Poor Outcomes in Patients With Transplant Glomerulopathy Independent of Banff Categorization or Therapeutic Interventions

Abstract

Background: Transplant glomerulopathy (TG) may indicate different disease entities including chronic AMR (antibody-mediated rejection). However, AMR criteria have been frequently changed, and long-term outcomes of allografts with AMR and TG according to Banff 2017 have rarely been investigated.

Methods: 282 kidney allograft recipients with biopsy-proven TG were retrospectively investigated and diagnosed according to Banff'17 criteria: chronic AMR (cAMR, n = 72), chronic active AMR (cAAMR, n = 76) and isolated TG (iTG, n = 134). Of which 25/72 (34.7%) patients of cAMR group and 46/76 (60.5%) of cAAMR group were treated with antihumoral therapy (AHT).

Results: Up to 5 years after indication biopsy, no statistically significant differences were detected among iTG, cAMR and cAAMR groups in annual eGFR decline (-3.0 vs. -2.0 vs. -2.8 ml/min/1.73 m² per year), 5-year median eGFR (21.5 vs. 16.0 vs. 20.0 ml/min/1.73 m²), 5-year graft survival rates (34.1 vs. 40.6 vs. 31.8%) as well as urinary protein excretion during follow-up. In addition, cAMR and cAAMR patients treated with AHT had similar graft and patient survival rates in comparison with those free of AHT, and similar comparing with iTG group. The TG scores were not associated with 5-year postbiopsy graft failure; whereas the patients with higher scores of chronic allograft scarring (by mm-, ci- and ct-lesions) had significantly lower graft survival rates than those with mild scores. The logistic-regression analysis demonstrated that Banff mm-, ah-, t-, ci-, ct-lesions and the eGFR level at biopsy were associated with 5-year graft failure.

Conclusions: The occurrence of TG is closely associated with graft failure independent of disease categories and TG score, and the long-term clinical outcomes were not influenced by AHT. The Banff lesions indicating progressive scarring might be better suited to predict an unfavorable outcome.

Keywords: antihumoral therapy; chronic antibody-mediated rejection; graft survival; kidney transplantation; transplant glomerulopathy.

Figure 1

Flow chart of patients enrolled in this study. CCM, Charite Campus Mitte; CVK, Charite Virchow Klinikum. FSGS, focal segmental glomerulosclerosis; IgAN, IgA nephropathy; PGN, membranous proliferative glomerulonephritis; membranos GN, membranous glomerulopathy; iTG, solated transplant glomerulopathy; cAMR, chronic antibody-mediated rejection; cAAMR, chronic active antibody-mediated rejection.

Figure 2

(A) Effects of TG categories on the evolution of eGFR, for patient death or return to dialysis, no data of eGFR were imputed. (B) Effects of TG categories on the evolution of eGFR, for patient return to dialysis, eGFR were imputed as 5 ml/min/1.73 m^2. Individual eGFR course (thin dashed lines) and median eGFR (fat dashed lines) in relation to TG categories. Analyses are on the basis of serial eGFR measurements at 0, 6, 12, 18, 24, 36, 48, and 60 months. Box plots indicate the median, the interquartile range, the minimum, and the maximum of the measures.

Figure 3

The comparison of 5-year graft survival (left), death censored graft survival (middle) and 5-year patient survival (right) among iTG, cAMR and cAAMR groups. Bx, the studied biopsies.

Figure 4

The effect of AHT on the 5-year post Bx graft survival rates (left), DCGS rates (middle) and patient survival rates (right). AHT, antihumoral therapy; Bx, the studied biopsies.