Abstract
BackgroundSince the term chronic allograft nephropathy (CAN) was removed from the Banff scheme in 2005, transplant glomerulopathy (TG) has been regarded as a clinicopathological entity that is one of the major causes of graft loss. To assess the distinction between CAN and TG, we performed a comprehensive evaluation comparing TG with traditional CAN.MethodsWe compared the clinicopathological features of 43 cases of TG with 43 matched cases of non-TG CAN (non-TG group) after renal transplantation. TG was diagnosed by light microscopy based on the double contours of the glomerular basement membranes, and the Banff 97 classification system was used to score TG severity (cg0-3).ResultsCompared to the control group, we found a significantly higher incidence of positivity for human leukocyte antigen class-I and II antibodies, a higher incidence of hepatitis C virus (HCV) infection, and poorer graft survival in TG patients. Clinically, TG was associated with a higher prevalence of proteinuria, hematuria, anaemia and hypoalbuminemia. Histologically, TG strongly correlated with antibody related microcirculatory injuries, including glomerulitis, peritubular capillaritis and peritubular capillary (PTC) C4d deposition. Interestingly, the TG patients showed a significantly higher incidence of IgA deposition than the control patients. C4d-positive TG was correlated with higher TG and PTC scores, and PTC C4d deposition was correlated with a more rapid progression to graft dysfunction. TG accompanied by HCV infection was associated with heavier proteinuria, higher TG and C4d scores, and poorer graft survival.ConclusionsTG presents clinicopathological features that are distinct from non-TG cases and leads to poorer outcomes. PTC C4d deposition is related to a more rapid progression to graft loss, suggesting ongoing antibody reactivity. HCV-positive TG is a more severe sub-entity, that requires further investigation.
Highlights
Since the term chronic allograft nephropathy (CAN) was removed from the Banff scheme in 2005, transplant glomerulopathy (TG) has been regarded as a clinicopathological entity that is one of the major causes of graft loss
peritubular capillary (PTC) C4d deposition is associated with a more rapid progression to allograft dysfunction, and we propose that this is due to ongoing antibody reactivity
We further propose that hepatitis C virus (HCV)-positive TG is a more severe sub-entity that requires further investigation
Summary
Since the term chronic allograft nephropathy (CAN) was removed from the Banff scheme in 2005, transplant glomerulopathy (TG) has been regarded as a clinicopathological entity that is one of the major causes of graft loss. Previous studies have demonstrated that TG is strongly associated with circulating alloantibodies [3,4], positive PTC C4d staining [5], and prior AMR [6] These findings substantiate the hypothesis that humoral immunity plays a key role in the pathogenesis of TG. A number of the observed lesions are considered to represent antibody-mediated injury, such as PTC C4d deposition, glomerulitis, peritubular capillaritis, PTC basement membrane multi-layering, and even TG. Lesions such as antibody-mediated microcirculation injuries were recently reported to be the major causes of late kidney transplant failure [9]. As TG is believed to be a result of antibody reactivity, it will be interesting to determine the relationship between TG and other antibody-mediated microcirculatory injuries
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