Transcript Kidney allografts with biopsy features of chronic mixed rejection
Kidney allografts with biopsy features of chronic mixed rejection reflect poorer survival than those with pure chronic antibody-mediated rejection D. Dobi, Zs . Bodó, É. Kemény, K. Boda a , P. Szenohradszky b , E. Szederkényi b , B. Iványi Departments of Pathology, Medical Physics and Informatics a and Surgery b University of Szeged, Szeged, Hungary
Introduction
In late dysfunctional kidney allograft biopsies three rejection phenotypes can be observed: • chronic antibody-mediated rejection (AMR) • acute T-cell-mediated rejection (TMR) • chronic active TMR
Chronic AMR: transplant glomerulopathy and/or transplant capillaropathy cg ptcml
Acute TMR: interstitial infiltrates and tubulitis (interstitial rejection, ISR) with or without intimal arteritis
Chronic active TMR: mononuclears in intimal fibrosis (cv mo )
• Frequency: chronic AMR > acute TMR; chronic active TMR is exceptional • Chronic AMR and TMR may concur, termed chronic mixed rejection (CMR)
Objectives
To analyze • the histological patterns of chronic mixed rejection (CMR) • the clinicopathological relevance of the different patterns of CMR
Material and methods
• From 2001 to 2011, 61 biopsies displayed the histological features of chronic AMR (cg and/or ptcml ± C4d-positivity) • Luminex data were not avaible • Re-evaluation according to the Banff scheme (v, g, i, t, ptc, cg, ci,ct, ah) plus • Scoring of chronic arterial changes: mononuclears in intimal fibrosis (cv mo ), intimal fibrosis (cv IF ), intimal fibroelastosis (cv IFE ); and tubular HLA-DR and ptcml
• Staining of chronic active arteritis (cv mo ) cases with CD3 and CD68 in adjacent sections • Two groups for clinicopathological analysis: purely CAMR
vs
CMR • Statistics: Spearman’s correlation, hierarchical cluster analysis, Kaplan-Meier estimator, Cox regression
Results: main clinical data
All patients (n=61) Purely CAMR (n=35) Posttransplant time (months) eGFR (ml/min/1.73 m 2 ) Postbiopsy follow-up (months) 66 ±49 26 ±12 23 ±22 70 28 26 ±49 ±12 ±22 CMR (n=26) 60 23 19 ±49 ±13 ±20
p
ns ns ns
35
Histological patterns
12 4 Purely CAMR Chronic active TMR Chronic active TMR and acute ISR CMR 10 Acute ISR
Features of chronic active arteritis Severe luminal narrowing (median score 3), mononuclears scattered throughout the fibrotic intima, T-cell predominance PAS CD3 CD68
Significant (p<0.05) and positive Spearman correlation coefficients between Banff scores and chronic arterial changes t i 0.769
HLA-DR 0.606
t 0.654
HLA-DR cv mo ptc 0.347
C4d g 0.2750.354
0.363
cv mo cg ptcml cv IF ci ct 0.301 0.264
ah ptc 0.3280.331
C4d 0.303
g 0.338
cg 0.258
ptcml 0.414 0.269 0.263
cv IF ci 0.806 0.299
ct ah cv IFE cv IFE
cv IF cv mo cv IFE Hierarchical cluster analysis
Mean eGFR values in purely CAMR and CMR 25 20 15 50 45 40 35 30 Time before (-) and after (+) biopsy (Bx) (months) purely CAMR CMR
Therapy Steroid pulse Postbiopsy therapy Purely CAMR CMR CAMR (n=35) Chronic active TMR (n=12) Chronic active TMR and acute ISR (n=4) 5 5 4 Acute ISR (n=10) 10 Intensification of maintenance immunosuppression Anti-thymocyte globulin Plasmapheresis Left untreated 8 0 0 22 6 0 0 2 1 2 2 0 0 0 0 0
Mean graft survival in purely CAMR and CMR groups 50
vs
22 months Purely CAMR CMR p=0.011
Multivariable Cox regression of morphological variables HLA-DR g C4d CNI-tox.
cv
mo
cv
IF
ct ptc cg ci t i ptcml cv
IFE
ah
Discussion
I. CMR was frequent in our series (43%) II. Chronic active arteritis appeared to be T cell-related a. T-cell predominance in 14/16 cases b. Clustered with TMR lesions C. Lefaucheur et al. Antibody-mediated vascular rejection of kidney allografts: a population-based study. Lancet 2013; 381: 313-319.
III. CMR was characterized by poorer allograft survival and more reduced allograft function than purely chronic AMR if chronic active arteritis was part of the TMR component IV. The immunohistochemical profiling of chronic active arteritis is recommended