Long Term Kidney Graft Injury in Highly Sensitized Recipients
Naima Carter-Monroe, Edward D Kraus, Andrea A Zachary, Lorraine C Racusen, Lois J Arend, Robert A Montgomery, Serena M Bagnasco. Johns Hopkins University School of Medicine, Baltimore, MD
Background: The evolution of pathologic changes over time in highly sensitized renal graft recipients has not been well characterized.
Design: 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.
Results: Protocol and “for cause” biopsies were available in 120 pts: 38 M, 82 F; 98 whites, 16 blacks, 6 of other race; median age 45 years; median FU 3.2 years. Median PRA was 95. DSA at transplant were present in 81 pts: 31 class I only, 27 class II only, 23 both. Five pts died (4 with functioning graft), 14 lost their graft. Biopsy proven rejections were detected in 83 pts: antibody mediated rejection (AMR) in 19%, cell mediated rejection (CMR) in 31%, both in 18%, none in 38 pts, 9 pts had BK nephropathy. Rejections were most frequent in the first month (20% CMR, 16% AMR). 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. After the first year, 56 pts required graft biopsies, revealing CMR in 9 pts, AMR in 11 pts, both CMR and AMR in 3 pts, mixed CMR and AMR in 2 pts, glomerulitis (g≥1) and capillaritis (ptc≥1) but negative C4d in 8 pts, borderline inflammation in 5 pts. There was progressively higher average tubulointerstitial scarring (ci+ct) from 3 to 6 to 12 months (P<0.001), and from 1 to 2 to 3 years (P<0.05) post transplant. Transplant glomerulopathy (cg ≥1) developed in 54 pts, 14 by 6 months, and 23 by year 1, with proteinuria in 31, and was preceded by capillaritis (g≥1, ptc≥1) with positive C4d in 38%, and with negative C4d in 29%. Capillaritis (g≥1 and ptc≥1) with negative C4d was detected in the biopsies of 25 pts, of which at least 8 had moderate to high strength DSA, potentially indicating episodes of C4d-negative AMR.
Conclusions: Our observations support a role for capillaritis, even with negative C4d, in the development of transplant glomerulopathy. Despite good graft survival, acute and chronic allograft injury due to both AMR and CMR develop over time in incompatible allografts.
Category: Kidney (does not include tumors)
Tuesday, March 5, 2013 11:30 AM
Proffered Papers: Section H, Tuesday Morning