Possible Tissue Injury Predictor in Transplant Recipients Found

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Researchers may have discovered a predictor for focal segmental glomerulosclerosis (FSGS), a disorder that can accelerate organ failure in kidney transplant recipients, according to a study published in Science Translational Medicine. To identify potential FSGS predictors, researchers used high-density protein tests to process 141 serum samples from 98 kidney patients (64 with FSGS) before and 1 year after transplant surgery.

They screened for approximately 9,000 antigens. In patients at risk for FSGS, antibodies against 789 antigens were significantly increased. The researchers conducted further studies using mice and found the antibody levels in a protein called CD40 predicted FSGS with 78% accuracy. A panel of seven out of 10 antibodies that target glomerular antigens increased accuracy to 92%.

These results led the researchers to develop a pre-transplant antibody panel that includes anti- CD40 antibodies called FSGS Antibody Screen for Transplant (FAST). FAST led the researchers to discover that antibody signatures in FSGS patients remain 1 year after transplant, despite intensified immunosuppressive therapy and plasma exchange. Researchers noted that the antibody binding to the CD40 protein spurs injury to the kidney’s filtering unit, and blocking this antibody appears to reverse damage.

This suggests blocking CD40 in kidney transplant patients could help cure FSGS. This discovery could eventually help the development of customized therapies and improved patient selection for transplant.

FSGS: Talking Points for the Practicing Nephrologist
A predictor for focal segmental glomerulosclerosis (FSGS) in kidney transplant recipients.

Researchers at UC San Francisco and Rush University Medical Center, Chicago, may have found a predictor for a disorder affecting kidney transplant recipients that can accelerate organ failure, a discovery that eventually could allow for customized therapies and improved patient selection for transplant. The study of focal segmental glomerulosclerosis (FSGS), a devastating form of kidney disease, is in the Oct. 1 issue of Science Translational Medicine.

Research was conducted by an international study team, with Necker Hospital in Paris and UCSF joint lead authors and Rush University Medical Center and UCSF joint senior authors. “This is a new blood test to monitor patients before kidney transplant and predict who may have recurrence of FSGS, thereby preventing loss of kidneys,” said co-senior author Minnie Sarwal, MD, PhD, professor of transplant surgery at UCSF.

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