Anti-HLA antibodies predict worse kidney-allograft survival

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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.

Click to read the study, published today in NEJM

Click to read an accompanying editorial in NEJM

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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