Donor-specific antibodies adversely affect kidney allograft outcomes

Abstract

The effect of low titers of donor-specific antibodies (DSAs) detected only by sensitive solid-phase assays (SPAs) on renal transplant outcomes is unclear. We report the results of a systematic review and meta-analysis of rejection rates and graft outcomes for renal transplant recipients with such preformed DSAs, defined by positive results on SPA but negative complement-dependent cytotoxicity and flow cytometry crossmatch results. Our search identified seven retrospective cohort studies comprising a total of 1119 patients, including 145 with isolated DSA-SPA. Together, these studies suggest that the presence of DSA-SPA, despite a negative flow cytometry crossmatch result, nearly doubles the risk for antibody-mediated rejection (relative risk [RR], 1.98; 95% confidence interval [CI], 1.36-2.89; P<0.001) and increases the risk for graft failure by 76% (RR, 1.76; 95% CI, 1.13-2.74; P=0.01). These results suggest that donor selection should consider the presence of antibodies in the recipient, identified by the SPA, even in the presence of a negative flow cytometry crossmatch result.

Figures

Figure 1.

Flow diagram of search results and identification of studies included in the analysis.

Figure 2.

Forest plots for risk stratified by flow crossmatch results for group 1. (A) Risk of AMR with and without DSA. (B) Risk of graft failure with and without DSA. For all forest plots, the solid line represents the null effect. The dotted line represents the summary effect for the studies included in the analysis. The shaded boxes are proportional to the relative weight of the studies used in each analysis. The center dot within the box represent the point estimate for that study and the horizontal line passing through each square represents the confidence interval of each study point estimate. The center of the diamond represents the summary effect and the lateral tips of the diamond represent the confidence intervals of the summary estimate.

Figure 3.

Forest plots for risk stratified by flow crossmatch results for groups 1 and 2. (A) Risk of AMR with and without DSA. (B) Risk of graft failure with and without DSA. For all forest plots, the solid line represents the null effect. The dotted line represents the summary effect for the studies included in the analysis. The shaded boxes are proportional to the relative weight of the studies used in each analysis. The center dot within the box represent the point estimate for that study and the horizontal line passing through each square represents the confidence interval of each study point estimate. The center of the diamond represents the summary effect and the lateral tips of the diamond represent the confidence intervals of the summary estimate.

Figure 4.

Funnel plot to assess the influence of publication bias on the pooled analysis. OR, odds ratio; XM, crossmatch.