Skrha J, Perusicová J, Pont'uch P, Oksa A
Department of Internal Medicine 3, Faculty of Medicine 1, Charles University, Prague, Czech Republic.
Diabetes Res Clin Pract. 1997 Oct;38(1):25-31. doi: 10.1016/s0168-8227(97)00076-4.
Albuminuria is a dominant biochemical feature of developing diabetic nephropathy. A disturbed metabolism of heparan sulphate characterized by an increased loss of anionic charges in the basement membrane has been considered as one of the main factors causing an increased albumin output into urine. All therapeutic approaches inducing a reduction of the albumin excretion rate (AER) have a protective effect on renal function. The effect of glycosaminoglycan sulodexide on albuminuria was studied in a group of 53 diabetic patients (26 Type 1 and 27 Type 2) with micro and macroalbuminuria. Sulodexide (Vessel Due F) was administered intramuscularly in one daily dose (600 lipasemic units) for 3 weeks followed by a 6 week wash-out period. A significant decrease of AER was found in a total cohort of patients following just 1 week of sulodexide treatment (mean 162 micrograms/min, range 10-2708 micrograms/min vs mean 248 micrograms/min, range 20-3160 micrograms/min, P < 0.001). This effect lasted 3-6 weeks after drug withdrawal. Similar results were obtained if Type 1 and Type 2 diabetic patients were evaluated separately but a delay of the AER reduction was observed in the latter group. In all patients the mean AER was reduced to 60-65% of the initial values. A greater effect of sulodexide on albuminuria was observed in patients with AER above 200 micrograms/min than in those with microalbuminuria (a reduction to 47 vs 65% of the initial output). Sulodexide did not significantly reduce albuminuria in 28% of diabetic patients ('non-responders'). In conclusion, glycosaminoglycan sulodexide may reduce AER in patients with micro or macroalbuminuria and it could slow down development of diabetic nephropathy.
蛋白尿是糖尿病肾病发展的主要生化特征。硫酸乙酰肝素代谢紊乱,其特征是基底膜中阴离子电荷损失增加,被认为是导致尿中白蛋白排出量增加的主要因素之一。所有能降低白蛋白排泄率(AER)的治疗方法都对肾功能有保护作用。在一组53例患有微量和大量蛋白尿的糖尿病患者(26例1型和27例2型)中研究了硫酸皮肤素对蛋白尿的影响。硫酸皮肤素(伟素)以每日一次剂量(600脂解单位)肌肉注射,持续3周,随后有6周的洗脱期。仅在硫酸皮肤素治疗1周后,患者总队列中的AER就显著降低(平均162微克/分钟,范围10 - 2708微克/分钟,对比平均248微克/分钟,范围20 - 3160微克/分钟,P < 0.001)。停药后这种效果持续3 - 6周。如果分别评估1型和2型糖尿病患者,也得到了类似结果,但后一组中AER降低出现延迟。在所有患者中平均AER降至初始值的60 - 65%。与微量蛋白尿患者相比,AER高于200微克/分钟的患者中硫酸皮肤素对蛋白尿的影响更大(降至初始排出量的47%对比65%)。28%的糖尿病患者(“无反应者”)中硫酸皮肤素未显著降低蛋白尿。总之,硫酸皮肤素可能降低微量或大量蛋白尿患者的AER,并可能减缓糖尿病肾病的发展。