Histologic Findings One Year After Positive Crossmatch or ABO Blood Group Incompatible Living Donor Kidney Transplantation

Abstract

Recent protocols have allowed successful positive crossmatch (+XM) and ABO incompatible (ABOI) kidney transplantation, although their long-term outcome is not clear. To begin to assess this issue we compared protocol biopsies performed 12 months posttransplant in 37 +XM, 24 ABOI and 198 conventional allografts. Although the majority in all three groups had only minimal histologic changes, transplant glomerulopathy (TG) was significantly increased in +XM (22% vs. 13% ABOI vs. 8% conventional, p = 0.015), and correlated with prior humoral rejection (HR) by multivariate analysis (odds ratio 17.5, p ≤ 0.0001). Patients with a prior history of HR also had a significant increase in interstitial fibrosis (No HR 54% vs. HR 86%, p = 0.045). In the absence of HR no difference in histologic changes was seen between groups, although all three groups had a demonstrable mild increase in interstitial fibrosis from biopsies performed at the time of transplant. Thus, although HR is associated with an increase in TG, in its absence allograft histology is similar in +XM, ABOI and conventional allografts 1 year posttransplant.

Donor-Specific Antibodies Accelerate Arteriosclerosis after Kidney Transplantation

“…Also evaluated were 38 late biopsies, performed primarily for clinical reasons. As will be seen, there was indeed an impressive acceleration of arteriosclerosis in DSAϩ patients, strongly associated with the presence of the newly described entity of subclinical AMR, 8,9 including microcirculation inflammation and C4d and DSA positivity.…”

Antibody-Mediated Renal Allograft Rejection

“…Among 28 patients with transplant glomerulopathy, 64% had circulating antibodies to donor class I (28%), II (39%), or both I and II (33%) HLA antigens (42). Patients with a positive pretransplantation cross-match have a higher incidence of transplant glomerulopathy at 1 yr in protocol biopsies (22 versus 8%) (43). Previous AHR is also a risk factor for transplant glomerulopathy (odds ratio 17.5); 44% of the recipients with AHR showed transplant glomerulopathy in a later biopsy (43).…”

“…Patients with a positive pretransplantation cross-match have a higher incidence of transplant glomerulopathy at 1 yr in protocol biopsies (22 versus 8%) (43). Previous AHR is also a risk factor for transplant glomerulopathy (odds ratio 17.5); 44% of the recipients with AHR showed transplant glomerulopathy in a later biopsy (43). Transplant glomerulopathy has a poor prognosis, even when subclinical, as detected in 1-yr protocol biopsies (graft survival approximately 50% 3 yr after diagnosis) (43).…”

“…Previous AHR is also a risk factor for transplant glomerulopathy (odds ratio 17.5); 44% of the recipients with AHR showed transplant glomerulopathy in a later biopsy (43). Transplant glomerulopathy has a poor prognosis, even when subclinical, as detected in 1-yr protocol biopsies (graft survival approximately 50% 3 yr after diagnosis) (43). In a series of 14 protocol biopsies that were taken 10 yr after transplantation, three had C4d deposition, and all three had circulating anti-HLA antibodies and transplant glomerulopathy (44).…”

“…The outcome will probably be determined primarily by the course and the pathogenicity of the alloantibody response itself. Even in ABO-incompatible grafts, accommodation may be incomplete: Transplant glomerulopathy is more frequent in 1-yr protocol biopsies of ABOincompatible grafts than in ABO-compatible recipients (13 versus 8%) (43). Controlled trials and further follow-up will be needed to interpret the long-term significance of "incidental" C4d deposition ( Figure 5).…”