Preformed Antibodies Put Kidney Transplant Recipients at Risk
New research could provide better donor-recipient matches and tailor recipients' treatments after kidney transplantation.
-- by Alexia Severson
Kidney transplant recipients with even very low levels of preformed antibodies directed against a donated kidney have a higher risk of organ rejection and kidney failure, according to a new study published in the Journal of the American Society of Nephrology.
An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens, such as bacteria, fungi, parasites, and viruses. While antibodies are normally meant to protect our bodies, transplant recipients who’ve had previous transplants, blood transfusions, and other sensitizing events often have antibodies directed against a particular donor's kidney.
The level at which these antibodies put transplant recipients at risk has remained unclear based on traditional tests. However, the development of new tests, called solid phase assays, allows researchers to detect preformed antibodies at much lower blood concentrations than ever before.
The Expert Take
To find out the degree to which certain antibodies put transplant recipients at risk, Sumit Mohan, M.D., Amudha Palanisamy, M.D., and their colleagues at the Columbia University Medical Center examined the health outcomes of kidney transplant recipients with preformed donor-specific antibodies.
They found that the detection of donor-specific antibodies by newer tests, despite negative results from older tests, nearly doubles the risk for antibody-mediated rejection and increases the risk of kidney failure by 76 percent. The absolute risk of failure in the first year in the United States is currently about 8.2 percent for first-time recipients and about 10.7 percent for repeat transplant recipients.
"Our study quantifies the level of risk associated with antibodies detected at the time of transplantation, helping clinicians better understand the prognosis and the risk of failure, thereby allowing for appropriate tailoring of immunosuppressive therapy," said Mohan.
These findings suggest donor selection processes should take into consideration the presence of antibodies in the recipient, as identified by newer, more sensitive tests, researchers concluded.
Source and Method
To help them in their research, Mohan, Palanisamy, and their colleagues used medical literature to find studies that looked at the health outcomes of kidney transplant recipients with preformed donor-specific antibodies.
The team searched PubMed and the Cochrane database using specific search phrases, as well as hand-searching archived abstracts presented at the American Society of Nephrology and the American Transplant Congress meetings between 2005 and 2010 for reported studies that were not subsequently published as full manuscripts in the peer reviewed literature.
They identified seven studies that included 1,119 patients for this study.
According to kidneylink.org, there were over 15,000 kidney transplants were performed in the U.S. in 2006. Living kidney donations have been proven to provide better patient outcomes and increased kidney survival compared to deceased kidney donation.
The findings in this study could help future patients in need of a kidney transplant find better donor-recipient matches, as well as allow doctors to tailor recipients' treatments after kidney transplantation.
A study published in 2004 in Transplant Immunology also looked at the risk of donor-specific antibodies, but with a focus on heart and lung transplantation. Researchers in this study found that heart and lung recipients transplanted in the presence of donor-specific antibodies are also at an increased risk for early acute rejection and have a lower graft survival. They concluded that the presence and level of donor-specific antibodies is crucial to survival outcomes, and allows for measurement of efficient therapeutic techniques.
In another study published in the American Journal of Transplantation in 2009, researchers described the clinical relevance of subclinical antibody-mediated rejection (SAMR) in a cohort of 54 DSA-positive kidney transplant recipients receiving a deceased donor. They found that SAMR at three months was associated with worse glomerular and tubulointerstitial scarring after one year.
A study published in The New England Journal of Medicine in 2007 determined whether an immune response to major-histocompatibility-complex (MHC) class I-related chain A (MICA) antigens—which can elicit antibody production—play a role in the failure of kidney allografts. Researchers concluded that pre-sensitization of kidney-transplant recipients against MICA antigens is associated with an increased frequency of graft loss.