Living transplant donors need long-term monitoring, too

While organ transplant recipients receive continual care as the end-stage treatment to their condition, attention also should be given to living donors, who can suffer from hypertension, diabetes and other disorders after donation, according to a study by researchers at UC San Francisco.

As reported online April 12, 2019, in JAMA Network Open, by aggregating data from publicly available clinical studies, the researchers found that nearly one in seven kidney donors experienced a potentially adverse event that may be related to their donation.

“Our findings are significant for the transplant community,” said co-senior author Minnie Sarwal, MD, PhD, professor of surgery, medicine and pediatrics at UCSF. “We want to encourage donation, yet making the process more transparent for outcomes and safer by improved monitoring for donors, which does not exist long term, also appears to be of critical importance.”

Solid organ transplant is the preferred treatment for most end-stage organ diseases, and about 6,000 adults in the United States and 30,000 worldwide are living donors annually. However, some living kidney donors develop postoperative kidney failure and enter the organ donation system as potential recipients on the transplant waiting list, and this group also is at increased long-term risk for cardiovascular and end-stage renal disease, as well as all-cause mortality, compared to matched nondonors eligible to donate.

In the new paper, Sarwal and her colleagues analyzed 20 clinical transplant studies compiled between 1963 and 2016 and housed in ImmPort, a clinical and molecular data repository hosted by the National Institute of Allergy and Infectious Diseases, to review 9,558 donors, referring to their final data set as “ImmTransplant.” To validate the study’s accuracy, they used data collected from 1987 to 2016 and stored in the U.S. national transplant registry maintained by the Organ Procurement and Transplantation Network administered by the United Network for Organ Sharing.

While no recorded events occurred in 85.3 percent of donors, the most common adverse events were hypertension (806 cases, 8.4 percent), diabetes (190, 2 percent), proteinuria (171, 1.8 percent) and lack of bowel movements post-surgery (147, 1.5 percent). Relatively few events (269) occurred in the first two years after donation, and of the 1,746 events occurring from two to 40 years after, 1,575 cases (90.2 percent) were nonsurgical.

U.S. transplant programs are required to follow up with donors for only two years after transplant.

Further, the researchers found that living kidney donors can experience renal or cardiovascular issues that increase their likelihood of renal failure without first experiencing intermediate events. Complications or conditions soon after donation also may not be predictive of long-term renal function or vice versa. As such, long-term systematic renal monitoring and routine regular checkups for living kidney donors is recommended.

Sarwal said this study supplements ongoing research while a nationwide registry is being established to improve the recruitment, awareness, education and long-term health management of potential living donors, per an initiative launched after a June 2016 White House organ donation and transplant summit.

Demographic characteristics from the study also can provide insights into donation patterns and potential strategies to better inform living donors, said Sarwal, treasurer of The Transplantation Society, an organization whose goal is to provide global leadership in transplantation.

For example, a spike was found in living kidney donations among U.S. women whose age was in the childbearing range (age 25). As kidney donation increases the risk of hypertension and preeclampsia in pregnancies, living donors in this age range should be better informed and counseled.

“We hope these findings supplement well-informed discourse for living organ donation among potential donors, recipients, clinicians, researchers and the public,” said lead author Jieming Chen, PhD, a former postdoctoral researcher at UCSF now with Genentech. “We’ve curated the transplant datasets in ImmPort as an initial proof of concept of its utility and applications so that the collection, curation and secondary analyses of other publicly available transplant data can be built on.”

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Authors: Co-senior author Atul Butte, Sanchita Bhattacharya, Marina Sirota and Sunisa Laiudompitak, of UCSF; Henry Schaefer, of ESAC Inc.; and Elizabeth Thompson and Jeff Wiser, Northrop Grumman Information Systems Health IT.

Funding: The research was supported by the National Institute of Allergy and Infectious Diseases (ImmPort contract HHSN316201200036W), National Institute of Diabetes and Digestive and Kidney Diseases (grant R01 DK109720-02), National Library of Medicine (grant K01 LM012381), and Health Resources and Services Administration (contract 234-2005-370011C).

Disclosures: Wiser worked on ImmPort during the study and is currently employed at Medidata Solutions, but no aspect of his employment is related to the work in this manuscript. Sarwal is the founder of KITBio and Organ-I; has performed sponsored research and/or served on the scientific advisory boards for Bristol Myers Squibb, Astellas, Genentech, Immucor, Natera and Nephcure; and is affiliated with The Transplantation Society, American Society of Transplantation, International Pediatric Transplant Association, American Society of Nephrology and National Kidney Foundation. Butte reported grants and personal fees from the National Institutes of Health, the Bakar Family, and Priscilla Chan and Mark Zuckerberg during the study; grants and personal fees from Genentech, and personal fees, consisting of honoraria and travel for scientific talks, from Merck, Eli Lilly and Company, Roche, Pfizer, Bayer, American Academy of Allergy, Asthma and Immunology, American Transplant Congress, The Transplantation Society, United Network for Organ Sharing, and AbbVie outside the submitted work; personal fees from NuMedii, where he is also founder, consultant and shareholder, and where his spouse serves as CEO, outside the submitted work; and he owns shares in Google, Microsoft, Apple, Amazon, Facebook and CVS.

About UCSF: UC San Francisco (UCSF) is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy; a graduate division with nationally renowned programs in basic, biomedical, translational and population sciences; and a preeminent biomedical research enterprise. It also includes UCSF Health, which comprises three top-ranked hospitals – UCSF Medical Center and UCSF Benioff Children’s Hospitals in San Francisco and Oakland – as well as Langley Porter Psychiatric Hospital and Clinics, UCSF Benioff Children’s Physicians and the UCSF Faculty Practice. UCSF Health has affiliations with hospitals and health organizations throughout the Bay Area. UCSF faculty also provide all physician care at the public Zuckerberg San Francisco General Hospital and Trauma Center, and the SF VA Medical Center. The UCSF Fresno Medical Education Program is a major branch of the University of California, San Francisco’s School of Medicine. Please visit http://www.ucsf.edu/news.