小剂量螺内酯对透析前慢性肾脏病患者蛋白尿的影响

Effects of low dose Spironolactone on proteinuria in predialysis chronic kidney disease

目的观察小剂量螺内酯在非糖尿病慢性肾脏病(CKD)1～3期患者中的降蛋白尿的作用及其应用的安全性。方法对2010年1月～2011年10月在深圳市第六人民医院肾内科住院及门诊就诊的非糖尿病CKD 1～3期患者55例进行临床观察。按数字随机表法将入选患者随机分为两组。入选者均按慢性肾脏病综合治疗方案处理,并加用贝那普利(10 mg/d)治疗,对照组27例,治疗组28例在原治疗基础上,加用螺内酯(20 mg/d)口服,观察时间为6个月,观察治疗0、3、6个月后患者24 h尿蛋白排泄量、肾功能及血清钾离子水平的变化。结果治疗组中有1例患者在治疗1个月后出现高钾血症(血清K+浓度为6.31 mmol/L)而退出试验;治疗组和对照组治疗3、6个月后24 h尿蛋白定量水平较治疗前均明显下降[治疗组3个月:(1 314±302)mg/24 h vs(2 005±571)mg/24 h,P=0.006;6个月:(1 295±426)mg/24 h vs(2005±571)mg/24 h,P=0.001。对照组3个月:(1 689±603)mg/24 h vs(2 087±636)mg/24 h,P=0.026;6个月:(1 503±598)/24 h vs(2 087±636)mg/24 h,P=0.012];两组治疗6个月后24 h尿蛋白定量水平较同一组治疗3个月后水平无明显下降(P>0.05);治疗组治疗3、6个月后与对照组治疗3、6个月后相比,24 h尿蛋白定量水平低,差异有统计学意义[3个月:(1 314±302)mg/24 h vs(1 689±603)mg/24 h,P=0.033;6个月:(1 295±426)mg/24 h vs(1 503±598)mg/24 h,P=0.027];治疗组治疗3、6个月后血清尿素氮、肌酐水平较治疗前略有上升,估算肾小球滤过率略下降,但与治疗前及对照组治疗3、6个月后上述指标相比差异无统计学意义;治疗组治疗后3、6个月血清钾离子水平略上升[3个月:(4.23±0.41)mmol/L;6个月:(4.27±0.50)mmol/L)],但与治疗前[(4.01±0.44)mmol/L]及对照组治疗3个月[(4.11±0.46)mmol/L]、6个月[(4.16±0.43)mmol/L]后水平相比差异无统计学意义(P>0.05)。结论小剂量螺内酯能降低非糖尿病慢性肾脏病1～3期患者蛋白尿,且其作用独立于其降压及ACEI作用之外,其对血清钾的影响有待进一步的观察。

Objective To observe the effects of low dose Spironolactone on proteinuria and its influence about serum potassium in patients with stage 1-3 chronic kidney disease（CKD）.Methods A total of 55 patients with chronic kidney disease,who were treated in our hospital from January 2010 to October 2011 were enrolled in the present study and randomly divided into two groups.The control group（27 cases） was treated based on routine therapy for CKD and Benazepril（10 mg/d） and the treatment group（28 cases） was treated with Spironolactone（20 mg/d） in addition to the therapy for the control group.24 hours urine protein excretion,systolic pressure,diastolic pressure,blood urea nitrogen（BUN）,blood uric acid（BUA）,serum creatinine（Scr）,estimated glomerular filtration rate（GFR） and serum potassium（K＋） before and after 3,6 months of treatment were measured.Results One patient in the treatment group developed hyperkalemia（K＋ 6.31 mmol/L） after 1 month of treatment and withdrawed from this study.After 3 and 6 months of treatment,24 hours urine protein excretion were decreased in both treatment group and control group [Treatment group： 3 months：（1 314±302） mg/24 h vs（2 005±571） mg/24 h,P = 0.006;6 months：（1 295±426） mg/24 h vs（2 005±571） mg/24 h,P = 0.001.Control group： 3 months：（1 689±603） mg/24 h vs（2 087±636） mg/24 h,P = 0.026;6 months：（1 503±598）/24 h vs（2 087±636） mg/24 h,P = 0.012].The levels of 24 hours urine protein excretion in treatment group after 3 and 6 months of treatment were lower compared with the levels after the same period of treatment in the control group [3 months：（1 314±302） mg/24 h vs（1 689±603） mg/24 h,P = 0.033;6 months：（1 295±426） mg/24 h vs（1 503±598） mg/24 h,P = 0.027].Slightly increase of BUN and Scr and slightly decrease of eGFR were observed in both two groups after 3 and 6 months of treatment,but no statistical significance were observed.Slightly increase of serum potassium levels were observed in the treatment group after 3 and 6 months of treatment [3 months：（4.23±0.41） mmol/L;6 months：（4.27±0.50） mmol/L],but no statistical significance were observed as compared to the same group before treatment [（4.01±0.44） mmol/L] and the control group after the same period of treatment [3 months：（4.11±0.46） mmol/L;6 months：（4.16±0.43） mmol/L）].Conclusion Low dose Spironolactone may reduce proteinuria independent of the effects of blood pressure control and ACEI.More researches are needed to identify the impact of low dose Spironolactone for serum potassium level.