OBJECTIVE: Diabetic nephropathy has been considered to be primarily of glomerular origin, but there is now compelling evidence that disruption of the tubulointerstitial architecture determines the outcome of diabetic nephropathy in interplay with the glomerular damage. We investigated whether reactive oxidative species, pro-inflammatory cytokines and endothelial dysfunction were implicated in the progression of tubulointerstitial damage in young subjects with type 1 diabetes. MATERIAL AND METHODS: In a prospective study, we investigated 18 young subjects (mean age 21 years) with type 1 diabetes and microalbuminuria. Quantitative morphometry concerning glomerular and tubulointerstitial changes was performed at baseline (i.e. mean duration of diabetes 10 years) and 2.5 and 8 years later. Markers of endothelial activation and inflammation, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, tumour necrosis factor-alpha, interleukin-6, interleukin-8 and highly sensitive C-reactive protein were measured at baseline and after 8 years. Tissue plasminogen activator antigen and plasminogen activator inhibitor (PAI-1 activity) and asymmetric dimethylargine (ADMA) were measured at baseline and after 2.5 years. RESULTS: PAI-1 activity at baseline was a significant independent variable of the 8-year increment in interstitial volume fraction (Vv(Int/cortex)). ADMA/L-arginine ratio at baseline was associated with the increment in Vv(Int/cortex) during 2.5 years (p<0.01), still significant after adjustment for covariates (p = 0.02). No associations between Vv(Int/cortex) and glomerular parameters, HaemoglobinA1c and urinary albumin excretion were observed. CONCLUSIONS: Biomarkers involved in interstitial volume expansion seem to be different from those of mesangial expansion in early diabetic nephropathy. PAI-1 activity may have a predictive role in the development of the tubulointerstitial expansion.
OBJECTIVE:Diabetic nephropathy has been considered to be primarily of glomerular origin, but there is now compelling evidence that disruption of the tubulointerstitial architecture determines the outcome of diabetic nephropathy in interplay with the glomerular damage. We investigated whether reactive oxidative species, pro-inflammatory cytokines and endothelial dysfunction were implicated in the progression of tubulointerstitial damage in young subjects with type 1 diabetes. MATERIAL AND METHODS: In a prospective study, we investigated 18 young subjects (mean age 21 years) with type 1 diabetes and microalbuminuria. Quantitative morphometry concerning glomerular and tubulointerstitial changes was performed at baseline (i.e. mean duration of diabetes 10 years) and 2.5 and 8 years later. Markers of endothelial activation and inflammation, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, tumour necrosis factor-alpha, interleukin-6, interleukin-8 and highly sensitive C-reactive protein were measured at baseline and after 8 years. Tissue plasminogen activator antigen and plasminogen activator inhibitor (PAI-1 activity) and asymmetric dimethylargine (ADMA) were measured at baseline and after 2.5 years. RESULTS:PAI-1 activity at baseline was a significant independent variable of the 8-year increment in interstitial volume fraction (Vv(Int/cortex)). ADMA/L-arginine ratio at baseline was associated with the increment in Vv(Int/cortex) during 2.5 years (p<0.01), still significant after adjustment for covariates (p = 0.02). No associations between Vv(Int/cortex) and glomerular parameters, HaemoglobinA1c and urinary albumin excretion were observed. CONCLUSIONS: Biomarkers involved in interstitial volume expansion seem to be different from those of mesangial expansion in early diabetic nephropathy. PAI-1 activity may have a predictive role in the development of the tubulointerstitial expansion.
Authors: Vishal S Vaidya; Monika A Niewczas; Linda H Ficociello; Amanda C Johnson; Fitz B Collings; James H Warram; Andrzej S Krolewski; Joseph V Bonventre Journal: Kidney Int Date: 2010-10-27 Impact factor: 10.612
Authors: Amanda C Brodeur; Anna M Roberts-Pilgrim; Kimberlee L Thompson; Craig L Franklin; Charlotte L Phillips Journal: Int J Nephrol Renovasc Dis Date: 2017-08-31
Authors: Sang Soo Kim; Sang Heon Song; In Joo Kim; Yun Kyung Jeon; Bo Hyun Kim; Ihm Soo Kwak; Eun Kyung Lee; Yong Ki Kim Journal: Diabetes Care Date: 2012-10-23 Impact factor: 19.112