Mechanism of Renal Injury Induced by Metabolic Factors and Prevention of the Injury by Vasoprotective Factors.

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■Hypokalemic Nephropathy(1)We demonstrated an up-regulation of endothelin (ET)-1 production in the cortex and medulla, and an increase in the expression of the ET type A receptor (ETA) and type B receptor (ETB) in the medulla of rats with hypokalemic nephropathy. ETA blockade ameliorated renal tubulointerstitial injury and renal function in hypokalemic nephropathy. ETA blockade ameliorated renal ET-1 production. By contrast, ETB blockade suppressed renal ET-1 production and ETA expression as well as improved renal tubulointerstitial injury and renal ET-1 production and ETA expression as well as improved renal tubulointerstitial injury and renal function in hypokalemic nephropathy. These results suggested that ET-1 can induce renal injury not only via direct activation of ETA, but also by stimulating local production of ET-1 via ETB.(2)We also demonstrated that angiotensin II antagonism ameliorates tubulointerstitial injury and renal function in hypokalemic nephropathy, and suggested that renal angiotensin II generation may contribute to the pathogenesis of hypokalemic tubulointerstitial injury.■Renoprotection by Vasoactive Factors : Adrenomedullin, a potent vasorelaxing peptide and a prosurvival factor for vascular cells, ameliorates tubular necrosis and apoptosis in ischemic reperfusion injury of the kidney possibly by suppressing renal production of TNF-α and interleukin-6.■Searching New Candidate Genes for Diabetic Nephropathy : We found an alteration in the expression of genes related to kidney development and podocyte structure as well as glucose and lipid metabolism and oxidative stress in db/db mice, a model of type 2 diabetes, when compared to the control. This alteration might be related to pathogenesis of early diabetic glomerulopathy.