INS and renal fibrosis: In the ischemia-reperfusion injury (IRI), which is unavoidable to a certain degree in all KTx surgeries, soluble klotho protects renal tubular cells from oxidative damage by inhibiting the insulin/IGF-1 signaling pathway and by inhibition of TGF-β1 for decreasing renal fibrosis [87,88], and upregulation of autophagy in renal tubular cells [3,89].