Acute Glomerulitis with Neutrophils May Underscore the Development of Glomerular Basement Membrane Multi-Lamination in Transplant Glomerulopathy.
Joseph P Gaut, Jeanne Shen, Michelle DeGuire, Christina Klein, Helen Liapis. Washington University School of Medicine, St. Louis, MO
Background: Acute glomerulitis (GL) in allograft biopsies is a distinct form of acute glomerular rejection, often seen in the early post-transplant period in association with antibody mediated rejection. A correlation with worse graft survival was previously reported. GL may also accompany transplant glomerulopathy (TGP) but its role in TGP pathogenesis remains unclear. The aim of this study was to evaluate the significance of GL in TGP.
Design: Renal transplant biopsies with TGP (n=50) and indication transplant biopsies without TGP (n=46, control) were retrospectively reviewed. GL was defined on light microscopy (LM) by the presence of monocytes or neutrophils affecting > 30% of glomeruli. TGP was defined by LM as mesangioproliferative glomerulonephritis and by EM with the following: endothelial fenestrae closure, subendothelial expansion, glomerular basement membrane (GBM) duplication, GBM multi-lamination, and luminal inflammatory cells. These EM features were scored as follows: 0 none; 1 <25% of capillary loops affected; 2 26-50% and 3 >50%. Laboratory data included urine protein. Statistical analysis using a t test was used to correlate GL, TGP and GBM multi-lamination with proteinuria.
Results: 10/50 (20%) cases of TGP showed GL compared with 1/46 (2%) control transplant biopsies. Neutrophils were a significant component of GL in 9/10 cases. EM was available for 43 cases (8 TGP with GL, 17 TGP, and 18 controls). The g score for TGP and TGP with GL was similar (1.8); 5/8 TGP cases with GL showed GBM multi-lamination. However, TGP with GL showed focal multi-lamination (score=1), whereas TGP without GL had a broad range of multi-lamination (score=0-3). There was a trend towards increased proteinuria associated with GL (3.35 g/day vs. 2.08 g/day). There was a stronger correlation of GBM multi-lamination with proteinuria (4.25 g/day vs. 2.35 g/day; p=0.08). 2/10 (20%) cases of TGP with GL showed peritubular capillary C4d staining compared with 12/25 (48%) cases of TGP without GL. The GBM multi-lamination score tended to correlate with C4d staining in PTC (1.2 versus 0.8).
Conclusions: Our results suggest a key role for neutrophils in the pathogenesis of GBM injury in TGP. We propose that neutrophils may mediate development of GBM multi-lamination in established TGP. A correlation of multi-lamination with C4d peritubular capillary immunoreactivity is consistent with the concept that both are features of chronic transplant capillaropathy.
Category: Kidney (does not include tumors)
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 267, Wednesday Afternoon