Overexpression of FGF21 in mice causes disturbed circadian rhythm that can be rescued by specific ablation of KLB in the suprachiasmatic nucleus.358 Some researchers speculate that the circadian rhythm disorder related with high FGF21 level may contribute to the blood pressure fluctuation in CKD patients.36 FGF21 also increases serum corticosterone concentration that has been found to cause depression.359,360 Both depression and high FGF21 are associated with high mortality in dialysis patients.361,362 In brief, FGF21-KLB axis could be a potential treatment target in CKD. Here, KLB is linked to major depressive disorder.