Interstitial fibrosis represents a major cause of kidney allograft failure. Addressing the causes of accelerated ageing of kidney allografts represents an important challenge to improve long-term transplant outcomes. We investigated the role of donor-specific anti-HLA antibodies (DSA) in the progression of kidney allograft interstitial fibrosis.

We prospectively enrolled 913 kidney recipients transplanted between 2004 and 2010 in two centers in Paris. All patients were assessed for allograft interstitial fibrosis on biopsies performed at Day 0 and at 1 year after transplantation using the IF/TA Banff grade. We also integrated all the “for cause” biopsies performed in the first year post transplant (N=1035) and after the first year (N=784, median time of biopsies 18.4 months; IQR, 13.3-40.4). All patients were systematically screened for DSA by Luminex SAB at the time of transplantation (Day 0) and within the first year post-transplantation. The progression of IF/TA within the first year post-transplantation was evaluated by the difference between the 1-year and Day-0 IF/TA grades ([Delta]IF/TA). The progression of IF/TA over the long term was modelled using mixed-effect regression model.

The distribution of IF/TA on pre-implantatory biopsies (N=913) was as follows: 726 (80%) patients had IF/TA0, 145 (15%) IF/TA1, 36 (4%) IF/TA2 and 6 (1%) IF/TA3 as compared to 325 (35%), 263 (29%), 173 (19%), and 152 (17%) on 1-year biopsies (N=913), respectively (P<0.001). Over the first year, 507 (56%) patients presented progression of IF/TA ([Delta]IF/TA>0). Patients with Day-0 DSA (N=198) showed increased progression of fibrosis within the first year ([Delta]IF/TA of 1.08±1.15) as compared to patients without Day-0 DSA (N=715, 0.86±1.12) (P=0.016).

Patients with post-transplant DSA (preformed or de novo) (N=236) exhibited accelerated progression of IF/TA as compared to patients without post-transplant DSA (N=677) (P for interaction between DSA and time=0.0078) when integrating the biopsies performed at 1-year post transplant and beyond.

Pre-transplant circulating anti-HLA DSA increase premature allograft fibrosis and post-transplant DSA accelerate the progression of allograft fibrosis over the long term.

CITATION INFORMATION: Gosset C, Viglietti D, Rabant M, Pillebout E, Bouquegneau A, Taupin J, Glotz D, Legendre C, Duong Van-Huyen J, Loupy A, Lefaucheur C. Circulating Donor-Specific Anti-HLA Antibodies Accelerate the Progression of Interstitial Fibrosis in Kidney Allografts. Am J Transplant. 2017;17 (suppl 3).

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