AIMS/HYPOTHESIS: Diabetic renal disease has been postulated to progress as a result of an interaction between metabolic and haemodynamic pathways. Our aim was to assess the functional, structural, molecular and cellular aspects of renal disease in an experimental model of diabetes with associated hypertension. METHOD: Streptozotocin-induced diabetic spontaneously hypertensive rats were randomised to no treatment, the ACE inhibitor, perindopril (2 mg/l), the AGE formation inhibitor, aminoguanidine (1 g/l) and a combination of both agents and were followed for 32 weeks. RESULTS: Diabetes was associated with a considerable increase in albumin excretion rate. Both aminoguanidine and perindopril retarded the increase in albuminuria, which was completely abrogated by combination therapy. Glomerulosclerosis and tubulointerstitial damage was reduced by both monotherapies with further renoprotection afforded by combination therapy in both cases. Combination therapy was also associated with a superior restoration in diabetes-induced nephrin protein depletion compared to either monotherapy. TGFbeta1 expression as assessed by in situ hybridisation was increased in the diabetic rats and reduced by perindopril and aminoguanidine. CONCLUSION/ INTERPRETATION: These findings indicate that in the context of diabetes-related renal injury, blocking both the renin-angiotensin and advanced glycation pathways offers superior renoprotection and could be considered as a therapeutic strategy in the prevention and retardation of progressive-diabetic renal injury.
AIMS/HYPOTHESIS: Diabetic renal disease has been postulated to progress as a result of an interaction between metabolic and haemodynamic pathways. Our aim was to assess the functional, structural, molecular and cellular aspects of renal disease in an experimental model of diabetes with associated hypertension. METHOD:Streptozotocin-induced diabetic spontaneously hypertensiverats were randomised to no treatment, the ACE inhibitor, perindopril (2 mg/l), the AGE formation inhibitor, aminoguanidine (1 g/l) and a combination of both agents and were followed for 32 weeks. RESULTS:Diabetes was associated with a considerable increase in albumin excretion rate. Both aminoguanidine and perindoprilretarded the increase in albuminuria, which was completely abrogated by combination therapy. Glomerulosclerosis and tubulointerstitial damage was reduced by both monotherapies with further renoprotection afforded by combination therapy in both cases. Combination therapy was also associated with a superior restoration in diabetes-induced nephrin protein depletion compared to either monotherapy. TGFbeta1 expression as assessed by in situ hybridisation was increased in the diabeticrats and reduced by perindopril and aminoguanidine. CONCLUSION/ INTERPRETATION: These findings indicate that in the context of diabetes-related renal injury, blocking both the renin-angiotensin and advanced glycation pathways offers superior renoprotection and could be considered as a therapeutic strategy in the prevention and retardation of progressive-diabetic renal injury.
Authors: J M Forbes; T Soulis; V Thallas; S Panagiotopoulos; D M Long; S Vasan; D Wagle; G Jerums; M E Cooper Journal: Diabetologia Date: 2001-01 Impact factor: 10.122
Authors: J R Rumble; M E Cooper; T Soulis; A Cox; L Wu; S Youssef; M Jasik; G Jerums; R E Gilbert Journal: J Clin Invest Date: 1997-03-01 Impact factor: 14.808
Authors: Darren J Kelly; Richard E Gilbert; Alison J Cox; Tina Soulis; George Jerums; Mark E Cooper Journal: J Am Soc Nephrol Date: 2001-10 Impact factor: 10.121
Authors: Darren J Kelly; Petri Aaltonen; Alison J Cox; Jon R Rumble; Robyn Langham; Sianna Panagiotopoulos; George Jerums; Harry Holthöfer; Richard E Gilbert Journal: Nephrol Dial Transplant Date: 2002-07 Impact factor: 5.992
Authors: Tiffani N Slaughter; Adrienne Paige; Denisha Spires; Naoki Kojima; Patrick B Kyle; Michael R Garrett; Richard J Roman; Jan M Williams Journal: Am J Physiol Regul Integr Comp Physiol Date: 2013-08-07 Impact factor: 3.619
Authors: M A Zimanyi; K M Denton; J M Forbes; V Thallas-Bonke; M C Thomas; F Poon; M J Black Journal: Diabetologia Date: 2006-02-23 Impact factor: 10.122
Authors: Anna M D Watson; Stephen P Gray; Li Jiaze; Aino Soro-Paavonen; Benedict Wong; Mark E Cooper; Angelika Bierhaus; Raelene Pickering; Christos Tikellis; Despina Tsorotes; Merlin C Thomas; Karin A M Jandeleit-Dahm Journal: Diabetes Date: 2012-06-14 Impact factor: 9.461