Better Predictors for Graft Failure in Kidney Recipients

Naim Issa, MD

There is currently little known about the influence of a donated kidney’s structural features on the recipient's risk of death-censored graft failure.

A multi-institutional team, led by Naim Issa, MD, Division of Nephrology and Hypertension, William J von Liebig Center for Transplantation and Clinical Regeneration, used computed tomography (CT) and implantation biopsies to examine donated kidney features as predictors of death-censored graft failure at 3 transplant centers participating in the Aging Kidney Anatomy study.

The quality of a kidney from a living doctor is generally inferred from the donor’s age, risk factors, and kidney function. Nephrosclerosis, nephron size, and nephron number can vary among kidneys transplanted from living donors, but whether these structural features predict kidney transplant recipient outcomes is not known.

The team conducted an analysis of 2293 kidney donor-recipient pairs to identify subclinical nephrosclerosis, larger nephron size, but not nephron number, as well as the smaller medullary volume as structural predictors of death-censored graft failure that were independent of both donor and recipient clinical characteristics.

They used global glomerulosclerosis, interstitial fibrosis/tubular atrophy, artery luminal stenosis, and arteriolar hyallinoisis to measure nephrosclerosis, mean glomerular volume, cortex volume per glomerulus, and mean cross-sectional tubular area to measure nephron size, and calculations from CT cortical volume and glomerular density on biopsy to assess nephron number.

The investigators also determined the death-censored risk of graft failure with each structural feature after adjusting for the predictive clinical characteristics of donor and recipient.

The mean recipient follow-up was 6.3 years, where 287 death-censored graft failures and 424 deaths occurred.

Factors that predicted death-censored graft failure independent of both donor and recipient clinical characteristics, included interstitial fibrosis/tubular atrophy, larger cortical nephron size but not nephron number, and smaller medullary volume.

“Subclinical nephrosclerosis, larger cortical nephron size, and smaller medullary volume in healthy donors modestly predict death-censored graft failure in the recipient, independent of donor or recipient clinical characteristics,” the authors wrote. “These findings provide insights into a graft’s 'intrinsic quality’ at the time of donation, and further support the use of intraoperative biopsies to identify kidney grafts that are at higher risk for failure.”

One of the ways investigators are hoping to expand the donor pool is by including discarded kidneys.

Recent data suggests the transplant community should expand their use of deceased donor acute kidney injury (AKI) kidneys and investigator whether currently discarded AKI kidneys can be effectively used.

A team led by Caroline Liu, MHS, Division of Nephrology, Department of Medicine, The Johns Hopkins University School of Medicine, examined whether deceased donor AKI associated with recipient graft survival after matching on deceased donor acute kidney injuries propensity.

The investigators examined a total of 6832 deceased donors with AKI and 15,310 deceased donors without AKI who had at least 1 kidney transplanted in the US, from 2010-2013.

The investigators found the recovery and transplantation of AKI kidneys varied by organ procurement organization, with 39 of 58 organizations reporting high recovery and high discard rates of AKI kidneys. Approximately 98% of the donors with AKI were matched to deceased donors without AKI.

Deceased donor AKI status had no association with death-censored graft failure (HR, 1.01; 95% CI, .95-1.08) or all-cause graft failure (HR, .97; 95% CI, .93-1.02) and the results were consistent after examining by AKI stage and adjusting for recipient and transplant characteristics.

The study, “Kidney Structural Features from Living Donors Predict Graft Failure in the Recipient,” was published online in the Journal of the American Society of Nephrology.