Project Summary As part of the IGNITE II network, the Genetic testing to Understand Renal Disease Disparities in the U.S. (GUARDD-US) clinical trial has been underway since July 2019. GUARDD-US is a prospective randomized pragmatic genotype-guided clinical trial aimed at determining the effect of early vs. delayed knowledge of a positive APOL1 genotyping result on 3- month systolic blood pressure (SBP). African Americans between 18 and 70 years of age with hypertension, with or without chronic kidney disease (CKD) are recruited and randomized to immediate versus delayed return of APOL1 genetic testing. In those who are APOL1 negative, a pilot study to test the impact of pharmacogenetic (PGx) testing on SBP is also underway. The current administrative supplement request reflects a planned increase in enrollment for the GUARDD-US trial. Because the observed prevalence the actionable APOL1 high-risk genotype is significantly lower than projected in the initial sample size calculations (current 14.6% versus 17%), an increase in sample size from 5,435 to 6,600 is required to ensure adequate power for analysis of the primary outcome. In addition, some sites have been unable to meet their recruitment targets, and it is not anticipated that they will make up the shortfall expeditiously. The University of Florida (UF) Clinical Group will support the GUARDD-US increased enrollment request by increasing its enrollment target by 40% (to 700 from 500 participants) and has agreed to add the University of Alabama at Birmingham as a member of its Clinical Group to enroll an additional 300 research participants into the trial.