Kidney Transplant With Low Levels of DSA or Low Positive B-Flow Crossmatch: An Underappreciated Option for Highly Sensitized Transplant Candidates

Abstract

Background: Avoiding donor-specific antibody (DSA) is difficult for sensitized patients. Improved understanding of the risk of low level DSA is needed.

Methods: We retrospectively compared the outcomes of 954 patients transplanted with varied levels of baseline DSA detected by single antigen beads and B flow cytometric crossmatch (XM). Patients were grouped as follows: -DSA/-XM, +DSA/-XM, +DSA/low +XM, +DSA/high +XM, and -DSA/+XM and followed up for a mean of 4.1 ± 1.9 years (similar among groups, P = 0.49).

Results: Death-censored allograft survival was similar in all groups except the +DSA/high +XM group, which was lower at 79.1% versus 96.2% in the -DSA/-XM group (P < 0.01). The incidence of chronic antibody-mediated rejection (CAMR) based on surveillance biopsy was higher with increasing DSA (8.2% -DSA/-XM, 17.0% +DSA/-XM, 30.6% +DSA/low +XM, and 51.2% +DSA/high +XM, P < 0.01), but similar in groups without baseline DSA (8.1% -DSA/-XM vs 15.4% -DSA/+XM, P = 0.19). Having a calculated panel-reactive antibody (cPRA) of 80% or greater was independently associated with CAMR (hazard ratio, 5.2; P = 0.03) even when DSA was undetected at baseline. By 2 years posttransplant, the incidence of CAMR was 19.4% in patients with cPRA of 80% or greater and undetected DSA and negative XM at baseline.

Conclusions: Kidney transplantation with low-level DSA with or without a low positive XM is a reasonable option for highly sensitized patients and may be advantageous compared with waiting for a negative XM deceased donor. The risk for CAMR is low in patients with no DSA even if the XM is positive. Patients with cPRA of 80% or greater are at risk for CAMR even if no DSA is detected.

Figure 1. Donor Specific Antibody Characteristics

The characteristics of donor specific antibody present at baseline among the following transplant groups: +DSA/-XM (-XM), +DSA/low+XM (low+XM), and +DSA/high+XM (high+XM).

Figure 2. Patient and Allograft Survival stratified by DSA and B-flow Crossmatch at Baseline

The mean follow-up was similar among groups and was 4.1±1.9 years, p=0.82. Patient and overall allograft survival were similar among groups, p=0.82 and p=0.06 respectively. Lower death-censored allograft survival was observed in the +DSA/high+XM group, p<0.01. Death-censored allograft survival was similar in other groups,

Figure 3. Patient and Allograft Survival stratified by DSA Class at Baseline

Patients with both class I + class II DSA at baseline had inferior overall and death-censored allograft (p<0.01).

Figure 4. Microvascular Inflammation and Chronic AMR detected on Surveillance Biopsy

The prevalence of peritubular capillaritis, glomerulitis, and chronic AMR was higher in groups with higher DSA at all time points studied (p<0.01 *Cochran test for trend −DSA/-XM and +DSA groups). The prevalence of peritubular capillaritis, glomerulitis, and chronic AMR was similar in patients with undetected DSA and negative or positive XM. († -DSA/-XM and −DSA/+XM groups p=0.37,p=0.09, and p=0.38 respectively). ** No patients in the −DSA/+XM group had peritubular capillaritis at 5 years.

Figure 5. Allograft Function and Proteinuria

Patients in the +DSA/high+XM group had lower GFR at 1,2 and 5 years posttransplant than the −DSA/-XM group as measured by iothalamate clearance, p<0.01. GFR was between the −DSA/-XM and +DSA/-XM, +DSA/low+XM, and −DSA/+XM groups at 1,2 and 5 years. Proteinuria was also higher in the +DSA/high+XM group as compared to the −DSA/-XM group at 1 year posttransplant, p<0.01.

Figure 6. Incidence of Chronic AMR

The overall incidence of chronic AMR was 11.7% and was determined by examining both surveillance and indication biopsies. The incidence correlated with increasing DSA at baseline and was the following: 8.2% -DSA/-XM, 17.0% +DSA/-XM, 30.6%+DSA/low + XM, and 51.2% in the +DSA/high+XM group, p<0.01 (Cochran Test for Trend). The incidence of chronic AMR was similar in the −DSA/-XM and −DSA/+XM groups (8.2% vs. 15.4%, p=0.19).