Remarkably, the compensation to impaired kidney function might promote further progression of CKD through different mechanisms: the phosphate hyperfiltration by functional nephrons leads to tubular damage (57), downregulation of α-Klotho promotes renal fibrosis through increasing TGFβ1 (44) and Wnt (58) signaling pathways, and lower α-Klotho levels might decrease its protective effect on the glomerular filtration barrier (59). The gene discussed is KL; the disease is chronic kidney disease.