Osteopontin Plays a Critical Role in Interstitial Fibrosis but Not Glomerular Sclerosis in Diabetic Nephropathy

Background/Aims: Osteopontin (OPN) has been implicated in the pathology of several renal conditions. The aim of this study was to clarify the roles of OPN in diabetic nephropathy. Methods: Diabetes mellitus (DM) was induced in wild-type (WT) and OPN knockout (KO) mice by injecting streptozotocin. The mice were killed 20 weeks after induction of DM and their kidneys removed. Results: Renal mRNA expression of OPN was increased in WT-DM mice compared to WT-sham mice. Immunohistochemistry showed high levels of OPN expression in the proximal tubules of WT-DM mice. Kidney weight and urinary albumin excretion increased to similar levels in the WT-DM and KO-DM mice. Interstitial fibrosis was increased in WT-DM mice compared to KO-DM mice. However, there were no differences in the degree of mesangial expansion or glomerular hypertrophy between the two groups. F4/80-positive cells (macrophages) and FSP-1-positive cells (fibroblasts) showed significantly higher infiltration in WT-DM mice than in KO-DM mice. Renal mRNA expression of NADPH oxidase subunits and urinary 8-isoprostane excretion were also increased in WT-DM mice. Conclusions: These results indicated that OPN is a key molecule that induces interstitial fibrosis in the diabetic kidney, but does not induce glomerular sclerosis

HbA1c is an Independent Determinant of Renal Vascular Resistance Estimated by Doppler Sonography in Non-Diabetic Hypertensive Patients

Background Diabetic nephropathy is a progressive disease that leads to renal failure and end stage renal disease. A frequent and early manifestation of diabetic nephropathy is hyaline arteriolosclerosis. The noninvasive method for estimating the severity of arteriolosclerosis is measurement of the renal resistive index (RI). In this study, we determined whether or not normal blood glucose control, classified as an HbA1c < 5.8%, was a sufficiently low level to prevent arteriolosclerosis in patients with essential hypertension. Methods The study subjects were 93 patients with essential hypertension with HbA1c levels <5.8%. Patients with a history of medication for diabetes mellitus were excluded. Blood flow velocity of the renal interlobar arteries was assessed by a Doppler ultrasonography and the RI calculated. Results RI correlated positively with age, body mass index, pulse pressure, pulse rate and HbA1c, and negatively with diastolic blood pressure. A multivariate analysis identified age, pulse pressure and HbA1c as significant independent determinants of RI. Our data show that RI correlates with HbA1c independent of other variables, even in normoglycemic patients with HbA1c levels <5.8%. Conclusions The results of this cross-sectional study suggest that blood glucose levels should be kept as low as possible in order to prevent arteriolosclerosis in the kidney in hypertensive patients