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

Transplant glomerulitis is an increasingly recognized lesion in renal transplant biopsies. To develop a re-fined 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 in-flammation 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 in-creased 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 immunoperox-idase peritubular capillary C4d staining, 1-year post-biopsy serum creatinine, subsequent detection of donor-specific antibody and development of trans-plant glomerulopathy. Patients with >75% glomeru-lar involvement also revealed persistent high-grade glomerulitis on follow-up biopsies despite antirejec-tion 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