In this study, we report for the first time that ALD mediates the decreased expression of cldn-5 in GL and cldn-2 and occldn in PT associated to oxidative stress, and the increased expression and phosphorylation of cldn-4 and -8 by a SGK1 and WNK4 signaling pathway in early stages of diabetic nephropathy, this was confirmed by blocking ALD actions with SPL. The gene discussed is CLDN4; the disease is diabetic kidney disease.