A population-based assessment of the familial component of acute kidney allograft rejection

Background. The genetic determinants of acute kidney transplant rejection (AR) are not well studied, and familial aggregation has never been demonstrated. The goal of this retrospective case-control study was to exploit the unique nature of the Utah Population Database (UPDB) to evaluate if AR or rejection-free survival aggregates in families. Methods. We identified 891 recipients with genealogy data in the UPDB with at least one year of follow-up, of which 145 (16.1%) had AR and 77 recipients had biopsy-proven rejection graded ≥ 1A. We compared the genealogical index of familiality (GIF) in cases and controls (i.e. recipients with random assignment of rejection status). Results. We did not find evidence for familial clustering of AR in the entire patient population or in the subgroup with early rejection (n = 52). When the subgroup of recipients with rejection grade ≥ 1A (n = 77) was analysed separately, we observed increased familial clustering (GIF = 3.02) compared to controls (GIF = 1.96), although the p-value did not reach the level of statistical significance (p = 0.17). Furthermore, we observed an increase in familial clustering in recipients who had a rejection-free course (GIF = 2.45) as compared to controls (GIF = 2.08, p = 0.04). When all recipients were compared to non-transplant controls, they demonstrated a much greater degree of familiality (GIF = 2.03 versus GIF 0.63,p < 0.001). Conclusions. There is a familial component to rejection-free transplant course and trend to familial aggregation in recipients with AR grade 1 A or higher. If a genetic association study is performed, there are families in Utah identified in the current study that can be targeted to increase the power of the test.