Association of Ultrastructural Changes in Renal Allograft Biopsies With Diagnostic Elements of Antibody-mediated Rejection and Graft Outcomes.

Abstract

Background: The role of electron microscopy (EM) in the diagnosis of kidney allograft pathologies, particularly immunologic injury has not been well studied.

Methods: In this retrospective, single-center cohort study, we examined EM features in 796 biopsies from 623 patients at high risk for antibody-mediated rejection, with glomerular abnormalities in light microscopy, presence of donor-specific antibody (DSA), or any degree of albuminuria/proteinuria.

Results: Glomerular endothelial cell enlargement (GECE) > 50% was present in 29.1%, subendothelial expansion/basement membrane duplication in 24.5%, and peritubular basement membrane multilamellation > 4 (PTCML) in 18.5%. There was an incremental odds of worsening GECE from no DSA to class I DSA (odds ratio [OR], 2.75, P < 0.001; 95% confidence interval [CI], 1.7-4.5), class II DSA (OR, 3.44, P < 0.001, 95% CI, 2.5-4.7) and both classes (OR, 6.3, P < 0.001; 95% CI, 4.1-9.8). Moreover, the increase in number of antibodies was predictive of higher likelihood of worsening GECE (OR, 2.81, P < 0.001; 95% CI, 2.1-3.8 for 1 DSA; OR, 5.29, P < 0.001; 95% CI, 3.5-7.9 for 2-3; and OR, 8.45, P < 0.001; 95% CI, 4.7-15.3 for ≥4). Similar association was observed with PTCML. In multivariate analysis including DSA, subendothelial expansion/basement membrane duplication, and GECE >50%, but not PTCML were independently predictive of graft failure over mean follow-up of 63 mo (hazard ratio [HR], 1.6, P = 0.006, 95% CI, 1.2-2.3; HR, 2.0, P < 0.001; 95% CI, 1.4-2.9, respectively). Among a cohort with g, ptc, cg, and C4d scores 0, GECE >50% was independently associated with graft failure (HR, 2.58, P < 0.001, 95% CI, 1.6-4.3).

Conclusions: These observations support the wider use of EM in kidney transplant biopsies to help with earlier diagnosis of antibody-mediated rejection and to risk stratify the graft outcome.