Abstract
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PROGRESSION MECHANISM AND TREATMENT OF DIABETIC NEPHROPATHY UPDATE HIROFUMI MAKINO, M.D., PH.D. Director, Okayama University Hospital
Diabetic nephropathy is one of the most serious complications of diabetes. End-stage renal disease (ESRD) due to diabetes is the leading cause and the incidence is very high especially among FRXQWULHV ORFDWHG LQ :HVWHUQ 3DFL¿F 5HJLRQ $FFRUGLQJ WR 865'6 $QQXDO 'DWD 5HSRUW PDQ\ Asian countries headed the list of percentage of incident patients with ESRD, compared to Western countries. Interestingly, Asian countries with high salt intake revealed high incidence of ESRD, meanwhile, Western countries with low salt intake demonstrated low incidence of ESRD. Diabetic nephropathy is characterized by accumulation of extracellular matrix in glomeruli, called exudative, diffuse and nodular lesions. They are finally followed by glomerulosclerosis and LQWHUVWLWLDO ¿EURVLV DQG LQ VXFK VLWXDWLRQ WKH SDWLHQWV LQHYLWDEO\ XQGHUJR GLDO\VLV WKHUDSLHV DQG UHQDO transplantation to survive. :H KDYH EHHQ HPSKDVL]LQJ WKH LPSRUWDQFH RI PLFUR LQÀDPPDWLRQ LQ WKH SURJUHVVLRQ RI GLDEHWLF nephropathy and the identification of key molecules would facilitate to the development of new WKHUDSHXWLF VWUDWHJLHV :H IRFXVHG DQG HPSKDVL]HG RQ WKH DQWL LQÀDPPDWRU\ DQG DQWL R[LGDWLYH HIIHFWV of glucagon-like peptide-1 (GLP-1) receptor agonist and dipeptidyl peptidase-4 (DPP4) inhibitors, which ameliorated the progression of diabetic nephropathy in rodent models. We also investigated the EHQH¿FLDO UROH RI VRGLXP JOXFRVH FRWUDQVSRUWHU 6*/7 LQKLELWRUV RQ WKH SURJUHVVLRQ RI GLDEHWLF nephropathy using various animal models and reported SGLT2 inhibitors primarily ameliorates oxidative stress and inflammation in proximal tubular cells. New therapies such as incretin-related GUXJV DQG 6*/7 LQKLELWRUV ZRXOG KDYH WKH DGGLWLRQDO EHQH¿W LQ WKH SURWHFWLRQ RI GLDEHWLF QHSKURSDWK\ beyond blood glucose control.
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