Prospective multi-centric study to analyze pre-transplant compatibility algorithm for live-related donor kidney transplant in Indian setting: the "Delhi approach"!

Background: Since no single test is always accurate and sensitive, two or more tests are used to increase the precision of evaluation. Different algorithms have been proposed by centers in Leiden, Basel, Vienna and Minnesota, etc. With an intention to develop an optimal algorithm for India, we evaluated pre-transplant compatibility tests for live-donor kidney transplants. Three tests complement dependent cyto-toxicity cross-match (CDCXM), flow-cytometry cross-match (FCXM) and anti-HLA antibody screening (HAS) were performed and confirmed by the anti-HLA antibody identification (HAI) assay in a multi-centric trial (three transplant centers) in India.

Materials And Methods: All prospective recipients (and their potential donors) underwent low-resolution HLA typing as well as CDCXM, FCXM and HAS assays. In addition, HAI {single antigen bead assay; (SAB)} was done for all recipients to identify possible anti-HLA antibodies. In a virtual cross-match (VXM), antibody specificity was mapped to donor HLA type to determine donor-specific antibodies (DSA). Only patients without DSA were cleared for the transplant. Alternatively, patients with DSA were offered an exchange in the kidney paired donation (KPD) program. The screening results (CDCXM, FCXM, and HAS) were analyzed, individually as well as in combination of screening assays (CDCXM+HAS, CDCXM+FCXM, and FCXM+HAS) and the results were compared with those from the HAI test.

Results: Out of 100 patients, 69 were males and 31 were females; 85 recipients (85%) underwent a kidney transplant. The sensitivity of CDCXM was only 12.1% and the specificity of CDCXM was 100%; whereas the sensitivity of FCXM was 84.8% and the specificity of FCXM was 89.6%. The sensitivity and specificity of class I HAS was 88.2% and 84.3%, respectively. The sensitivity and specificity class II HAS was 88.0% and 80.0%, respectively. However, when both class I/II HAS were tested together the sensitivity increased to 97.0% and the specificity to 82.1%. Similarly, the sensitivity of combined FCXM+HAS had the sensitivity of 100% and the specificity of 76.1%; CDCXM+FCXM had the sensitivity of 84.8% and the specificity of 89.6% and CDCXM+HAS assays reached 97% with the specificity of 82.1%.

Conclusions: Our results showed that the algorithm of FCXM with HAS produced the best sensitivity of 100%. The specificity of 76.1% indicate that the combined FCXM+HAS assays may detect up to 24.9% false positive results. We suggest that these false-positives may be easily resolved by performing the virtual crossmatch based on HAI (SAB) results. In our reflex testing algorithmic approach only 49% patients needed HAI (SAB). Finally, our results suggested that the CDCXM assay may be discontinued in pre-transplant workup owing to its very low sensitivity (12.1%).