Histogenomics: association of gene expression patterns with histological parameters in kidney biopsies.

Background: Several studies investigated the association of histologic scores of donor kidney biopsies obtained before engraftment with posttransplant outcomes. Discrimination and goodness of fit of these scores, however, is low.

Methods: Thus, we sought to identify and elucidate the performance of molecular rather than histologic markers for this purpose using whole genome gene expression microarray experiments.

Results: We identified 80 unique differentially regulated genes in 82 samples, showing no histologic damage versus those with histologic damage, based on the Chronic Allograft Damage Index (CADI) and acute tubular injury. Main biological categories enriched with up-regulated genes in damaged tissue were "immunity and defense," "cell communication," or "apoptosis." Interestingly, genes involved in cell structure, cell adhesion, and protein trafficking were specific for tubular atrophy. Histology (CADI score) explained only 14% of the variability of 1 year creatinine (adjusted R2 for panel-reactive antibodies, biopsy confirmed acute rejection, and sum of human leukocyte antigen mismatches) whereas a combination of three biomarkers without clinical covariables explained 28%. The three molecular markers are the NLR family, pyrin domain containing 2 (NLRP2), immunoglobulin J polypeptide, and the regulator of G-protein signaling 5.

Conclusion: In summary, we identified biomarkers in transplant kidney biopsies, which are predictive for medium-term allograft function.