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Presence of antibody in deceased kidney donors tied to graft failure
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A study done by researchers from the Netherlands has tied greater risk of allograft loss in kidney transplants with one protein found in deceased donor kidneys.
However, autoantibodies against Rho GDPdissociation inhibitor 2 (ARHGDIB), one of the 14 proteins reviewed in the study, only had an impact among deceased donor kidneys, not living-related kidneys, wrote Elena G. Kamburova, MD, of Utrecht University, and colleagues from other medical centers in the Netherlands.
“We suggest that pretransplant risk assessment can be improved by measuring antiARHGDIB antibodies in all patients awaiting deceaseddonor transplantation,” the authors wrote.
The clinical significance of nonhuman leukocyte antigen (HLA) antibodies on renal allograft survival has previously been under debate, the authors noted, “due to differences in reported results and lack of largescale studies incorporating analysis of multiple nonHLA antibodies simultaneously.”
While kidney transplantation is the preferred treatment over dialysis for those with ESKD and has experienced improved outcomes with allograft survival, “antibodymediated rejection (ABMR) remains one of the major causes of graft loss and of deterioration of graft function in the longterm. Donorspecific antiHLA antibodies (DSAs) are well known to play an important role in this process.
“Nonetheless, (subclinical) ABMR occurs also in the absence of DSA, which has sparked interest in the short and long-term clinical relevance of donor reactive antibodies recognizing proteins other than HLA (ie, nonHLA antibodies),” the authors wrote.
To test the impact of various proteins on allograft survival, researchers developed a multiplex nonHLA antibody assay against 14 proteins seen in the kidney. Of the 6,097 kidney transplantations with a negative complementdependent cytotoxicity crossmatch performed between January 1995 and December 2005 (Dutch Organ Transplant Registry data), the assay created by the researchers was tested in 4,770 recipients transplanted between 1995 and 2006.
Multivariable analysis showed the presence of ARHGDIB antibodies was associated with a greater risk of 10year graft failure with 3,276 deceased donor kidney transplants. The assay was tested in 1,496 recipients of living donor kidneys, and “the presence of ARHGDIB antibodies was not associated with decreased graft survival or increased risk of graft failure,” the authors noted.
Researchers did not find any significant graft loss for the other 13 nonHLA antibodies.
“It is currently unknown whether the presence of these antibodies is a biomarker, as is the case in many autoimmune diseases, or whether they play a role in the pathogenesis of graft loss,” the authors concluded. “Although validation of our findings in independent cohorts is necessary, based on these results, we suggest that pretransplant risk assessment can be improved by measuring these antibodies in all patients awaiting deceaseddonor transplantation.” – by Mark E. Neumann
Disclosures: The authors reported no relevant financial disclosures.
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