FGF21 and Chronic Kidney Disease

Highlights

• FGF21 is a stress-inducible hormone mainly secreted by the liver that regulates nutrient and metabolic homeostasis.

• FGF21 increases from early-stage CKD and predicts renal progression in diabetes and all-cause mortality in ESRD patients.

• Metabolic disorders, invariably present in CKD, have been proposed to contribute to the elevation of FGF21 levels in CKD.

• Although high FGF21 levels may be advantageous for surviving CKD, excess FGF21 may also have adverse effects on the body.

• FGF21-βklotho endocrine axis might be used as a therapeutic target in CKD patients.

Abstract

The global nephrology community recognizes the increasing burden of kidney disease and its poor health outcomes in the general population. Given this, strategies to establish early diagnosis, improve understanding of the natural course and develop novel therapeutic interventions to slow progression and reduce complications are encouraged. Fibroblast growth factor 21 (FGF21), a member of the endocrine FGF subfamily, has emerged as a master homeostasis regulator of local and systemic lipid, glucose and energy metabolism. In addition, FGF21 should be considered an autonomic and endocrine regulator of stress responses in general. Promising results has been shown in both dysmetabolic animal models and metabolic disease patients after pharmacological administration of FGF21 analogs. The association of FGF21 with renal function has been studied for more than ten years. However, the functional role of FGF21 in the kidney is still poorly understood. This review summarizes the biological effects of FGF21 and discusses what is currently known about this hormone and chronic kidney disease, highlighting important gaps that warrant further research.