CAJ | 학술논문

目的探讨酮酸联合低蛋白饮食对糖尿病肾病(DN)患者肾脏局部肾素-血管紧张素系统(RAS)活性和足细胞脱落的影响.方法随机选择上海4家医院共68例2型DN患者进入本研究,最终完成疗程且资料完整的患者61例,均属慢性肾脏病3～4期.61例患者被分为低蛋白饮食组(LPD,31例)和酮酸联合低蛋白饮食组(LPD+KA,30例),随访12个月.依据临床及生化等指标评价患者肾功能、尿蛋白和营养状态等改善情况;应用探针荧光定量反转录PCR方法检测患者尿沉渣足细胞标志物nephrin、podocin和synaptopodin的mRNA表达改变;酶联免疫吸附法(ELISA)测定患者尿血管紧张素原(AGT)/肌酐比值.分析酮酸联合低蛋白饮食对DN患者足细胞丢失和尿AGT改变的影响.结果随访12个月后,两组间GFR下降差异无统计学意义(P＞0.05);与LPD组相比,LPD+KA组患者尿蛋白量明显降低(P＜0.01),血清白蛋白和前白蛋白浓度明显升高(P＜0.05).进一步研究发现,患者尿AGT/肌酐比值的基线值与GFR(r=-0.437,P=0.001)、Scr(r=-0.733,P=0.000)、尿蛋白量(r=-0.851,P=0.000)等呈负相关;尿沉渣中podocin和synaptopodin mRNA表达与尿蛋白量呈正相关(r=0.340,P=0.012;r =0.333,P=0.014),与GFR、Scr无相关.随访12个月后,LPD+KA组患者尿AGT/肌酐值明显低于LPD组(P＜0.05);尿沉渣podocin和synaptopodin mRNA的表达显著低于LPD组(P＜0.05).相关分析结果提示,治疗前后尿沉渣podocin和synaptopodin mRNA表达的变化值与尿AGT/肌酐值变化值呈正相关(r=0.305,P=0.026;r=0.281,P=0.04).结论酮酸联合低蛋白饮食的降尿蛋白作用可能与其降低肾脏局部组织RAS活性,抑制足细胞脱落有关.
목적 탐토동산연합저단백음식대당뇨병신병(DN)환자신장국부신소-혈관긴장소계통(RAS)활성화족세포탈락적영향.방법 수궤선택상해4가의원공68례2형DN환자진입본연구,최종완성료정차자료완정적환자61례,균속만성신장병3～4기.61례환자피분위저단백음식조(LPD,31례)화동산연합저단백음식조(LPD+KA,30례),수방12개월.의거림상급생화등지표평개환자신공능、뇨단백화영양상태등개선정황;응용탐침형광정량반전록PCR방법검측환자뇨침사족세포표지물nephrin、podocin화synaptopodin적mRNA표체개변;매련면역흡부법(ELISA)측정환자뇨혈관긴장소원(AGT)/기항비치.분석동산연합저단백음식대DN환자족세포주실화뇨AGT개변적영향.결과 수방12개월후,량조간GFR하강차이무통계학의의(P＞0.05);여LPD조상비,LPD+KA조환자뇨단백량명현강저(P＜0.01),혈청백단백화전백단백농도명현승고(P＜0.05).진일보연구발현,환자뇨AGT/기항비치적기선치여GFR(r=-0.437,P=0.001)、Scr(r=-0.733,P=0.000)、뇨단백량(r=-0.851,P=0.000)등정부상관;뇨침사중podocin화synaptopodin mRNA표체여뇨단백량정정상관(r=0.340,P=0.012;r =0.333,P=0.014),여GFR、Scr무상관.수방12개월후,LPD+KA조환자뇨AGT/기항치명현저우LPD조(P＜0.05);뇨침사podocin화synaptopodin mRNA적표체현저저우LPD조(P＜0.05).상관분석결과제시,치료전후뇨침사podocin화synaptopodin mRNA표체적변화치여뇨AGT/기항치변화치정정상관(r=0.305,P=0.026;r=0.281,P=0.04).결론 동산연합저단백음식적강뇨단백작용가능여기강저신장국부조직RAS활성,억제족세포탈락유관.
Objective To explore the effects of low-protein diet supplemented with ketoacids on podocytes as well as local RAS in the kidney of patients with diabetic nephropathy.Methods A total of 61 patients with T2DN and CKD stages 3-4 were included.All the patients were randomly divided into two groups:low protein group (0.6 g· kg BW-1 · d 1 and 30 kcal · kg BW-1 · d-1,LPD) and LPD +Ketoacids (KA) group (0.6 g·kg BW-1·d-1,30 kcal kg BW-1 ·d-1,and Ketoacids 100 mg·kg BW-1·d-1).Blood and 24 h urine samples were collected at baseline and every 3 months for routine examination to evaluate the efficacy of LPD + KA diet.Podocytes loss was evaluated by mRNA expression of nephrin,podocin,and synaptopodin in urine at baseline and every 3 months.Urinary angiotensinogen was detected by ELISA at baseline and every 3 months.Results After 12 months of follow-up,there were no significant difference statistically in declines of GFR between LPD and LPD+KA group (P ＞ 0.05).Compared with LPD group,proteinuria in LPD+KA group was decreased [(0.43± 0.35) vs (0.15±0.36) g/24 h,P ＜ 0.01].Patients in two groups were both in good nutritional condition,and KA independently increased the levels of serum albumin and prealbumin (all P ＜ 0.05).The urinary angiotensinogen/creatinine ratio was correlated with GFR (r=-0.437,P=0.001),serum creatinine (r=-0.733,P=0.000) and proteinuria (r=-0.851,P=0.000); while urinary mRNA expression of podocyte markers (podocin and synaptopodin were correlated with proteinuria (r =0.340,P =0.012; r =0.333,P =0.014; respectively),but had no correlation with GFR and serum creatinine.After 12 months of follow-up,the urinary angiotensinogen/creatinine ratio in LPD+KA group was lower than in LPD group (P ＜ 0.05).The mRNA expression of podocin and synaptopodin were lower in LPD+ KA group compared with LPD group in urinary sediment (P＜ 0.05).Further correlation analysis suggested that the change of urinary expression of podocin and synaptopodin had a modest but significant correlation with the change urinary angiotensinogen creatinine ratio change (r =0.305,P =0.026; r =0.281,P =0.04,respectively) after treatment for one year.Conclusions Low protein diet supplemented with Ketoacids (LPD + KA) is associated with amelioration of proteinuria,meanwhile nutrition status remains well.The mechanism of these effects may be explained by the role of LPD+KA diet in reducing urine podocyte loss and lowering the angiotensinogen level in the urine.