Elevated arterial pressure is a major risk factor for progression to ESRD in diabetic nephropathy. However, the component of arterial pressure and level of BP control for optimal renal outcomes are disputed. Data from 1590 hypertensive patients with type 2 diabetes in the Irbesartan Diabetic Nephropathy Trial (IDNT), a randomized, double-blind, placebo-controlled trial performed in 209 clinics worldwide, were examined, and the effects of baseline and mean follow-up systolic BP (SBP) and diastolic BP and the interaction of assigned study medications (irbesartan, amlodipine, and placebo) on progressive renal failure and all-cause mortality were assessed. Other antihypertensive agents were added to achieve predetermined BP goals. Entry criteria included elevated baseline serum creatinine concentration up to 266 mol/L (3.0 mg/dl) and urine protein excretion >900 mg/d. Baseline BP averaged 159/87 ؎ 20/11 mmHg. Median patient follow-up was 2.6 yr. Follow-up achieved SBP most strongly predicted renal outcomes. SBP >149 mmHg was associated with a 2.2-fold increase in the risk for doubling serum creatinine or ESRD compared with SBP <134 mmHg. Progressive lowering of SBP to 120 mmHg was associated with improved renal and patient survival, an effect independent of baseline renal function. Below this threshold, all-cause mortality increased. An additional renoprotective effect of irbesartan, independent of achieved SBP, was observed down to 120 mmHg. There was no correlation between diastolic BP and renal outcomes. We recommend a SBP target between 120 and 130 mmHg, in conjunction with blockade of the renin-angiotensin system, in patients with type 2 diabetic nephropathy.

Plasma selenium (Se), zinc (Zn) and copper (Cu) levels and antioxidant metalloenzymes, glutathione peroxidase (GPX) and superoxide dismutase (SOD), were studied in 17 patients on maintenance hemodialysis (HD) (group I), 14 uremic patients (group II) and 14 healthy subjects (group III). Plasma Se levels and erythrocyte GPX were significantly lower in the HD group (for Se: 0.69 ± 0.12 vs. 1.05 ± 0.13 μmol/l in controls; for erythrocyte GPX: 34.4 ± 6.4 vs. 49.2 ± 9 lU/g hemoglobin in controls) and a significant correlation was found between the two parameters (r = 0.66, p < 0.005). There was also a correlation between decreased plasma Zn and erythrocyte SOD activity (r = 0.58, p < 0.02) and between decreased plasma Cu and erythrocyte SOD (r = 0.60, p < 0.02). Plasma malondialdehyde levels were augmented in HD patients (5.08 ± 0.26 vs. 2.55 ± 0.15 μmol/l in controls and 2.79 ± 0.40 μmol/l in the uremic group). The catalase activity was increased in HD patients (202 ± 24 vs. 140 ± 40 IU/mg hemoglobin in group III). A defective antioxidant activity may thus contribute to increased peroxidative damage to cells in the course of dialysis.

Inability to exercise and large perfusion defects on thallium-201 scan are major predictors of future death and myocardial infarction in high-risk NIDDM patients.

Aims/hypothesis. Proteinuria, reflecting increased glomerular permeability to macromolecules is a characteristic feature of diabetic nephropathy. Nephrin, a 1241-residue transmembrane protein is a key component of the podocyte slit pore membrane and a major contributor of the glomerular filtration barrier. We investigated the expression of nephrin in human kidney tissue from patients with diabetic nephropathy to elucidate its relationship with proteinuria and the effects of anti-proteinuric therapy with angiotensin converting enzyme inhibition. Methods. Renal biopsies were examined from 14 patients with Type II (non-insulin-dependent) diabetes mellitus and proteinuria who had been randomised to receive treatment with the ACE inhibitor, perindopril (4 mg/day) or placebo for the preceding 2 years. These specimens were compared with control human tissue sections, obtained from areas of normal renal cortex following nephrectomy for malignancy. Proteinuria was measured, specimens were examined histologically for injury and the expression of nephrin messenger RNA was assessed by quantitative in situ hybridisation.Results. Glomeruli from placebo-treated patients with diabetic nephropathy, showed a 62% reduction in nephrin expression compared with control subjects (p=0.0003). In contrast, nephrin RNA in glomeruli from perindopril treated patients was similar to that in the non-diabetic control group. In both placebo and perindopril treated patients, a close inverse correlation was noted between the magnitude of nephrin gene expression and the degree of proteinuria (placebo: r=0.86, p=0.013, perindopril: r=0.91, p=0.004). Conclusion/interpretation. Modulation in nephrin expression is related to the extent of proteinuria in diabetic nephropathy. These changes define, at a molecular level alterations in the glomerulus that occur in relation to proteinuria in diabetes and the effects of anti-proteinuric treatment with ACE inhibition. [Diabetologia (2002[Diabetologia ( ) 45:1572[Diabetologia ( -1576