1. C1q-binding donor-specific anti-HLA antibodies predicted worse graft survival in kidney transplant patients.
2. Inclusion of C1q-binding donor-specific anti-HLA antibodies improved risk stratification.
Evidence Rating Level: 2 (Good)
Study Rundown: This study demonstrated that donor-specific anti-HLA antibodies were heterogeneous and that their ability to bind complement significantly impacted kidney-allograft survival. This is not surprising, as antibody-mediated activation of the complement system represents one of the main mechanisms for allograft injury, together with T-cell mediated cytotoxicity. The study concluded that including the presence of complement-binding antibodies improved discrimination capacity and continuous net reclassification in the reference model. These results highlight the need for therapies targeting complement to improve survival in patients with complement-binding anti-HLA antibodies. The study has a strong design with over 1000 subjects and is well-controlled for subgroup differences, especially populations across the two transplant centers in Paris.
Relevant Reading: Rejection of the Kidney Allograft
In-Depth [prospective cohort study]: This study sought to determine whether C1q-binding donor-specific anti-HLA antibodies had any predictive power in kidney-allograft survival. Patients with C1q-binding donor-specific anti-HLA antibodies had a lower eGFR at 1 year (42±22 ml/min) than did patients with non-C1q-binding donor-specific anti-HLA antibodies (51±20 ml/min) and patients without such antibodies (54±19 ml/min). C1q-binding donor-specific anti-HLA antibodies were also associated with the worst 5-year graft survival rate (54%), as compared to patients with non-C1q-binding donor-specific anti-HLA antibodies and those without such antibodies (93% and 94%, respectively; P<0.001 for both comparisons).
Multivariate regression analysis identified 4 independent graft-loss predictors: low eGFR at 1 year (hazard ratio, 12.49), interstitial fibrosis and tubular atrophy (hazard ratio, 2.22), glomerular and peritubular inflammation and transplant glomerulopathy (hazard ratio, 2.26), and the presence of complement-binding donor-specific anti-HLA antibodies (hazard ratio, 4.78).
Finally, including complement-binding donor-specific anti-HLA antibodies in the reference model improved risk stratification, as shown by a continuous net reclassification improvement of 0.75 (95% CI, 0.54 to 0.97).
By Xiaozhou Liu and Adrienne Cheung
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