基于数据挖掘分析256例慢性肾脏病肾阳虚证候的演变规律

Evolution Patterns of 256 Cases of Chronic Kidney Disease with Kidney Yang Deficiency Syndrome Based on Data Mining

目的:分析肾阳虚证候在不同慢性肾脏病(CKD)病程阶段和时间演变中的变化特征,从而探索肾阳虚证候在CKD中的演变规律。方法:按照相关标准于2020年10月至2022年9月收集256例CKD患者的证候信息,制定“慢性肾脏病肾阳虚证评价量表”,利用SPSS Statistics 20.0软件、SPSS Modeler 18.0软件、Gephi 0.9.2软件和R 4.2.1软件,采用复杂网络分析、关联规则分析、概率转移矩阵分析和卡方检验等方法对CKD各期人群的证候信息及1周年时的证候变化进行数据挖掘和统计分析,并对各期患者的肾阳虚证进行综合评价。结果:在CKD人群中,女性中的肾阳虚证比例显著高于男性(P<0.01),65岁以上人群中占比高于65岁以下人群,并且随着肾病进展,肾阳虚证人群比例上升,CKD Ⅳ~Ⅴ期人群中的肾阳虚证比例显著高于CKD Ⅰ~Ⅱ期(P<0.01)。CKD Ⅰ~Ⅴ期,暗淡舌频率持续升高,胖大舌和齿痕舌在CKD Ⅲ期以后频率升高,厚苔和腻苔在CKDⅤ期位居频率分布的前3位,在CKD Ⅲ期以后,位居频率分布前3位的全是以肾阳虚证为特征的弱脉、沉脉和细脉。舌脉复杂网络分析显示CKD终末期患者的核心舌脉特征是齿痕舌、白苔、沉脉和细脉。症状频数分析和复杂网络分析结果显示,畏寒喜暖、膝软乏力、形寒肢冷是CKD Ⅰ~Ⅲ期肾阳虚证患者症状频率分布位居前3位的主要症状,在CKD Ⅳ~Ⅴ期,困倦乏力、水肿、夜尿频多等阳虚水泛的表现成为特征性症状。水肿、面色晄白、腰膝酸软、便溏、精神萎靡症状的积分及肾阳虚证总积分随疾病进展逐渐升高,在CKD不同阶段之间差异有统计学意义(P<0.05,P<0.01)。病性证素频数分析显示,随着疾病进展,阳虚证、痰湿证、血瘀证、浊毒证频率逐渐升高并且在CKD不同阶段分布具差异有统计学意义(P<0.05,P<0.01)。复杂网络分析结果显示阳虚证是贯穿CKD各期的核心证素,是CKD的主要证素类型,而痰湿证、血瘀证和浊毒证等兼证在CKD中后期逐渐显现。在CKD肾阳虚证人群中,作为兼夹证的痰湿证、血瘀证和浊毒证在不同CKD阶段的分布具差异有统计学意义(P<0.05,P<0.01),关联规则分析显示,随着疾病进展,痰湿证、血瘀证、浊毒证和饮停证这些兼证与肾阳虚证的关联程度逐渐增强。比较CKD肾阳虚证在1年内的变化情况,结果显示,病位以肾为中心,在脾、胃、心和肝之间传变,肾阳虚证有23.81%的概率向气虚相关证候(脾肾气虚、肝郁脾虚和心气亏虚)转化,23.79%向阴虚相关证候(肝肾阴虚,气阴两虚和肝胃阴虚)转化,9.52%向湿证相关证候(痰湿内阻和风湿痹阻)转化。而脾肾气虚证有20%向肾阳虚证转化,气虚血瘀证有33.33%向肾阳虚证转化。结论:随着CKD Ⅰ期进展到CKD Ⅴ期,肾阳虚症状的严重程度在逐渐加重,肾阳虚证候特征逐渐显著,并且痰湿、血瘀和浊毒等实邪证素在逐渐增多。随着时间的变化,CKD肾阳虚证有向气虚、阴虚和湿证相关证候演变的趋势。这些规律的发现,为CKD辨证论治提供了理论基础和参考指导。

Objective:To analyze the characteristics of kidney Yang deficiency syndrome in different stages and time evolution of chronic kidney disease(CKD)to explore the evolution patterns of kidney Yang deficiency syndrome in CKD.Method:The evidence information of 256 patients with CKD was collected from October 2020 to September 2022 according to relevant standards,and the"Kidney Yang Deficiency Syndrome Evaluation Scale for Chronic Kidney Disease"was developed.With SPSS Statistics 20.0,SPSS Modeler 18.0,Gephi 0.9.2,and R 4.2.1,the syndrome information of CKD patients at various stages and the syndrome changes after one year were statistically analyzed using complex network analysis,association rule analysis,probability transition matrix analysis,and chi-square test,and the kidney Yang deficiency syndrome of patients at various stages was comprehensively evaluated.Result:In the CKD population,the proportion of females with kidney Yang deficiency syndrome was higher than that of males(P<0.01),and the proportion of people over 65 years old was higher than in people under 65 years old.The proportion of people with kidney Yang deficiency syndrome increased with the progression of kidney disease,and the proportion ofⅣ-ⅤCKD patients with kidney Yang deficiency syndrome was higher than that ofⅠ-ⅡCKD patients(P<0.01).FromⅠCKD toⅤCKD,the frequency of dull tongue continued to increase,and the frequency of enlarged tongue and toothmarked tongue continued to increase afterⅢCKD.The frequency of thick coating and greasy coating ranked in the top 3 of frequency distribution inⅤCKD.AfterⅢCKD,the top 3 tongue characteristics were weak pulse,deep pulse,and thready pulse,all of which were characteristics of kidney Yang deficiency syndrome.Complex network analysis of the tongue and pulse showed that the core tongue and pulse characteristics of patients with end-stage CKD were tooth-marked tongue with white coating and deep and thready pulse.The results of symptom frequency analysis and complex network analysis showed that aversion to cold and preference for warmth,weakness of the knees,and cold extremities were the top 3 symptoms inⅠ-ⅢCKD patients with kidney Yang deficiency syndrome,and inⅣ-ⅤCKD,the manifestations of the syndrome of Yang deficiency and water diffusion,such as drowsiness and fatigue,edema,and frequent urination at night became characteristic symptoms.The scores of edema,pale complexion,soreness and weakness of the waist and knees,loose stools,and mental depression symptoms,as well as the total score of kidney Yang deficiency syndrome gradually increased with disease progression,with statistical differences between different stages of CKD(P<0.05,P<0.01).The frequency analysis of disease-related syndrome elements showed that the frequencies of Yang deficiency syndrome,phlegm-dampness syndrome,blood stasis syndrome,and turbidity-toxin syndrome gradually increased with disease progression,and there were statistically significant differences in the distribution between different stages of CKD(P<0.05,P<0.01).The results of complex network analysis showed that Yang deficiency syndrome was the core syndrome element throughout all stages of CKD and was the main syndrome element type of CKD,while phlegm-dampness syndrome,blood stasis syndrome,and turbiditytoxin syndrome were gradually revealed in the middle and late stages of CKD.In the CKD population with kidney-Yang deficiency syndrome,the distribution of phlegm-dampness syndrome,blood stasis syndrome,and turbidity-toxin syndrome as concurrent syndromes in different CKD stages had statistically significant differences(P<0.05,P<0.01).The association rule analysis showed that as the disease progressed,associations between the concurrent syndromes,such as phlegm-dampness syndrome,blood stasis syndrome,turbidity-toxin syndrome,and fluid retention syndrome,and kidney-Yang deficiency syndrome were gradually enhanced.The comparison of the changes in CKD with kidney Yang deficiency syndrome within one year showed that the disease location was centered on the kidney and transmitted between the spleen,stomach,heart,and liver.There is a 23.81%probability of kidney-Yang deficiency syndrome transforming into Qi deficiency syndromes(Qi deficiency in the spleen and kidney,Qi deficiency in the liver,and Qi deficiency in the heart),23.79%into Yin deficiency syndromes(Yin deficiency in the liver and kidney,Qi and Yin deficiency,and Yin deficiency in the liver and stomach),and 9.52%into dampness syndromes(phlegm-dampness internal obstruction and wind-dampness obstruction).In contrast,20%of spleen and kidney Qi deficiency syndrome transformed into kidney Yang deficiency syndrome,and 33.33%of Qi deficiency and blood stasis syndrome transformed into kidney Yang deficiency syndrome.Conclusion:AsⅠCKD progresses toⅤCKD,the severity of kidney Yang deficiency syndrome gradually increases,and the syndrome characteristics of kidney Yang deficiency become pronounced.Furthermore,the pathogenic factors,such as phlegm-dampness,blood stasis,and turbidity-toxin,gradually increase.With the change of time,kidney Yang deficiency syndrome in CKD tends to evolve into syndromes related to Qi deficiency,Yin deficiency,and dampness.The discovery of these rules provides a theoretical basis and reference guidance for the treatment of CKD based on syndrome differentiation.