An integrative approach for the assessment of peritubular capillaritis extent and score in low-grade microvascular inflammation—associations with transplant glomerulopathy and graft loss. Issue 1 (20th July 2018)

• Record Type: Journal Article
• Authors: Kozakowski, Nicolas; Herkner, Harald; Eskandary, Farsad; Eder, Michael; Winnicki, Wolfgang; Kläger, Johannes; Bond, Gregor; Kikić, Željko
• Is Part Of: Nephrology dialysis transplantation. Volume 34:Issue 1(2019)
• Page Start: 166
• Page End: 174
• Publication Date: 2018-07-20
• Subjects: graft loss -- microvascular inflammation -- peritubular capillaritis -- ptc extent -- transplant glomerulopathy; Nephrology -- Periodicals; Hemodialysis -- Periodicals; Kidneys -- Transplantation -- Periodicals; Hemodialysis; Kidneys -- Transplantation; Nephrology; Periodicals; 616.61
• DOI: 10.1093/ndt/gfy192
• Languages: English
• ISSNs: 0931-0509

Abstract

ABSTRACT: Background: Peritubular capillaritis (ptc), reported by the ptc score, is a major feature of kidney allograft rejection and microvascular inflammation (MVI). MVI sum scores (ptc + glomerulitis score ≥2) are accepted diagnostic surrogates of human leucocyte antigen (HLA)–antibody interaction. However, low-grade inflammation is common and ptc scores (number of leucocytes/capillary) may not mirror all aspects of ptc morphology. Recently we observed a relationship of the diffuse extent of ptc (inflammation of >50% of the renal cortex) with graft loss and significantly higher donor-specific antibody levels, suggesting potential inclusion of diffuse ptc as an additional surrogate of antibody–antigen interaction. Methods: We sought to assess how a combination of ptc score and extent in low-grade inflammation (ptc1) affects transplant glomerulopathy (TG) and graft loss risk. Patients ( n = 616) were assessed for MVI in first indication biopsies. Cases with a ptc score of 1 but diffuse extent (ptc1diffuse, g-score = 0, n = 26) were considered additional surrogates of HLA–antibody interaction and compared with MVI ≥2 and MVI <2. Results: The ptc1diffuse and MVI score ≥2 subjects had worse graft survival (42% and 59%) compared with an MVI score <2 (70%) (P = 0.002). The incorporation of ptc1diffuse in the MVI score ≥2 increased the receiver operating characteristics curve for TG [area under the curve (AUC) 0.602; P = 0.008] compared with a Banff MVI score ≥2 (AUC 0.56; P = 0.12); cases with baseline TG were excluded. In multivariate analysis, ptc1diffuse remained independently related to TG (odds ratio 3.89; P = 0.008) and graft loss (hazard ratio 2.64; P = 0.001) even after inclusion of all rejection episodes. Conclusion: An integrated view of ptc morphology including diffuse ptc in MVI is superior for TG and graft loss risk assessment.