KL and chronic kidney disease: Additionally, in a rat model of streptozotocin-induced diabetes-associated renal fibrosis, a combination of metformin and a plant extract (from Abelmoschus manihot (L.)medic), traditionally used against CKD, was proved to act in part via the Klotho/TGF-β1/p38MAPK signaling pathway and to significantly lower the weight of the rats with DN, reduce their blood glucose and urine protein level, and the degrees of renal tubule damage, apoptosis, glomerulopathy, and renal fibrosis [57].