Isolated endarteritis and kidney transplant survival: a multicenter collaborative study

Abstract

Isolated endarteritis of kidney transplants is increasingly recognized. Notably, microarray studies revealed absence of immunologic signatures of rejection in most isolated endarteritis biopsy samples. We investigated if isolated endarteritis responds to rejection treatment and affects kidney transplant survival. We retrospectively enrolled recipients of kidney transplant who underwent biopsies between 1999 and 2011 at seven American and Canadian centers. Exclusion criteria were recipients were blood group-incompatible or crossmatch-positive or had C4d-positive biopsy samples. After biopsy confirmation, patients were divided into three groups: isolated endarteritis (n=103), positive controls (type I acute T cell-mediated rejection with endarteritis; n=101), and negative controls (no diagnostic rejection; n=103). Primary end points were improved kidney function after rejection treatment and transplant failure. Mean decrease in serum creatinine from biopsy to 1 month after rejection treatment was 132.6 µmol/L (95% confidence interval [95% CI], 78.7 to 186.5) in patients with isolated endarteritis, 96.4 µmol/L (95% CI, 48.6 to 143.2) in positive controls (P=0.32), and 18.6 µmol/L (95% CI, 1.8 to 35.4) in untreated negative controls (P<0.001). Functional improvement after rejection treatment occurred in 80% of patients with isolated endarteritis and 81% of positive controls (P=0.72). Over the median 3.2-year follow-up period, kidney transplant survival rates were 79% in patients with isolated endarteritis, 79% in positive controls, and 91% in negative controls (P=0.01). In multivariate analysis, isolated endarteritis was associated with an adjusted 3.51-fold (95% CI, 1.16 to 10.67; P=0.03) risk for transplant failure. These data indicate that isolated endarteritis is an independent risk factor for kidney transplant failure.

Keywords: acute allograft rejection; kidney; transplantation; vasculitis.

Figure 1.

Morphologic phenotypes in isolated endarteritis and control groups. (A) Micrograph showing isolated endarteritis involving an interlobular renal artery, which is an end artery and the only supply of oxygenated blood to a portion of kidney cortex. Arrows point subendothelial intimal mononuclear leukocyte infiltration (hematoxylin and eosin). Original magnification, ×400. (B) Comparison of pathology phenotypes associated with isolated endarteritis and control groups. Complement C4d deposition scores were not shown, because C4d-positive biopsies were excluded per study criteria.

Figure 2.

Functional response after rejection treatment in isolated endarteritis and positive controls. Kidney functional changes from biopsy to 1 and 6 months in patients who received rejection treatment (isolated endarteritis or type I acute T cell-mediated rejection with endarteritis) compared with untreated patients with normal histology in biopsies.

Figure 3.

Negative effect of isolated endarteritis on kidney transplant survival. (A and B) Kidney transplant survival curves at (A) 3 and (B) 8 years after biopsy-confirmed diagnosis (Kaplan–Meier analyses). (C) Forest plots of adjusted HRs of risk of transplant failure in patients with isolated endarteritis (red box) or type I acute T cell-mediated rejection (blue circle) with endarteritis according to separate clinical covariates compared with the reference control population (no rejection; Cox regression analyses).

Figure 4.

Effect of treatment on survival of kidneys with isolated endarteritis. Kidney transplant survival curves at 8 years after biopsy-confirmed diagnosis are shown (Kaplan–Meier analysis).

Figure 5.

Prognostic impact of isolated endarteritis in patients without evidence for ABMR. Survival of isolated endarteritis after exclusion of patients with ABMR histologic features according to the recently updated Banff 2013 criteria. Patients with glomerulitis (g)+peritubular capillaritis (ptc) sum score≥2 with g>1 or transplant glomerulopathy (cg) score>0 are classified as suspicious for ABMR, and patients with g+ptc=0 or 1 and cg=0 are classified as no evidence for ABMR. We excluded patients who met the aforementioned criteria for suspicious for ABMR from survival analysis. Kidney transplant survival curves at 8 years in patients without evidence for ABMR are shown (Kaplan–Meier analysis).

Figure 6.

Prognostic impact of isolated endarteritis in patients who were DSA-negative. Kidney transplant survival curves at 8 years in patients with no detectable DSA are shown (Kaplan–Meier analysis).