前列地尔联合贝前列素钠序贯治疗慢性肾脏病

Clinical efficacy and safety of sequential treatment with alprostadil and beraprost sodium for chronic renal failure induced by chronic glomerulonephritis

目的观察前列地尔联合贝前列素钠序贯治疗慢性肾小球肾炎慢性肾衰竭的疗效及安全性。方法 63例慢性肾小球肾炎慢性肾衰竭患者经2周常规治疗导入期后随机分为3组:前列地尔组(n=20,前列地尔注射液10μg/d,2周),前列地尔联合贝前列素钠序贯治疗组(n=21,前列地尔注射液10μg/d,2周,贝前列素钠口服,每天3次,每次20μg,12周),序贯治疗强化组(n=22,前列地尔注射液20μg/d,2周,贝前列素钠口服,每天3次,每次40μg,12周)。检测治疗前后尿白蛋白排泄率、胱抑素C(Cys C)、血尿素氮、血肌酐、纤维蛋白原、D-二聚体、凝血酶原时间(PT)、血小板的变化。计算尿白蛋白排泄率改变率、血肌酐改变率、肾小球滤过率改变率。结果(1)与前列地尔组、序贯治疗组对比,序贯治疗强化组尿白蛋白排泄率改变率下降明显(P<0.01);(2)与前列地尔组对比,序贯治疗组、序贯治疗强化组肾小球滤过率改变率明显上升(P<0.01),序贯治疗强化组改变更加明显,与序贯治疗组对比(P<0.01);(3)与前列地尔组、序贯治疗组对比,序贯治疗强化组血肌酐改变上升率明显减小(P<0.01);(4)经14周治疗后,各治疗组纤维蛋白原、D-二聚体均较治疗前有下降(P<0.05),但各治疗组间无明显差异(P>0.05);(5)经14周治疗后,各治疗组凝血酶原时间(PT)、血小板较治疗前无明显改变(P>0.05)。结论前列地尔联合贝前列素钠序贯治疗可减少尿白蛋白排泄率,改善肾小球滤过率,下降血肌酐上升速率,同时可降低血液纤维蛋白原、D-二聚体浓度,从而延缓慢性肾小球肾炎慢性肾衰竭的进展,与剂量相关,并具有较好的安全性。

Objective To evaluate the clinical efficacy and safety of sequential treatment with alprostadil and beraprost sodium for chronic renal failure caused by chronic glomerulonephritis. Methods Sixty-three patients with chronic renal failure due to chronic glomerulonephrifis, after receiving a 2-week-long conventional treatment, were randomly divided into alprostadil group （n=20, with alprostadil injection at 10μg/d for 2 weeks）, sequential treatment group （n=21, with alprostadil injection at 10 μg/d for 2 weeks and oral beraprost sodium at 20 gg three times a day for 12 weeks）, and strengthened sequential treatment group （n=22, with alprostadil injection at 20μg/d for 2 weeks and a double dose of oral beraprost sodium for 12 weeks）. Urinary albumin excretion rate （UAER）, cystatin C （Cys C）, blood urea nitrogen, creafinine, fibrinogen, D-dimer, prothrombin time （PT）, and platelets were tested before and after the treatment, and the changes in urinary albumin discharge rate, serum creatinine, and glomerular filtration rate were determined. Results The patients in strengthened sequential treatment group showed a significantly decreased change rate of urinary albumin discharge rate （P〈0.01） than those in the other two groups. In the two sequential treatment groups, especially the strengthened treatment group, the change rate of glomerular filtration rate increased significantly compared with that in alprostadil group （P〈0.01）. Strengthened sequential treatment resulted also in significantly decreased increment of serum creatinine compared that in the other 2 groups （P〈0.01）. After 14 weeks of treatment, fibrinogen and D-dimer were decreased in all the 3 groups （P〈0.05） to a comparable level between the 3 groups （P〉 0.05）, and prothrombin time （PT） or platelet showed no significant changes （P〉0.05）. Conclusion Sequential treatment with alprostadil and beraprost sodium can improve the glomerular filtration rate and decrease urine albumin excretion rate, serum creatinine increase rate, and lower blood fibrinogen and D-dimer levels, thus delaying the progression of chronic renal failure caused by chronic glomerulonephritis. This therapy shows a dose-related effect with good clinical safety.