Determinants of Long-Term Graft Outcome in Transplant Glomerulopathy

Abstract

Transplant glomerulopathy (TG) is a renal allograft disease defined by glomerular basement membrane duplication with peritubular capillary basement membrane multilayering (PTCML), and associated with anti-human leukocyte antigen antibodies and C4d. Outcome in TG is poor but variable, and prognostic factors, particularly those affecting long-term outcome, are not well known. We investigated several potentially prognostic clinical and pathologic factors in TG and evaluated estimated glomerular filtration rate (eGFR) slopes to assess graft function and early decline. We examined all cases of TG from 2001 to 2005 with at least 4-year follow-up after biopsy, excluding those with a second confounding diagnosis. Among 36 cases of pure TG, mean graft age at biopsy was 8.8±6 years. C4d stain was positive in 11 (33%) cases. Clinical characteristics at biopsy were not different based on C4d. C4d was associated with greater PTCML (P=0.03), peritubular capillaritis (P=0.04), and glomerulitis (P=0.03). Death-censored graft survival was significantly associated with interstitial fibrosis (P=0.001), PTCML (P=0.001), and arteriolar hyalinosis (P=0.007), and it showed a trend with proteinuria (P=0.07) and C4d positivity (P=0.08). C4d-positive cases also showed a trend toward rapid graft loss. Analysis of eGFR slopes showed a pattern of preserved, slightly negative slope from transplant until approximately 1 year before biopsy, at which point the slope became significantly more negative (P<0.001). Interstitial fibrosis, PTCML, and arteriolar hyalinosis were significant predictors of graft survival in TG. C4d positivity was associated with a more rapid rate of function decline. eGFR slope data showed significant deterioration in graft function well before the diagnostic biopsy.