A Critical Appraisal of Methods to Grade Transplant Glomerulitis in Renal Allograft Biopsies

Abstract

Transplant glomerulitis is an increasingly recognized lesion in renal transplant biopsies. To develop a refined grading system, we defined glomerulitis by the presence of ≥5 leukocytes/glomerulus and evaluated 111 biopsies using three different grading systems: (i) percentage of glomerular involvement, (ii) peak inflammation in the most severely affected glomerulus and (iii) presence/absence of endocapillary occlusion by inflammatory cells. Endocapillary occlusion had no impact on graft survival, but was associated with increased serum creatinine, proteinuria and subsequent transplant glomerulopathy. Grading based on either percent or peak glomerular involvement correlated with graft failure and peritubular capillaritis. However, the percent glomerular involvement method had the additional advantage of displaying associations with: concurrent proteinuria, focal or diffuse immunoperoxidase peritubular capillary C4d staining, 1-year postbiopsy serum creatinine, subsequent detection of donor-specific antibody and development of transplant glomerulopathy. Patients with >75% glomerular involvement also revealed persistent high-grade glomerulitis on follow-up biopsies despite antirejection treatment. In conclusion, grading of glomerulitis is a meaningful exercise, and a quantification system based on percentage of glomerular involvement shows the most robust associations with clinical parameters and prognosis.

The Clinical and Genomic Significance of Donor-Specific Antibody–Positive/C4d-Negative and Donor-Specific Antibody–Negative/C4d-Negative Transplant Glomerulopathy

“…Batal et al reported that glomerulitis is associated with higher ptc scores, C4d positivity, and subsequent development of DSA and TGP, but not with interstitial inflammation, tubulitis, intimal arteritis, or T cell-mediated acute rejection (27). The same group later documented higher intraglomerular and peritubular capillary granzyme B+ leukocytes in 25 biopsy specimens with glomerulitis (28).…”

Banff 2013 Meeting Report: Inclusion of C4d-Negative Antibody-Mediated Rejection and Antibody-Associated Arterial Lesions

“…Addition of CD68 staining did not improve inter-observer agreement when glomerulitis was scored using the definition that includes endothelial enlargement/capillary occlusion. Whether such agreement would be improved by addition of a threshold number of leukocytes/glomerulus to the current definition, as suggested by Batal et al (6), is an issue for future consideration.…”

Acute and chronic antibody-mediated rejection in pediatric kidney transplantation

“…However, the new consensus guidelines should be used in routine assessment. The excellent work of Randhawa's group [9] for the definition of transplant glomerulitis can still be recommended. Another new and debatable addition to the criteria for acute antibody-mediated rejection is mRNA transcriptome expression analysis [5].…”