Background: Transplant glomerulopathy (TG) has emerged as an important cause of kidney allograft loss. The prognosis of TG is overall poor but progression is variable and other factors affecting graft outcome, particularly concomitant pathologies on biopsies with TG, remain to be studied.

Methods: We identified all cases of TG diagnosed at our institution between 1 Jan 2001 and 31 Dec 2010 (follow-up to 31 Dec 2011), and comprehensively studied clinical and Banff histopathologic parameters. Time to graft failure (including total and death-censored), as a function of histopathologic indices, were graphically assessed using the Kaplan-Meier method. Both pathologic and clinical variables were explored in multivariable Cox regression models as predictors of time from TG diagnosis to the outcomes of interest. We also studied the value of a mean TG grade (average glomerular double contouring) as a predictor of graft outcomes.

Results: Among 129 first, for-cause, biopsies (2,980 person-months of follow-up), TG grade was mild in 29, moderate in 32, and severe in 68 cases. C4d was positive in 38%, significantly associated with peritubular and glomerular capillary inflammation, and slightly more common in earlier biopsies. Mean time from transplant to TG diagnosis was 9.1 (SD 6.4) years. Fifty-nine patients lost their grafts, 13 died with graft function, and 57 were alive with functioning grafts at the end of study. Kaplan-Meier curves showed death-censored graft survival to be significantly associated with interstitial fibrosis (P < 0.0001), arteriolar hyalinosis (P = 0.003), and TG grade (P = 0.03). In a multivariable Cox model, more than mild degrees of fibrosis, hyalinosis, and TG grade were associated with worse graft outcome. The mean TG grade correlated with, but did not add any additional predictive value, to the Banff TG grade. Capillaritis or the presence of C4d at the time of TG diagnosis did not associate with graft outcome.

Conclusions: Histopathologic factors must be considered when evaluating outcome in TG, especially if specific therapies for TG are to be correlated with graft survival. Arteriolar hyalinosis remains a major contributor to allograft failure. The mean TG grade parallels the Banff TG grade but does not appear to add prognostic value. Concomitant microcirculatory inflammation is common even in late biopsies but does not influence graft outcome at this stage.

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