KL and renal fibrosis: Klotho was an anti-aging protein that was discovered in 1977 by Japanese scientists.361 Secreted α-Klotho inhibited TGF-β signaling by directly binding to TGFBR2 and ameliorated renal fibrosis.362 However, recombinant full-length Klotho supplement is difficult to apply to CKD patients due to the high cost and difficulties to produce active recombinant full-length Klotho.