复方α酮酸片联合低蛋白饮食延缓慢性肾功能衰竭进展的临床随机对照研究

摘要

目的:随机对照研究比较国产复方酮酸片科罗迪与开同联合低蛋白饮食对延缓慢性肾衰竭(CRF)进展的疗效及安全性. 方法:2010年5月至2010年10月期间选择在南京军区南京总医院全军肾脏病研究所门诊部随访的CRF患者,拟入选60例.要求患者血清肌酐(SCr) 132.6 ～ 265.2 μmol/L,前期随访肾功能相对稳定,无活动性肾脏病变,临床排除继发性肾脏病.所有患者采用常规保肾治疗措施,包括予大黄酸制剂,纠正酸中毒,控制血压[首选钙离子拮抗剂,避免使用血管紧张素转化酶抑制剂(ACEI)及血管紧张素受体拮抗剂(ARB)].采用优质低蛋白饮食,建议患者总蛋白摄入量＜0.6 g/(kg·d).入选后根据信封法随机分为科罗迪组(KLD)及开同(KT)组,分别口服两种复方α酮酸片科罗迪或开同12片/日.患者随访时间为0,2,4,6月.每次随访记录患者主诉,体重、身高及采用生物电阻抗法测量体脂及瘦体重,同时监测血常规、血生化指标及尿检指标. 结果:两组各入选32例患者,其中KLD组脱失2例,KT组脱失l例.余61例患者完成随访.两组患者基线值包括年龄,性别比,体质量指数(BMI),血红蛋白(Hb),SCr,胱抑素C(CysC),24h肌酐清除率(CCr),估测肾小球滤过率(eGFR),尿蛋白量,蛋白摄入量及治疗药物无统计学差异.随访6月期间,所有患者无明显不良反应.与基线值比,随访6月结束时,KLD组及KT组都明显下降的指标包括体重[KLD组(59.0±8.9) kg vs (57.8±8.4) kg；KT组(61.8±11.7)kg vs (60.6±11.3)kg,P＜0.05],血尿酸[KLD组(483.0±84.1)μmol/L vs (439.4±80.1)μmol/L; KT组(484.9±96.1)μmol/L vs(426.1±61.2) μmol/L,P＜0.01]；明显上升的指标包括血钙[KLD组(2.3±0.1)mmol/L vs (2.4±0.1)mmol/L；KT组(2.3±0.2) mmol/Lvs (2.4±0.2) mmol/L,P＜0.01],血免疫球蛋白G(IgG)[KLD组(13.8±2.6)g/Lvs (15.1 ±3.2)g/L；KT组(14.3±2.9)g/Lvs (15.1±3.7) g/L,P＜0.05],尿蛋白定量[KLD组(0.41 ±0.33) g/24h vs (0.79±0.78) g/24h; KT组(0.61±0.53)g/24h vs (0.77±0.59)g/24h,P＜0.01].这些指标两组间无明显差异.随访结束,KT组血清前白蛋白水平显著下降[(376.5±89.5)mg/L vs(318.3 ±77.0) mg/L,P＜0.001],而KLD组下降无统计学差异[(393.0±103.6) mg/L vs(349.4±72.0)mg/L,P＞0.05]；KLD组CCr显著上升[(36.5±13.5) ml/min vs (40.1±14.5) ml/min,P＜0.05],KT组有上升趋势,但无统计学差异[(37.3±17.8)ml/min vs (39.5±17.7)ml/min,P＞0.05].随访结束时两组患者的其他指标包括瘦体重,白蛋白,转铁蛋白,血脂,Hb,SCr,CysC,血磷,eGFR变化无统计学差异. 结论:两种复方α酮酸片联合低蛋白饮食治疗在延缓CRF患者进展及对患者营养指标的影响方面无明显差异,两者均无明显不良反应.%Objective; By a prospective randomized controlled study, to compare the efficacy of low protein diet supplemented with two kinds of ketoanalogues tablets in treatment of patients with chronic renal failure. Methodology: From May,2010 to Oct,2010,the patients diagnosed as chronic renal failure who regularly visited the outpatient department of Jinling hospital were screened for enrolment. The major inclusion criteria were as following; serum creatinine ( SCr) 132rn～265 u,mol/L; stable renal function status without active disease; and primary glomerular disease was supposed to be the primary diagnosis. All patients were recommended to adhere to a diet with protein intake less than 0.6 g/(kg·d) and received the same routine renal protective therapy before being randomly allocated into Keluodi and Ketosteril group supplemented with ketoanalogues tablets Keluodi or Ketosteril, respectively. They were followed at timepoint 0,2,4, and 6th month, for recording of main complains, weight, height and blood and urine tests, as well as body fat and lean weight using bioimpedance analysis method. Results;Each group enrolled 32 patients, with 2 dropouts in Keluodi (KLD) group and 1 dropout in Ketosteril (KT) group. Finally 61 patients were entered into data analysis. There was no difference in baseline values between two groups in age, sex, body mass index, blood hemoglobin,SCr,cystatin C (CysC) , endogenous creatinine clearance (CCr) , estimated glomerular filtration rate (eGFR) , urine proteinexcretion, drugs intake, and diet protein intake (DPI). No obvious side effects were recorded during the follow up period. At the endpoint, compared with baseline, following parameters had significant declined in both group; weight [0 vs 6th month; KLD group (59. 0 ± 8. 9 vs 57. 8 ±8. 4 kg) ,KT group (61. 8 ±11. 7 vs 60. 6 ± 11. 3 kg) ,P <0. 05] ,serum urate [0 vs 6th month:KLD group (483 ± 84. 1 vs 439. 4 ± 80. 1 u,mol/L) , KT group (485±96.1 as 426 ±61. 2 u,mol/L) , P <0. 01 ]; following parameters had significantly elevated in both group; serum calcium [0 vs 6th month; KLD group (2. 3 ±0. 1 vs (2. 4 ±0. 1 mmol/L) ,KT group (2. 3 ±0.2 vs 2. 4 ±0.2 mmol/L) ,P<0. 01] , serum IgG [0 vs 6th month;KLD group(13. 8 ±2.6 vs 15. 1 ±3. 2 g/L) ,KT group ( 14. 3 ±2. 9 vs 15. 1 ±3. 7 g/L) ,P <0. 05] , urine protein excretion (0 vs 6th month;KLD group (0. 41 ± 0. 33 vs (0. 79 ± 0. 78 g/24h) , KT group (0. 61 ± 0. 53 vs 0. 77 ± 0. 59 g/24h) , P < 0. 01 ] ; following parameter had significantly decreased only in KT group but not in KLD group; serum pre-albumin [0 vs 6th month:KT group (376. 5 ± 89. 5 vs 318. 3 ±77. 0 mg/L) ,P <0. 001 ;KLD group (393 ± 104 vs 349. 4 ±72. 0 mg/L) ,P >0. 05] ; following parameter had significantly increased only in KLD group but not in KT group; CCr [0 vs 6th month;KLD group (36. 5 ± 13. 5 vs 40. 1 ± 14. 5 ml/min) ,P<0. 05,KT group (37. 3 ± 17. 8 vs 39. 5 ± 17. 7 ml/min) ,P >0. 05] ; other parameters including body lean weight, serum albumin, serum transferrin, lipids, hemoglobin, SCr, CysC, serum phosphorus and eGFR had no significant changes. Conclusion; Low-protein diet supplemented with two kinds of ketoanalogues tablets has no significant different effects in treatment of patients with chronic renal failure, in regarding nutrition status and renal function preservation, as well as side effects.