血清尿酸、γ-谷氨酰转移酶与慢性肾脏病发病风险的巢式病例对照研究

Nested case-control study on serum uric acid,serum gamma-glutamyltransferase and the risk of chronic kidney disease

目的探讨金昌队列人群血清尿酸(SUA)、血清γ-谷氨酰转移酶(sGGT)与慢性肾脏病(CKD)发病风险之间的关联,为CKD的防治提供科学依据。方法基于金昌队列,采用巢式病例对照研究方法,选取第1轮随访期间1221名发生CKD的患者作为病例组,按照体检时间(±30 d)、年龄(±2岁)、性别相同1∶1匹配对照组1221名。采用SAS 9.4和R 4.1.2软件对数据进行统计分析。应用条件logistic回归模型分析SUA、sGGT与CKD之间的关联,采用限制性立方样条阐明SUA、sGGT与CKD之间的剂量-反应关系,使用多重线性回归模型探讨SUA与sGGT之间的相关性,然后应用Vanderweele法探讨s GGT在SUA与CKD发病风险关联中的作用。结果调整混杂因素后,条件logistic回归模型结果显示,以e为底自然对数转换后SUA、sGGT与CKD关联的OR值分别为1.96(95%CI:1.28~2.99)、1.24(95%CI:1.07~1.43);SUA、sGGT第四分位发生CKD风险则分别是第一分位的1.36倍(OR=1.36,95%CI:1.02~1.81)、1.32倍(OR=1.32,95%CI:1.01~1.74)。限制性立方样条结果显示,SUA、sGGT与CKD发病风险之间均存在正向线性剂量-反应关系。多重线性回归模型结果显示,在总人群、病例组、对照组中,以e为底自然对数转换后的SUA每增加一个单位,以e为底自然对数转换后sGGT的β分别为0.492(95%CI:0.386~0.599)、0.542(95%CI:0.367~0.682)、0.433(95%CI:0.289~0.577);中介效应分析结果显示,sGGT在SUA与CKD发病风险关联中的中介效应占比为12.65%。结论SUA和sGGT均是CKD发病的独立危险因素,SUA与sGGT作为CKD发病风险的预测因子,对CKD早期预防和高危人群筛选具有重要意义,且SUA与CKD发病风险之间的关联部分由sGGT介导。

Objective To explore the correlation between serum uric acid(SUA),serum gamma-glutamyltransferase(sGGT)and chronic kidney disease(CKD)in Jinchang cohort population,and provide the scientific basis for the prevention and treatment of CKD.Methods Based on the Jinchang cohort,nested case control method was used to select 1221 CKD patients as the case group,and 1221 residents matched by physical examination time(±30 days),age(±2 years),and gender as the control group during the first round of follow-up.SAS 9.4 and R 4.1.2 software were used for statistical analysis.Conditional logistic regression model was used to analyze the correlation between SUA,sGGT and CKD.The dose-response relationships between SUA,s GGT and CKD were analyzed by restricted cubic spline.The correlation between SUA and sGGT was analyzed by multiple linear regression model.Then Vanderweele method was used to explore the role of sGGT in the risk correlation between SUA and CKD.Results After adjusting the confounding factors,the results of conditional logistic regression model showed that the OR of ln-transformed SUA and s GGT for CKD were 1.96(95%CI:1.28-2.99),1.24(95%CI:1.07-1.43),respectively;as compared with the first quartile,the risk of CKD in the fourth quartile of SUA and sGGT were 1.36 times(OR=1.36,95%CI:1.02-1.81),1.32 times(OR=1.32,95%CI:1.01-1.74),respectively.The results of restricted cubic spline showed that there was a positive linear doseresponse relationship between SUA,sGGT and the risk of CKD.The results of multiple linear regression model showed that in the total population,case group and control group,the ln-transformed sGGT increased by 0.492(95%CI:0.386-0.599),0.542(95%CI:0.367-0.682),0.433(95%CI:0.289-0.577)respectively for each unit of increase in ln-transformed SUA;the intermediary effect analysis results showed that the proportion of sGGT intermediary effect in the risk correlation between SUA and CKD was 12.65%.Conclusion Both SUA and sGGT are independent risk factors for CKD incidence,as predictors of CKD incidence risk,SUA and sGGT are of great significance for early prevention of CKD and screening of high-risk population.The correlation between SUA and CKD incidence risk is partially mediated by sGGT.