Histopathologic Correlates of Progression of Transplant Glomerulopathy (TG).

Abstract

Introduction TG has a poor prognosis and treatments have not been established. Pathological correlates of TG progression are not well defined and may help identify those at risk for progression. Methods We included all patients diagnosed with TG who also had a subsequent indication biopsy. The biopsies were reviewed by the pathologist and assigned microvascular injury scores (g+ptc), and chronic tubulointerstitial injury scores (ci+ct). Chronic glomerulopathy scores (cg) were also assigned. Change in the (g+ptc), (ci+ct), and cg scores were measured. A serum creatinine (Cr) increase of < 20% was considered stable. Changes in pathological scoring were compared in patients with and without a stable creatinine. Treatment with rituximab and changes in donor specific Ab (DSA) were also evaluated. Results Thirteen patients were evaluated. Average follow-up was 731 days from the index biopsy. The mean Δ(g+ptc) was -1.5, Δ(ci+ct) 1.7, and Δcg 0.8. There was a similar decrease in the g+ptc score in those with a stable Cr vs. unstable Cr (-1.6 vs. -1.5). Those was a stable Cr had less chronic change [Δ(ci+ct) 1.2 vs. 2.0) and less chronic glomerular changes (Δcg 0.4 vs. 1). Patients treated with rituximab had a better Δ(g+ptc) and Δ(ci+ct) scores but no differences in cg [Δ(g+ptc) -2.5 vs. -0.7, Δ(ci+ct) 0.83 vs. 2.4, Δcg 0.86 vs. 0.86). Rituximab treated patients also had an improvement in the DSA relative intensity score, a measure that takes into account the number and strength of DSAs. Finally, those with a stable Cr who also received rituximab did the best in regards to changes in ci+ct scores while those who did not receive rituximab tended toward worse scores (table 1) Conclusion Changes in (g+ptc) scores in patients with TG did not seem to correlate with clinical stability, but changes in (ci+ct) scores did. Rituximab seemed to improve microvascular inflammation while slowing down progression of chronic tubulointerstitial injury. It is possible that the effect of rituximab on DSA plays a role in slowing down the development of chronic tubulointerstitial changes.Table: No Caption available.