Abstract
Background: Peritubular capillaritis (ptc), an engorgement of immune cells in the peritubular capillaries, is one of the diagnostic criteria of antibody-mediated rejection (AMR). According to the Banff classification the severity of ptc, its distribution and its cellular composition should be routinely reported. It remains unclear whether or to which extent the morphological presentation of ptc is associated with clinical outcomes. Methods: This retrospective study included 749 biopsied renal transplant recipients (transplantation 1999 - 2006; 1322 indication biopsies). Detailed characterization of ptc included (i) its composition [mainly monocytic (>75% monocytes), granulocytic (>75% granulocytes) or mixed], (ii) its distribution [focal (10-50% of renal cortex peritubular capillaries) vs. diffuse (>50 %)] and (iii) its severity scored according to the Banff scheme (ptc: 1,2,3), respectively. Biopsy results were analyzed in relation to clinical outcomes. Results: Ptc was present in 24.9% (n=329) of the studied allograft biopsies. Ptc scores 1, 2 and 3 were observed in 43%, 47% and 10% of these specimens. Leucocyte subpopulations were categorized focal vs. diffuse monocytic (11%/24%), focal vs. diffuse granulocytic (4%/4%), or focal vs. diffuse mixed (14%/20%). In 23% of the cases ptc was not classified (e.g. vicinity of tubular necrosis, pyelonephritis or infarct). Ptc scores (1, 2 or 3) were associated with both diagnosis of AMR and cellular rejection (ACR). Diffuse monocytic or mixed ptc (OR=4.51, 95% CI 1.82-11.16, and OR=6.8, 2.44-19.36, p≤0.001), but not granulocytic ptc (OR=3.81, 95% CI 0.41-35.02, p=0.2) were associated with AMR. At the same time, diffuse ptc was associated with ACR, regardless of its composition (monocytic: OR=6.1, 95%CI 3.61-12.44; granulocytic: OR=6.69, 1.58-28.41; mixed: OR=8.05, 4.06-15.96; p≤0.01). In uni- and multivariate analysis ptc 3 (OR=2.56, 95%CI 1.24-1.96, p=0.011), diffuse monocytic or mixed ptc (OR=1.75, 95%CI 1.01-3.06, p=0.048 and OR=1.75, 1.03-3.26, p=0.04) were risk factors for inferior graft survival. Conclusions: Our results underscore a high relevance of the detailed qualitative and quantitative characterization of peritubular capillaritis in indication biopsies as a predictor for inferior clinical outcomes.
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