| Objective:To evaluate quantitatively the manifestations of cerebral small vessel disease(CSVD)and the changes of gray matter volume in patients with chronic kidney disease(CKD)by multimodal MRI,and to analyze the correlation between the changes and clinical and biochemical parameters,expected to further reveal the involvement mechanism of CSVD in patients with CKD.Materials and methods:Thirty-seven patients with CKD admitted to the Department of Nephrology,the First Affiliated Hospital of Dalian Medical University were prospectively collected,including 19 patients with non-dialysis dependent chronic kidney disease(NDD-CKD)and 18 patients with maintaining hemodialysis(HD);and 19 age-,sex-,education-matched normal subjects were recruited as healthy control(HC)in this study from June 2019 to January 2020.At the same time,the clinical and laboratory examination data of patients with CKD were collected.The routine MRI sequence,3D-T1WI,DWI,SWI sequence were performed using the Philips Ingenia CX 3.0T MRI scanner with 32-channel head coil.The lacune,white matter hyperintense(WMH),enlarged perivascular space(EPVS),cerebral microbleed(CMB)were scored and the total burden of CSVD were calculated.SPSS 24.0 was used for data statistical analysis,an One-way analysis of variance(ANOVA)test was used to detect the difference of demographic data among the three groups;Chi-square test was used to detect the difference of classification variables and the incidence among the three groups;the parameters between the two groups was compared by independent sample t-test;The CSVD changes between three groups were analyzed by Kruskal Wallis test.The correlation between MRI and clinical parameters of CKD was analyzed by spearman and multiple logistic regression analysis.The statistical significance was set as P<0.05.The gray matter volume was analyzed by VBM based on SPM12 software package and CAT12 toolbox.ANOVA was used to analysis gray matter volume change between the three groups,the total intracranial volume,age and gender were input as covariates,then t-test was used to analyze the differences between the groups.The mean gray matter volume of all voxels in the abnormal areas based on voxel morphometry were extracted,and the influencing factors of gray matter volume of patients with CKD were analyzed by spearman and multiple linear regression analysis.Results:1.CSVD changes in patients with CKD:The periventricular hyperintense(PVH)in HD group was more serious than that in NDD-CKD and HC group(P=0.030,P<0.001),while for deep white matter hyperintense(DWMH),only HD group and HC group had significant difference(P=0.003).In centrum semiovale(CS),the EPVS scores in HD group were significantly different from those in NDD-CKD and HC group(P=0.012,P<0.001),but in basal ganglia(BG)only in HD group and HC group(P=0.002).The score of lacune in HD group was higher than that in HC group(P=0.024),and the incidence of lacune between HD,NDD-CKD and HC groups was statistically significant(33.3%,21.1%,0%,?~2=11.079,P=0.015).The lacune occurred more frequently in HD group than that in HC group(P=0.008).There were significant differences in the score and incidence of CMB between the three groups(55.6%,31.6%,5.3%,?~2=11.079,P=0.004;H=11.240,P=0.004).The CMB occurred more frequently in HD group than in HC group(P=0.001).There was significant difference between three groups in total burden score of CSVD(H=19.324,P<0.001).The total burden score of CSVD of HD group was higher than HC group(P<0.001).2.Correlation between total burden of CSVD and clinical&laboratory parameters:Spearman correlation analysis showed that total burden of CSVD was correlated with age,SBP,Cystatin C,Hcy,blood urea and creatinine(r=0.532,P=0.001;r=0.453,P=0.005;r=0.441,P=0.006;r=0.327,P=0.048;r=0.425,P=0.009;r=0.440,P=0.006).Multiple logistic regression analysis showed that serum creatinine was still significantly correlated with total burden of CSVD(P=0.032).3.The changes of gray matter volume in Patients with CKD:VBM analysis showed that there were differences in the volume of bilateral insula,left calcarine and cerebellar vermis between the three groups(P<0.05,FWE correction),the volume of bilateral insula,left talus cortex and cerebellar vermis in HD group was lower than that in HC group and NDD-CKD group(P<0.05),but there was no significant difference between NDD-CKD and HC group(P>0.05).4.Correlation between the gray matter volume and clinical&laboratory parameters:the course of disease,cystatin C and the red blood cell distribution width were all related to the gray matter volume of bilateral insular,left calcarine and vermis(r=-0.348,P=0.035;r=-0.336,P=0.042;r=-0.458,P=0.004;r=-0.531,P=0.001;r=-0.600,P<0.001;r=-0.411,P=0.012;r=-0.777,P<0.001;r=-0.544,P<0.001;r=-0.408,P=0.012;r=-0.401,P=0.014;r=-0.476,P=0.003;r=-0.378,P=0.021);The gray matter volume of right insular was correlated with blood urea,creatinine and RBC(r=-0.333,P=0.044;r=-0.457,P=0.004;r=-0.351,P=0.033);The gray matter volume of the left insular was correlated with age and systolic blood pressure(r=-0.466,P=0.004;r=-0.330,P=0.046).The gray matter volume of the left calcarine was correlated with urea and creatinine(r=-0.594,P<0.001;r=-0.672,P<0.001);Gray matter volume of vermis was correlated with serum creatinine(r=-0.375,P=0.022).Linear regression analysis showed that cystatin C was closely correlated with the gray matter volume of the right insular(B=-0.028,95%CI:-0.047?-0.010;P=0.004)and the left calcarine(B=-0.020,95%CI:-0.028?-0.012;P<0.001).5.Correlation analysis of CSVD and gray matter volume changes in patients with CKD:WMH and total burden of CSVD in patients with CKD were significantly negatively correlated with gray matter volume of bilateral insular,left calcarine and vermis(r=-0.451,P=0.005;r=-0.562,P<0.001;r=-0.629,P<0.001;r=-0.449,P=0.005;r=-0.380,P=0.020;r=-0.433,P=0.007;r=-0.405,P=0.013;r=-0.442,P=0.006;r=-0.346,P=0.036;r=-0.442,P=0.009;r=-0.533,P=0.001;r=-0.343,P=0.038),EPVS was negatively correlated with the gray matter volume of the left insular,left calcarine and vermis(r=-0.373,P=0.023;r=-0.331,P=0.046;r=-0.378,P=0.021;r=-0.477,P=0.003;r=-0.359,P=0.029).Lacune and CMB were only negatively correlated with the gray matter volume of left calcarine(r=-0.335,P=0.043;r=-0.340,P=0.039).Conclusion:1.The incidence of CSVD is higher in patients with CKD,and the severity of CSVD is more serious in HD patients;the level of creatinine may be a risk factor of CSVD in patients with CKD.2.Gray matter atrophy occurred in the bilateral insula,left calcarine and cerebellar vermis of patients with CKD,and it was more obvious in HD patients;cystatin C may be a risk factor of gray matter atrophy in patients with CKD.3.The degree of CSVD in patients with CKD was correlated with gray matter atrophy. |
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