血清VitD代谢物用于评估2型糖尿病性肾病肾功能损伤的回顾性研究

Applying Serum Vitamin D Metabolites in the Assessment of Renal Impairment in Diabetic Kidney Disease of Type 2 Diabetes Mellitus Patients:A Retrospective Study

目的总25(OH)D〔total 25(OH)D,t-25(OH)D〕是传统评价机体维生素D(VitD)的标志物,它包括25(OH)D2和25(OH)D_(3)及C_(3)-差向异构体-25(OH)D_(3)〔C_(3)-epimers-25(OH)D_(3),C_(3)-epi〕。本研究分析血清VitD代谢物与糖尿病肾脏疾病(diabetic kidney disease,DKD)肾功能损伤的关系。方法共计339例研究对象,其中表观健康人群(healthy control,HC)114例、无肾小球滤过功能障碍的2型糖尿病患者(diabetes mellitus,DM)74例和DKD患者151例。采用估算肾小球滤过率(estimated glomerular filtration rate,eGFR)与尿白蛋白/肌酐比值(urine albumin to creatinine ratio,UACR)联合评估方法将DKD组分为4个亚组:stage 2〔DM合并慢性肾脏病(chronic kidney disease,CKD)2期〕、stage 3(DM合并CKD_(3)期)、stage 4(DM合并CKD4期)、stage 5(DM合并CKD5期)。使用超高效液相色谱-串联质谱法(ultra performance liquid chromatography-tandem mass spectrometry,UPLC-MS/MS)检测研究对象25(OH)D2、25(OH)D_(3)以及C_(3)-epi水平,并计算活性VitD_(3)〔the activity level of 25(OH)D_(3),AVitD_(3)〕、t-25(OH)D浓度,25(OH)D2/25(OH)D_(3)比值,C_(3)-epi/t-25(OH)D比值,C_(3)-epi/AVitD_(3)比值。结果DKD组25(OH)D_(3)、t-25(OH)D、AVitD_(3)低于DM组和HC组(P均<0.05);DKD组C_(3)-epi/t-25(OH)D比值、C_(3)-epi/AVitD_(3)比值高于HC组(P均<0.05)。stage 5亚组25(OH)D_(3)、t-25(OH)D、AVitD_(3)和C_(3)-epi低于stage 2和stage 3亚组(P均<0.05);stage 4亚组25(OH)D_(3)、t-25(OH)D、C_(3)-epi低于stage 3亚组(P均<0.05);stage 4亚组25(OH)D_(3)、t-25(OH)D、AVitD_(3)水平低于stage 2亚组(P均<0.05)。结论UPLC-MS/MS法能用于准确评估DKD患者VitD营养状况。DKD患者血清t-25(OH)D、25(OH)D_(3)、AVitD_(3)水平降低,且均随着CKD分期增加而降低。C_(3)-epi与25(OH)D_(3)变化趋势并不一致。

Objective Total 25(OH)D(t-25[OH]D),a marker traditionally used in the assessment of vitamin D(VitD)in the human body,includes 25(OH)D2,25(OH)D_(3),and C_(3)-epimers-25(OH)D_(3)(C_(3)-epi).In this study,we analyzed the relationship between serum VitD metabolites and renal impairment in patients with diabetic kidney disease(DKD).Methods We covered,in the study,339 subjects,including 114 otherwise healthy controls(HC),74 type 2 diabetes mellitus(DM)patients with no glomerular filtration dysfunction,and 151 DKD patients.According to the results of combined evaluation of estimated glomerular filtration rate(eGFR)and urine albumin-to-creatinine ratio(UACR),the DKD patients were further divided into four subgroups,stage 2 subgroup of patients of DM combined with stage-2 chronic kidney disease(CKD2),stage 3 subgroup of patients of DM combined with CKD_(3),stage 4 subgroup of patients of DM combined with CKD4,and stage 5 subgroup of patients of DM combined with CKD5.The levels of 25(OH)D2,25(OH)D_(3),and C_(3)-epi were measured by ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),and the activity level of 25(OH)3(AVitD_(3)),t-25(OH)D concentration,25(OH)D2/25(OH)D_(3)ratio,C_(3)-epi/t-25(OH)D ratio,and C_(3)-epi/AVitD_(3)ratio were calculated.Results The levels of 25(OH)D_(3),t-25(OH)D,and AVitD_(3)were lower in the DKD group than those in the DM and HC groups(all P<0.05).C_(3)-epi/t-25(OH)D ratio and C_(3)-epi/AVitD_(3)ratio were higher in the DKD group than those in the HC group(all P<0.05).The levels of 25(OH)D_(3),t-25(OH)D,AVitD_(3),and C_(3)-epi were lower in the stage 5 subgroup than those in the stage 2 and stage 3 subgroups(all P<0.05).The levels of 25(OH)D_(3),t-25(OH)D,and C_(3)-epi were lower in the stage 4 subgroup than those in the stage 3 subgroup(all P<0.05).The 25(OH)D_(3),t-25(OH)D,and AVitD_(3)levels were lower in the stage 4 subgroup than those in the stage 2 subgroup(all P<0.05).Conclusions UPLC-MS/MS can be used to perform accurate evaluation of VitD nutritional status in DKD patients.DKD patients have decreased levels of serum t-25(OH)D,25(OH)D_(3),and AVitD_(3),all of which progressively decrease along with the rise in CKD staging.The trend of C_(3)-epi and 25(OH)D_(3)changes were not consistent.