Biopsy Kidneys From Live Donors to Predict Transplant Success

Pam Harrison

February 03, 2020

Subclinical structural features in kidneys from living donors that can only be seen with a microscope modestly contribute to predicting the long-term success of a transplant, new research suggests.

In an analysis that involved 2293 living donor-recipient pairs, intraoperative biopsy of the renal cortex of the donated kidney was performed to identify factors that predicted future graft failure — independent of donor and recipient risk factors, including age and kidney function.

These came down to interstitial fibrosis/tubular atrophy, larger cortical nephron size (although not nephron number), and smaller medullary volume.

"We think that these subtle abnormalities in the living kidney donor may make the kidney more susceptible to fail in the future in recipients," lead investigator Naim Issa, MD, Mayo Clinic, Rochester, Minnesota, said in a statement from his institution. The study was published online January 23 in the Journal of the American Society of Nephrology.

"These important findings may provide insights into unrecognized predictors of kidney transplant failure in recipients," Issa added.

However, he and his colleagues stress that even if these subtle structural abnormalities are detected in a living donor kidney, the findings should not deter anyone's decision to donate his or her kidney to a patient who needs one.

Patients who receive a live donor kidney generally have better outcomes than those who receive a deceased donor organ, largely because kidneys from living donors tend to last longer than those from deceased donors.

Aging Kidney Anatomy Study

In the United States last year, nearly 7400 living donor transplants were performed, according to the United Network for Organ Sharing; it was a record year for living organ donation in the US but still a far cry from the nearly 95,000 organs needed for patients who are still awaiting a donor kidney.

Living kidney donation has become the preferred therapeutic option for patients with end-stage renal disease. A thorough clinical evaluation with laboratory testing is required to ensure the donor has healthy kidneys.

Despite this, certain live donor clinical characteristics (particularly older age and lower glomerular filtration rate) predict an increased risk of death-censored graft failure in the recipient.  

These clinical characteristics may reflect underlying structural features in the kidney that are predictive of longevity of the graft, so the researchers set out to examine kidney structural predictors of death-censored graft failure.

The study took place in 3 transplant centers involved in the Aging Kidney Anatomy study — donor and recipient pairs at Mayo Clinic Minnesota (n = 1585), Mayo Clinic Arizona (n = 436), and Cleveland Clinic in Ohio (n = 272) — examining organs donated between May 1999 and December 2017.

"All kidney donors underwent a thorough medical evaluation prior to donation that included a prescheduled series of tests," including a CT scan, the researchers note. And an intraoperative needle core biopsy of the renal cortex of the donated kidney was performed during transplantation.

During follow-up, 12.5% of recipients developed death-censored graft failure and 18.5% of donor recipients died.

The mean time to death-censored graft failure or last follow-up was 6.3 years, the authors note.

"Each kidney structural feature on biopsy or CT scan at the time of transplantation was evaluated as a predictor of death-censored graft failure," they explain.

Findings Support Biopsies to ID Grafts at Higher Risk of Failure

After adjusting for both donor and recipient clinical characteristics, the structural features that appeared to affect the life span of a posttransplant kidney were the percentage of interstitial fibrosis/tubular atrophy (IF/TA) in the allograft (an IF/TA >5%); arteriolar hyalinosis as detected by the pathologist on biopsy slides; larger glomeruli and tubules; and smaller medulla at the time of donation.

These all modestly predicted for death-censored graft failure, the authors elaborate.

"[These findings] provide important insights into the factors that define the 'intrinsic quality' of the living kidney donor graft at the time of donation and support the use of intraoperative biopsies to identify kidney allografts that are at higher risk for failure," they emphasize.

The investigators point out that intraoperative kidney biopsy has very low risk for harm, with any bleeding easily controlled by the surgeon.

However, they reiterate that even with the abnormalities detected on biopsy,

"Availability of a willing person with acceptable health for kidney donation will generally supersede concerns regarding graft quality."

"And if the biopsy shows arteriolar hyalinosis, IF/TA >5% or enlarged nephrons...[transplant recipients] may benefit from non-CNI (calcineurin inhibitor)-based immunosuppression or more aggressive management of blood pressure to prevent worsening arteriolar hyalinosis or nephron enlargement," they indicate.

However, the researchers also caution, "Further studies are needed to determine if recipient management benefits from modifications based on the living donor biopsy findings."

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. The authors have disclosed no relevant financial relationships.

J Amer Soc Nephrol. Published online January 23, 2020. Abstract

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