Oral sulodexide reduces albuminuria in microalbuminuric and macroalbuminuric type I and type 2 diabetic patients: The Di.NAS randomized trial
Oral sulodexide reduces albuminuria in microalbuminuric and macroalbuminuric type I and type 2 diabetic patients: The Di.NAS randomized trial
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DOI：
10.1097/01.asn.0000014254.87188.e5
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发表时间：
2002-06-01
影响因子：
13.6
通讯作者：
Crepaldi, G
中科院分区：
文献类型：
--
作者：
Gambaro, G;Kinalska, I;Crepaldi, G
糖尿病肾病可通过控制血糖和应用血管紧张素转换酶（ACE）抑制剂来有效预防和治疗。然而，严格的代谢控制可能是困难的。ACE抑制剂的耐受性差，仅部分有效，特别是在2型糖尿病（DM 2）中，从而阻碍了对辅助治疗的研究。舒洛地特是一种糖胺聚糖，是一种在实验研究中显示出肾保护活性的新型药物。D.N.A.S.研究是随机的。一项双盲、安慰剂对照、多中心、剂量范围探索试验，旨在评价糖尿病患者口服舒洛地特的低蛋白尿作用的程度和持续时间。共招募了223名血清肌酐小于或等于150 mumol/L、血压稳定、代谢控制的微量白蛋白尿和大量白蛋白尿DM 1和DM 2患者。他们被随机分配到四个组之一：50 mg/d。100 mg/d。或200 mg/d舒洛地特每日一次或安慰剂治疗4个月（T0至T4），停药后随访4个月（T4至T8）。200 mg/d舒洛地特治疗4个月显著降低对数白蛋白排泄率（logAER），从T0时的5.25 +/- 0.18降至T4时的3.98 +/- 0.11（P < 0.05），并维持至T8（14.11 +/- 0.13：与T0相比P < 0.05）。此外，T4时舒洛地西诱导的AER降低百分比与T4时安慰剂值显著不同，与剂量增量近似线性（30% [置信限，4 - 49%]）。P = 0.03：49% [30 - 63%]。P = 0.0001：舒洛地特50、100和200 mg/d组为74% [64 - 81%]，P = 0.0001。分别T8时，舒洛地特200 mg/d组与安慰剂组相比，AER显著降低62%（45 - 73%）（P = 0.0001）。按糖尿病类型进行的亚组分析（DM 1 vs DM 2、微量白蛋白尿vs大量白蛋白尿或合并使用ACE抑制剂vs未使用ACE抑制剂）显示了相似的结果。这些效果在代谢控制和血压或血清肌酐无微小显著变化的情况下获得。报告的不良事件非常少;无严重不良事件。总之，高剂量舒洛地特4个月疗程可显著改善DM 1和DM 2患者以及伴有或不伴有ACE抑制的微量或大量白蛋白尿患者的白蛋白尿，并呈剂量依赖性。对蛋白尿的作用是持久的，似乎是ACE抑制作用的叠加。
Diabetic nephropathy may be effectively prevented and treated by controlling glycemia and administering angiotensin-converting enzyme (ACE) inhibitors. However, strict metabolic control can be difficult. and ACE inhibitors may be poorly tolerated and only partially effective, particularly in diabetes mellitus type 2 (DM2), warranting the search for ancillary treatment. Sulodexide is a glycosaminoglycan, a new class of drug that has demonstrated nephroprotective activity in experimental investigations. The Di.N.A.S. study was a randomized. double-blind, placebo-controlled, multicenter, dose-range finding trial to evaluate the extent and duration of the hypoalbuminuric effect of oral sulodexide in diabetic patients. A total of 223 microalbuminuric and macroalbuminuric DM1 and DM2 patients with serum creatinine less than or equal to150 mumol/L and stable BP and metabolic control were recruited. They were randomly allocated to one of four groups: 50 mg/d. 100 mg/d. or 200 mg/d sulodexide daily or placebo for 4 mo (T0 to T4), with 4 mo of follow-up after drug suspension (T4 to T8). Treatment with 200 mg/d sulodexide for 4 mo significantly reduced log albumin excretion rate (logAER) from 5.25 +/- 0.18 at TO to 3.98 +/- 0.11 at T4 (P < 0.05), which was maintained till T8 (14.11 +/- 0.13: P < 0.05 versus T0). Moreover, the sulodexide-induced percent reductions in AER at T4 were significantly different front the placebo value at T4 and approximately linear to dose increments (30% [confidence limits, 4 to 49%]. P = 0.03: 49% [30 to 63%]. P = 0.0001: and 74% [64 to 81 %], P = 0.0001 in the sulodexide 50, 100, and 200 mg/d groups. respectively. At T8, the sulodexide 200 mg/d group maintained a 62%, (45 to 73%) AER significant reduction versus placebo (P = 0.0001). Subanalysis by type of diabetes (DM1 versus DM2, microalbuminuric versus macroalbuminuric, or on concomitant ACE inhibitors versits not on ACE inhibitors) demonstrated similar findings. These effects were obtained without tiny significant variation in metabolic control and BP or serum creatinine. Very few adverse events were reported; none were serious. In conclusion, a 4-mo course of high doses of sulodexide significantly and dose-dependently improves albuminuria in DM1 and DM2 patients and micro- or macroalbuminuric patients with or without concomitant ACE inhibition. The effect on albuminuria is long-lasting and seemingly additive to the ACE inhibitory effect.