Peritubular Capillary Pathology in Transplant Glomerulopathy
R John, A Tobar, A Konvalinka, K Alsaad, J Kim, H Reich, A Herzenberg. University Health Network and University of Toronto, Toronto, ON, Canada; University Health Network, Toronto, ON, Canada
Background: Transplant glomerulopathy (TG) is defined morphologically by glomerular basement membrane duplication in a renal allograft in the absence of immune deposits and evidence of thrombotic microangiopathy, and clinically by proteinuria and declining renal function. TG occurs in 10-20 % of grafts, shows association with alloantibodies (antibody mediated injury), cortical peritubular capillary C4d (PTCC4d) and basement membrane multilayering (PTCBMML), and when extensive, portends poor outcome. The etiology, pathogenesis, and features that affect prognosis remain unclear. Our aim was to examine pathological parameters that might further define TG and be useful in prognosis.
Design: Among 637 indication renal allograft biopsies between 2001 and 2005, TG was diagnosed in 58 (9%), 21 of whom had other secondary diagnoses, and were excluded. Histopathologic evaluation, immunohistochemistry for monocytes (CD68), PTC density (CD31), and angiogenesis (glomerular/tubulointerstitial VEGF and VEGFR), and outcome analysis (including creatinine clearance slopes) were performed on the 37 cases of pure TG.
Results: Mean patient age was 4817 years, and mean graft age was 8.86 years at biopsy. PTCC4d was positive in 11(30%), and associated with severe PTCBMML (p=0.02). TG was associated with decreased PTC density (using CD31). Fourteen (38%) patients lost their grafts, and 3(8%) died with a functional graft. Worse graft-survival was associated with moderate interstitial fibrosis (p = 0.04), >5 PTC monocytes (p = 0.02), and was associated with a non-significant trend with moderate PTCBMML. Glomerular monocytes and PTCC4d were not associated with outcome. Creatinine clearance slopes became significantly more negative approximately 1 year before biopsy.
Conclusions: PTCC4d is seen in a subset of TG and correlates with PTCBMML. Tubulointerstitial disease and damage to the PTC were predictors of graft survival. Reduced PTC density suggests a role for PTC injury in the progression of TG. Based on creatinine clearance slopes, proteinuria occurs at a late stage in the evolution of TG, so that earlier (protocol) biopsies may be necessary to diagnosis TG if disease intervention becomes possible.
Category: Kidney (does not include tumors)
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 186, Tuesday Afternoon