Rates and Determinants of Progression to Graft Failure in Kidney Allograft Recipients With De Novo Donor‐Specific Antibody. Issue 11 (10th June 2015)

• Record Type: Journal Article
• Authors: Wiebe, C.; Gibson, I. W.; Blydt‐Hansen, T. D.; Pochinco, D.; Birk, P. E.; Ho, J.; Karpinski, M.; Goldberg, A.; Storsley, L.; Rush, D. N.; Nickerson, P. W.
• Is Part Of: American journal of transplantation. Volume 15:Issue 11(2015:Nov.)
• Page Start: 2921
• Page End: 2930
• Publication Date: 2015-06-10
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.13347
• Languages: English
• ISSNs: 1600-6135

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ajt13347-sec-0001" sec-type="section"> <p>Understanding rates and determinants of clinical pathologic progression for recipients with <italic>de novo</italic> donor‐specific antibody (<italic>dn</italic>DSA), especially subclinical <italic>dn</italic>DSA, may identify surrogate endpoints and inform clinical trial design. A consecutive cohort of 508 renal transplant recipients (n = 64 with <italic>dn</italic>DSA) was studied. Recipients (n = 388) without <italic>dn</italic>DSA or dysfunction had an eGFR decline of −0.65 mL/min/1.73 m<sup>2</sup>/year. In recipients with <italic>dn</italic>DSA, the rate eGFR decline was significantly increased prior to <italic>dn</italic>DSA onset (−2.89 vs. −0.65 mL/min/1.73 m<sup>2</sup>/year, p < 0.0001) and accelerated post‐<italic>dn</italic>DSA (−3.63 vs. −2.89 mL/min/1.73 m<sup>2</sup>/year, p < 0.0001), suggesting that <italic>dn</italic>DSA is both a marker and contributor to ongoing alloimmunity. Time to 50% post‐<italic>dn</italic>DSA graft loss was longer in recipients with subclinical versus a clinical <italic>dn</italic>DSA phenotype (8.3 vs. 3.3 years, p < 0.0001). Analysis of 1091 allograft biopsies found that <italic>dn</italic>DSA and time independently predicted chronic glomerulopathy (cg), but not interstitial fibrosis and tubular atrophy (IFTA). Early T cell–mediated rejection, nonadherence, and time were multivariate predictors of IFTA. Independent risk factors for post‐<italic>dn</italic>DSA graft survival available prior to, or at the time of, <italic>dn</italic>DSA detection were delayed graft function, nonadherence, <italic>dn</italic>DSA mean fluorescence intensity sum score, tubulitis, and cg. Ultimately, <italic>dn</italic>DSA is part of a continuum of mixed alloimmune‐mediated injury, which requires solutions targeting T and B cells.</p> </sec> </abstract>