Figure 1.

Outlines the mechanistic hypothesis underlying the AMP-FSGS trial. Inhibited AMPK-signaling in the context of FPE promotes glomerulomegaly, podocytopenia, and FSGS, whereas activation of the AMPK signaling pathway by metformin in injured podocytes mitigates podocytopenia and restricts glomerulomegaly promoting an “MCD-like” pathology with better outcomes. Increased AMPK activation enhances prosurvival pathways, including autophagy and improves mitochondrial homeostasis. Therefore, the trial hypothesizes that metformin will activate AMPK, which may serve as a "switch" in injured podocytes, regulating cell survival, and mitigating podocytopenia and FSGS.

AMPK, AMP kinase; MCD, minimal change disease; FPE, foot process effacement; FSGS, focal segmental glomerulosclerosis.