glucuronyl-glucosamine-glycan-sulfate and Hypertension

Diabetic nephropathy is one of the main causes of end-stage renal disease (ESRD) and is associated with elevated cardiovascular morbidity and mortality.. Current renoprotective treatments for diabetic nephropathy include strict glycemic and optimal blood pressure control, proteinuria/albuminuria reduction and the use of renin-angiotensin-aldosterone system (RAAS) blocking agents. However, the renoprotection provided by these treatments is only partial, calling for more effective approaches.. This review examines emerging strategies for the treatment of diabetic nephropathy, including aggressive RAAS blockade, statins, glitazones, ruboxistaurin, and other promising agents.. In diabetic patients with overt nephropathy, multipharmacological interventions represent a promising way to prevent progression to ESRD. Results of ongoing trials are needed to establish whether the current standard of care of diabetic nephropathy might be improved with these new strategies.

Topics: Aldehyde Reductase; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antibodies, Monoclonal; Diabetic Nephropathies; Drugs, Investigational; Dyslipidemias; Endothelin Receptor Antagonists; Glycosaminoglycans; Humans; Hypertension; Hypoglycemic Agents; Mineralocorticoid Receptor Antagonists; Protein Kinase C; Renin

During arterial hypertension it is often possible to find other factors like lipoidoproteinosis and peripheral arterial disease (POAD), which can accentuate blood rheological abnormalities in hypertensive subjects. A group of hypertensives with lipoidoproteinosis (LP) and POAD were therefore examined to evaluate the relationship between these factors and blood rheological disorders and, if possible, to correct it.. We studied a group of 27 hypertensives with LP and POAD (15 males and 12 females in menopause for at least 1 year, aged 48 +/- 4 years), with WHO stage I hypertension, obesity (BMI = 30 +/- 2), stage II type "a" POAD, class 2 type "b" lipoidoproteinosis (acc. to Fredrick-son's classification) and hyperfibrinogenemia. All patients received oral medication with 500 lipidic units (ULS) sulodexide a day, 20 mg pravastatin o.d. orally, and were put on a low-salt and low-calorie diet (1400 kcal/day) during a follow-up of 60 days. Blood rheology status was evaluated before and after treatment (red blood cell--RBC--deformability and aggregability) using a new computerized instrument, which uses laser rays: the laser assisted optical rotational red cell analyzer (LORCA) (acc. to Hardeman) and RBC deformability using optical microscopy under immersion (acc. to Zipursky and Forconi). Transcutaneous oxymetry was also used to evaluate tissue oxygenation.. At the end of the study a significant improvement (p < 0.01) was noted in the blood rheological patterns of peripheral perfusion and tissue oxygenation. This underlined the positive influence of sulodexide with pravastatin in improving hemorheological patterns and modulating hypercholesterolemia and hyperfibrogenemia in hypertensives with POAD II "a" and LP 2 "b" and blood rheology disorders.

Topics: Adult; Aged; Blood Gas Monitoring, Transcutaneous; Female; Glycosaminoglycans; Hemorheology; Humans; Hypercholesterolemia; Hyperlipidemias; Hypertension; Hypolipidemic Agents; Laser-Doppler Flowmetry; Lasers; Lipoid Proteinosis of Urbach and Wiethe; Male; Middle Aged; Peripheral Vascular Diseases; Pravastatin

Patients with Type 2 diabetes and albuminuria are at high risk to progress to end-stage renal disease (ESRD). Although angiotensin receptor blockers confer renoprotection, many diabetic patients still develop overt nephropathy and reach ESRD. Glycosaminoglycans belong to the same family as heparin and heparinoids. Pilot studies with sulodexide, a glycosaminoglycan, have shown that sulodexide can reduce urinary albumin excretion rates in diabetic patients. No hard renal end-point data are available.. Two multicentre, double-masked, randomized placebo controlled trials were designed to study the renoprotective potential of sulodexide. The Sulodexide Microalbuminuria Trial examined the efficacy of sulodexide given over 26 weeks in 1000 patients with Type 2 diabetes, hypertension and microalbuminuria. The Sulodexide Overt Nephropathy Trial examined the efficacy of sulodexide in 2240 patients with Type 2 diabetes, hypertension and proteinuria > or = 900 mg/24 h.. The primary outcome of The Sulodexide Microalbuminuria Trial was (i) conversion to normoalbuminuria and at least a 25% decrease in the urinary albumin creatinine ratio (UACR), or (ii) at least a 50% reduction in UACR. The primary outcome of The Sulodexide Overt Nephropathy Trial was time to a composite end point of doubling of serum creatinine or ESRD.. The sulodexide nephropathy programme will document whether therapy with sulodexide confers renal protection in Type 2 diabetes and nephropathy.

Topics: Albuminuria; Diabetic Nephropathies; Double-Blind Method; Female; Glycosaminoglycans; Humans; Hypertension; Hypoglycemic Agents; Kidney Failure, Chronic; Male; Treatment Outcome

To assess the effects of different doses and routes of Sulodexide on leukocyte-endothelium interaction and tissue perfusion in a model of venous hypertension and low blood flow.. Subcutaneous and intramuscular treatments with Sulodexide after 2 and 4 weeks, significantly reduced leukocyte rolling and adhesion and increased FCD. Sulodexide did not affect venular diameter and intramuscular treatment was more effective in reducing leukocyte adhesion than the subcutaneous one.. This preliminary study demonstrated that Sulodexide significantly decreased leukocyte-endothelium interaction and improved tissue perfusion in hamsters subjected to venous hypertension and low blood flow.

Topics: Animals; Cricetinae; Disease Models, Animal; Endothelium; Hypertension; Leukocytes; Male; Mesocricetus; Microcirculation; Perfusion