慢性肾脏病患者血清骨硬化蛋白与肌少症相关指标的相关性

Correlation between serum sclerostin and sarcopenia-related indicators in chronic kidney disease patients

目的探讨慢性肾脏病(chronic kidney disease,CKD)患者血清骨硬化蛋白水平与肌少症相关指标的相关性,寻找能兼顾骨质疏松症和肌少症的生物标志物和潜在治疗靶点。方法该研究为单中心横断面研究。收集2021年3月至2023年3月在广州市红十字会医院血液透析中心规律治疗的维持性血液透析患者及CKD 1~5期非透析住院患者的临床资料。采用酶联免疫吸附测定法检测血清骨硬化蛋白水平,测量患者的身高、体重、上臂围、上臂肌围、皮褶厚度、握力、捏力等人体学指标,采用人体成分分析仪测量人体成分指标。根据估算肾小球滤过率以及是否透析将患者分为CKD 1~3期组、CKD 4~5期组及CKD 5期血液透析组。采用单因素方差分析、Kruskal-Wallis H检验及χ^(2)检验比较CKD不同分期组间人口学资料和临床特征的差异。Spearman相关分析、多元线性逐步回归法分析CKD患者血清骨硬化蛋白与肌少症相关指标的相关性。结果该研究纳入CKD 5期血液透析患者104例及CKD 1~5期非透析住院患者104例,年龄为(61.8±13.7)岁,男性114例(54.8%),糖尿病肾病89例(42.8%),肌少症67例(32.2%)。随着肾损伤进展,CKD 1~3期、4~5期、5期血液透析患者血清骨硬化蛋白分别为0.4(0.3,0.9)ng/L、0.5(0.3,1.1)ng/L和1.1(0.6,2.3)ng/L(χ^(2)=8.934,P<0.001),肌少症患病率分别为16.4%(10/61)、34.9%(15/43)和40.4%(42/104)(χ^(2)=10.312,P=0.006)。Spearman相关分析结果显示,血清骨硬化蛋白与估算肾小球滤过率(r=-0.314,P<0.001)、捏力(r=-0.229,P=0.007)、皮褶厚度(r=-0.254,P<0.001)、四肢骨骼肌质量指数(r=-0.169,P=0.010)、人体细胞质量(r=-0.174,P=0.020)及相位角(r=-0.264,P<0.001)均呈负相关,与血磷(r=0.227,P=0.002)和全段甲状旁腺素(r=0.297,P<0.001)均呈正相关;多元线性逐步回归分析结果显示,男性(β=0.330,t=5.675,P<0.001)、血清骨硬化蛋白水平(β=-0.125,t=-2.143,P=0.033)和体重指数(β=0.474,t=8.090,P<0.001)是lg[四肢骨骼肌质量指数]的相关因素。结论血清骨硬化蛋白可作为评价CKD患者肌少症的良好指标及潜在治疗靶点。

Objective To investigate the correlation between serum sclerostin and sarcopenia-related indicators in chronic kidney disease(CKD)patients,and to find biomarkers and potential therapeutic targets that can take into account both osteoporosis and sarcopenia.Methods It was a single-centre cross-sectional study.The clinical data of CKD stage 5 patients undergoing maintenance hemodialysis regularly and CKD stage 1-5 non-dialysis inpatients in the Hemodialysis Centre of Guangzhou Red Cross Hospital from March 2021 to March 2023 were collected retrospectively.The enzyme-linked immunosorbent assay was used to detect the level of serum sclerostin.The anthropometric data such as height,weight,upper arm circumference,upper arm muscle circumference,skinfold thickness,pinch strength and handgrip strength were measured.Body composition analyzer was used to measure the body composition.The patients were divided into CKD stage 1-3 group,CKD stage 4-5 group,and stage 5 hemodialysis group.One-way ANOVA,Kruskal-Wallis H test,and chi-square test were used to compare the differences of demographics and clinical characteristics in different stages of CKD.Spearman correlation analysis and multiple linear stepwise regression analysis were utilized to analyze the correlation between serum sclerostin and sarcopenia-related indicators in CKD patients.Results The study included 104 patients with CKD stage 5 hemodialysis and 104 patients with CKD stage 1-5 non-dialysis patients,with age of(61.8±13.7)years old and 114 males(54.8%).There were 89 patients(42.8%)with diabetic nephropathy and 67 patients(32.2%)with sarcopenia.As renal injury progressed,serum sclerostin levels were 0.4(0.3,0.9)ng/L,0.5(0.3,1.1)ng/L,and 1.1(0.6,2.3)ng/L in patients with CKD stage 1-3,stage 4-5,and stage 5 undergoing hemodialysis(χ^(2)=8.934,P<0.001),and the prevalence of sarcopenia was 16.4%(10/61),34.9%(15/43),and 40.4%(42/104)(χ^(2)=10.312,P=0.006),respectively.Spearman correlation analysis showed that serum sclerostin was negatively correlated with estimated glomerular filtration rate(r=-0.314,P<0.001),pinch strength(r=-0.229,P=0.007),skinfold thickness(r=-0.254,P<0.001),appendicular skeletal muscle index(r=-0.169,P=0.010),body cell mass(r=-0.174,P=0.020),and phase angle(r=-0.264,P<0.001),and positively correlated with serum phosphorus(r=0.227,P=0.002)and intact parathyroid hormone(r=0.297,P<0.001).Multiple linear stepwise regression analysis showed that lg[appendicular skeletal muscle index]was negatively correlated with male(β=0.330,t=5.675,P<0.001)and serum sclerostin(β=-0.125,t=-2.143,P=0.033),and positively correlated with body mass index(β=0.474,t=8.090,P<0.001).Conclusion Serum sclerostin can be used as a good index and a potential therapeutic target for sarcopenia in CKD patients.