In 2015, a phase II randomized double-blind, placebo-controlled clinical trial of CDDO-ME was restarted with 120 CKD patients of Grade 3 or 4, excluding patients bearing risk factors for fluid overload (e.g., high-level BNP and history of heart failure), and the results nicely showed a significant increase in eGFR without any signs of fluid overload (TSUBAKI study; Table 3) [17,18]. This evidence concerns the gene NPPB and heart failure.