Chronic Transplant Glomerulopathy

Abstract

Chronic transplant glomerulopathy (CTG), investigated in a large single-center study by Akalin et al. (1), is an interesting pathologic lesion that develops in the renal allograft. It is characterized by endothelial cell injury or loss, accumulation of flocculent material in a widened subendothelial space, and mesangial interposition with deposition of new matrix along glomerular capillary walls. These progressive changes produce a thickened glomerular capillary profile and the capillary wall “double contours” that are demonstrable on periodic acid-Schiff and silver staining and that define CTG (2). Analogous changes occur in later stages of thrombotic microangiopathy (TMA) in the native kidney, initiated by endothelial injury and/or dysfunction. Development of this lesion in the renal allograft has been associated with worse graft outcome. CTG has been documented in the context of “chronic rejection” with antidonor antibody and may be strongly correlated with other features that are consistent with chronic/persistent/recurrent antibody-mediated rejection (AMR), including positive staining for C4d and multilayering of peritubular capillary basal lamina. Akalin et al. briefly reviewed this literature, including the seminal studies by Mauiyyedi et al. (3) and Regele et al. (4); however, studies of CTG correlation with C4d staining and detection of donor-specific antibody (dsAb) are emerging, and clearly many cases of CTG do not have these features at the time of biopsy. It is likely that the triad of CTG, C4d staining and presence of dsAb …