Interstitial fibrosis represents a major cause of kidney allograft failure. We investigated the independent contribution of circulating donor-specific anti-HLA antibodies (DSA) in the development of severe kidney allograft fibrosis with integration of traditional risk factors for allograft fibrosis.

We prospectively enrolled 1539 consecutive kidney recipients transplanted between 2004 and 2010 in two Paris centers, with systematic assessment of allograft fibrosis using the IF/TA Banff score on biopsies performed at 1-year post-transplantation. We considered all of the traditional determinants of allograft fibrosis reported in the literature, recorded at the time of transplantation and in the first year after transplantation. We also integrated DSA assessment and all the histologic diagnoses (“for cause” biopsies; N=1804) performed in the first year after transplantation.

We identified 498 (32%) patients with severe IF/TA (Banff grade≥2). DSA were associated with severe IF/TA at 1-year post transplant (adjusted OR, 1.53; 95%CI, 1.16-2.01; P=0.002), independently of the traditional determinants, including: T cell-mediated rejection, antibody-mediated rejection, BK virus-associated nephropathy, calcineurin inhibitor toxicity, initial disease recurrence, pyelonephritis, acute tubular necrosis, donor and recipient baseline parameters, and transplant characteristics. DSA remained associated with severe IF/TA even in patients without episode of antibody-mediated rejection (OR, 1.47; 95%CI, 1.10-1.96; P=0.008). Patients with DSA-associated severe IF/TA (N=154) showed increased microvascular inflammation (P<0.001), transplant glomerulopathy (P<0.001), C4d deposition in capillaries (P<0.001) and decreased allograft survival (P<0.001) as compared to patients with severe IF/TA without DSA.

Among the modifiable risk factors for severe IF/TA, DSA were found to be the first contributor, being involved in 11% of cases while T cell-mediated rejection, calcineurin inhibitor toxicity, acute tubular necrosis, pyelonephritis and BK virus-associated nephropathy were involved in 9%, 8%, 6%, 5%, and 4% of cases, respectively.

Circulating anti-HLA DSA are major contributor to severe allograft interstitial fibrosis independent of traditional risk factors and of antibody-mediated rejection.

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

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