OBJECTIVE: Clinical studies indicate that the remission, regression or both of nephrotic-range albuminuria are exerted by angiotensin II receptor blockers (ARBs) in diabetes. The current study was performed to test the hypothesis that these effects of ARBs are associated with regression of glomerular podocyte injury. METHODS: We examined the effects of an ARB, olmesartan, on glomerular podocyte injury in type 2 diabetic Otsuka-Long-Evans-Tokushima-Fatty rats with overt albuminuria. RESULTS: At baseline (55-week-old), diabetic Otsuka-Long-Evans-Tokushima-Fatty rats showed severe albuminuria with desmin-positive areas (an index of podocyte injury) in both superficial and juxtamedullary glomeruli, and podocyte injury was much greater in juxtamedullary than in superficial glomeruli. At 75-week-old, Otsuka-Long-Evans-Tokushima-Fatty rats had developed more severe albuminuria and superficial glomerular podocyte injury, whereas juxtamedullary glomerular podocyte injury did not advance further. Olmesartan (10 mg/kg per day) decreased albuminuria and superficial glomerular desmin staining to levels that were lower than those at baseline, whereas advanced juxtamedullary glomerular podocyte injury was not changed. CONCLUSION: The current study demonstrates for the first time that juxtamedullary glomerular podocyte injury reaches a severe condition at an earlier time than superficial glomerular podocyte injury during the progression of overt albuminuria in type 2 diabetic rats. Our data also support the hypothesis that the antialbuminuric effects of ARBs are associated with regression of superficial glomerular podocyte injury in type 2 diabetes with nephrotic-range albuminuria.
OBJECTIVE: Clinical studies indicate that the remission, regression or both of nephrotic-range albuminuria are exerted by angiotensin II receptor blockers (ARBs) in diabetes. The current study was performed to test the hypothesis that these effects of ARBs are associated with regression of glomerular podocyte injury. METHODS: We examined the effects of an ARB, olmesartan, on glomerular podocyte injury in type 2 diabetic Otsuka-Long-Evans-Tokushima-Fattyrats with overt albuminuria. RESULTS: At baseline (55-week-old), diabetic Otsuka-Long-Evans-Tokushima-Fattyrats showed severe albuminuria with desmin-positive areas (an index of podocyte injury) in both superficial and juxtamedullary glomeruli, and podocyte injury was much greater in juxtamedullary than in superficial glomeruli. At 75-week-old, Otsuka-Long-Evans-Tokushima-Fattyrats had developed more severe albuminuria and superficial glomerular podocyte injury, whereas juxtamedullary glomerular podocyte injury did not advance further. Olmesartan (10 mg/kg per day) decreased albuminuria and superficial glomerular desmin staining to levels that were lower than those at baseline, whereas advanced juxtamedullary glomerular podocyte injury was not changed. CONCLUSION: The current study demonstrates for the first time that juxtamedullary glomerular podocyte injury reaches a severe condition at an earlier time than superficial glomerular podocyte injury during the progression of overt albuminuria in type 2 diabeticrats. Our data also support the hypothesis that the antialbuminuric effects of ARBs are associated with regression of superficial glomerular podocyte injury in type 2 diabetes with nephrotic-range albuminuria.
Authors: Kasper Rossing; Per K Christensen; Peter Hovind; Lise Tarnow; Peter Rossing; Hans-Henrik Parving Journal: Kidney Int Date: 2004-10 Impact factor: 10.612
Authors: Aram V Chobanian; George L Bakris; Henry R Black; William C Cushman; Lee A Green; Joseph L Izzo; Daniel W Jones; Barry J Materson; Suzanne Oparil; Jackson T Wright; Edward J Roccella Journal: JAMA Date: 2003-05-14 Impact factor: 56.272
Authors: Y-Y Fan; H Kobori; D Nakano; H Hitomi; H Mori; T Masaki; Y-X Sun; N Zhi; L Zhang; W Huang; B Zhu; P Li; A Nishiyama Journal: Horm Metab Res Date: 2013-01-15 Impact factor: 2.936
Authors: Ruben Rodriguez; Andrew Lee; Keisa W Mathis; Hanna J Broome; Max Thorwald; Bridget Martinez; Daisuke Nakano; Akira Nishiyama; Michael J Ryan; Rudy M Ortiz Journal: Am J Physiol Renal Physiol Date: 2018-07-11