, at Mayo Clinic, which has one of the largest living-donor kidney transplant programs in the U.S., the process is rigorous in assessing and protecting the donor's health.

A very small number of living donors develop chronic kidney disease or low renal function years after donation, and Mayo researchers have been looking for clues to determine why this occurs. A CT scan can detect some abnormalities in the kidney prior to donation, but often it's unclear whether they're significant. Biopsies aren't routinely done prior to transplant, so in the rare cases of development of chronic kidney disease after donation, it's unclear whether it's related to the donor's preexisting condition or health changes later.

Mayo Clinic has a rich resource of kidney biopsy material in its Aging Kidney Anatomy Study, led by Andrew Rule, M.D., a Mayo Clinic nephrologist. A new study of living kidney donors at Mayo Clinic in Minnesota and Arizona from 1999 to 2018 has found some microstructural features that can indicate some long-term susceptibility for chronic kidney disease in otherwise healthy adults.

The study, published in Mayo Clinic Proceedings, reinforces that kidney donation is safe for living donors, and it provides new insights for counseling donors on how to take care of themselves and preserve kidney function, according to Naim Issa, M.D., a Mayo Clinic transplant nephrologist.

"We owe it to all living kidney donors to find any information that could help minimize risk of losing kidney function decades after donation."

NAIM ISSA, M.D., TRANSPLANT NEPHROLOGIST

"We owe it to all living kidney donors to find any information that could help minimize risk of losing kidney function decades after donation," Dr. Issa says. "We believe this information can be extremely helpful for clinicians to identify certain living donors at the time of donation and counsel them about lifelong healthy living."

The study reviewed the cases of 807 people who donated kidneys between May 1, 1999, and Dec. 31, 2018, and who then responded to mail survey and telephone interviews conducted by the Mayo Clinic Survey Research Center. The mean time after donation was 10.5 years.

Based on kidney biopsies from the time of donation and on information gained from the survey, researchers found two microstructural changes in particular that may indicate a possible long-term risk, says Massini Merzkani, M.D., the study's first author. One of the changes involves the nephrons, tiny structures in the kidney that remove excess fluid and waste material from your blood. The other involves the glomeruli, filters inside the nephrons that remove waste products while passing on the substances your body needs, such as sodium and potassium.

"The main discovery is that a decade after donating a kidney, living donors with low nephron numbers for their age were at higher risk of developing lower kidney function from their pre-donation level," says Dr. Merzkani. "Donors with enlarged glomeruli also were at risk of developing lower kidney function and abnormal protein spilling in the urine, which is a marker of kidney disease."

These features, not evident with standard, noninvasive donor evaluations, may indicate a risk of future kidney disease or declining kidney function.

"Reassuringly, we did not have any donors who had kidney disease that would require a transplantation or dialysis, which speaks to the careful evaluation and screening of potential donors, to assure that donors are in excellent health and are appropriate candidates for donation," Dr. Issa says.

The Mayo research team led by Dr. Rule examined the microstructural features of the kidney biopsies taken at the time of donation and assessed them as predictors of hypertension and kidney function that the patients may have developed later. The Mayo team expected to find that the size of the nephrons and a lower number of nephrons would be predictive of lower kidney function later. The enlargement of nephrons typically means that they are under some metabolic stress.

"What is reassuring is that our findings support the notion that living kidney donation is safe."

NAIM ISSA, M.D.

"What is reassuring is that our findings support the notion that living kidney donation is safe," Dr. Issa says. "Living kidney donors are examined exhaustively in advance to ensure that they are in good health and don't have any medical condition that precludes donation or puts their future health at risk, so this is not a surprise. But these findings provide insights into counseling donors on preserving future kidney function and health, such as paying attention to weight gain and hypertension."

Dr. Issa says he's aware of only one other study that looks at microstructural features in the kidney of living donors as a predictor of long-term kidney function. The results of this much larger Mayo study were consistent with the earlier research, but more research is needed, with a larger sample size and greater racial diversity among the donors. One goal would be to find less invasive methods, such as a blood test, to detect these abnormalities in the kidneys of potential donors.

More information on these abnormalities clearly is relevant to the transplant recipient as well as the living donor. "These subtle subclinical features may progress and lead to problems for the transplant patient later," Dr. Issa says. "The more information we have in advance, the more assurance we can have for the donor and recipient."

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This study was made possible by several federal funding awards, and supported by Mayo Clinic Center for Clinical and Translational Science.

Editor's Note: At the time of the study, the first author, Massini Merzkani, M.D., was a transplant nephrology fellow at Mayo Clinic. He has since relocated to practice at Washington University School of Medicine in St. Louis. 

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Tags: Andrew Rule, biopsy, Center for Clinical and Translational Science, clinical research, Findings, kidney disease, kidney transplant, living donor, Massini Merzkani, Mayo Clinic Proceedings, Naim Issa, News

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