We studied the development of kidney graft injury over 1-9 years post-transplant follow up (FU) in 218 patients transplanted with an HLA-incompatible kidney between 2000 and 2010.
Protocol and for cause biopsies were available in 129 pts: 41 M, 88 F; 105 whites, 17 blacks, 7 of other race; median age 41 years; median FU 3.2 years. Median PRA was 93. DSA at transplant were present in 96 pts: 33 class I only, 26 class II only, 38 both. Five pts died (4 with functioning graft), 15 lost their graft. Graft survival at 5 years was 78%. The average eGFR (ml/min/1.73 m2) declined significantly (P<0.001) from 63 at 3 months to 54 at 1 year, and was 48 at 4 year.
Biopsy proven rejections were detected in 71% pts throughout FUs: cell mediated rejection (CMR) in 43%, antibody mediated rejection (AMR) in 20%, both in 18%, no pathologic changes in 11% pts, 7% pts had BK nephropathy. Rejections were most frequent in the first month (21% CMR, 15% AMR).
After the first year, 62 pts required graft biopsies, revealing CMR in 20 pts, AMR in 12 pts, both CMR and AMR in 3 pts, borderline inflammation in 14 pts. There was progressively higher average tubulointerstitial scarring (ci+ct) from 3 to 6 to 12 months (P<0.001), and in the subsequent 3 years post transplant (P<0.05). Overall 43% pts developed transplant glomerulopathy (TxGN, cg ≥1), as early as 3 months in 6 pts, and in 32% pts by 12 months, with proteinuria in 58%. TxGN was preceded by capillaritis (g≥1, ptc≥1) in 80% pts, with positive C4d in 62%, and with negative C4d in 38%. Of all pts with capillaritis (g≥1 and ptc≥1) with negative C4d at least 8 had moderate to high strength DSA, potentially indicating episodes of C4d-negative AMR.
Conclusions: Despite good graft survival, acute and chronic allograft injury due to both AMR and CMR develop over time in incompatible allografts. CMR occurred more frequently than AMR throughout FU. Our observations support a role for capillaritis, even with negative C4d, in the development of transplant glomerulopathy.
To cite this abstract in AMA style:Bagnasco S, Zachary A, Racusen L, Arend L, Montgomery R, Kraus E. Progression of Pathologic Changes in Kidney Allografts of HLA-Incompatible Transplant Recipients [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/progression-of-pathologic-changes-in-kidney-allografts-of-hla-incompatible-transplant-recipients/. Accessed October 28, 2020.
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