Histologic Case Definition of an Atypical Glomerular Immune-Complex Deposition Following Kidney Transplantation

Kuo-Kai Chin; Vivek Charu; Michelle M O'Shaughnessy; Megan L Troxell; Xingxing S Cheng

doi:10.1016/j.ekir.2020.01.022

Histologic Case Definition of an Atypical Glomerular Immune-Complex Deposition Following Kidney Transplantation

Kidney Int Rep. 2020 Feb 5;5(5):632-642. doi: 10.1016/j.ekir.2020.01.022. eCollection 2020 May.

Authors

Kuo-Kai Chin^{1

2}, Vivek Charu³, Michelle M O'Shaughnessy^{4

5}, Megan L Troxell³, Xingxing S Cheng⁴

Affiliations

¹ Stanford University School of Medicine, Stanford University, Stanford, California, USA.
² Department of Medicine, Brigham and Women's Hospital, Brookline, Massachusetts, USA.
³ Department of Pathology, Stanford University Medical Center, Stanford, California, USA.
⁴ Department of Medicine, Division of Nephrology, Stanford University Medical Center, Stanford, California, USA.
⁵ Department of Nephrology, Cork University Hospital, Cork, Ireland.

Abstract

Introduction: Immune-complex deposition in the transplanted kidney can present as well-phenotyped recurrent or de novo glomerular disease. However, a subset, herein termed immune-complex glomerulopathy not otherwise specified (ICG-NOS), defies classification. We quantified, categorized, and characterized cases of transplant ICG-NOS occurring at a single US academic medical center.

Methods: We retrospectively reviewed our single-institution pathology database (July 2007-July 2018) to identify and categorize all cases of immune-complex deposition in kidney allografts (based on immunofluorescence microscopy). We extracted clinicopathologic and outcome data for ICG-NOS (i.e., immune complex deposition not conforming to any well-characterized glomerular disease entity).

Results: Of 104 patients with significant immune deposits, 28 (27%) were classified as ICG-NOS. We created 5 mutually exclusive ICG-NOS categories: Full-house, Quasi-full-house, IgA-rich, C1q-rich, and C1q-poor. Overall, 16 (57%) patients met criteria for definite or possible allograft rejection, including 9 (32%) with antibody-mediated rejection (ABMR), 3 (11%) suspicious for ABMR, 1 (4%) with T-cell-mediated rejection (TCMR), and 9 (32%) with borderline TCMR. After a median follow-up of 2.3 (range, 0.1-14.0) years after biopsy, 7 (25%) allografts had failed and an additional 8 (29%) had persistent renal dysfunction (hematuria, 14%; proteinuria, 21%; and estimated glomerular filtration rate <60 ml/min per 1.73 m², 11%).

Conclusion: In contrast to prior studies, our findings suggest that ICG-NOS is not necessarily a benign glomerular process and that there may be an association between ICG-NOS and alloimmunity. Our immunofluorescence-based classification provides a framework for future studies aiming to further elucidate ICG-NOS pathogenesis and prognosis.

Keywords: classification; glomerulonephritis; immune complex; pathology; transplant.