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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

  • 摘要:
      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)D3及C3-差向异构体-25(OH)D3〔C3-epimers-25(OH)D3, C3-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CKD3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)D3以及C3-epi水平,并计算活性VitD3 〔the activity level of 25(OH)D3, AVitD3〕、t-25(OH)D浓度,25(OH)D2/25(OH)D3比值,C3-epi/t-25(OH)D比值,C3-epi/AVitD3比值。
      结果   DKD组25(OH)D3、t-25(OH)D、AVitD3低于DM组和HC组(P均<0.05);DKD组C3-epi/t-25(OH)D比值、C3-epi/AVitD3比值高于HC组(P均<0.05)。stage 5亚组25(OH)D3、t-25(OH)D、AVitD3和C3-epi低于stage 2和stage 3亚组(P均<0.05);stage 4亚组25(OH)D3、t-25(OH)D、C3-epi低于stage 3亚组(P均<0.05);stage 4亚组25(OH)D3、t-25(OH)D、AVitD3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)D3、AVitD3水平降低,且均随着CKD分期增加而降低。C3-epi与25(OH)D3变化趋势并不一致。

     

    Abstract:
      Objective  Total 25(OH)D (t-25OHD), a marker traditionally used in the assessment of vitamin D (VitD) in the human body, includes 25(OH)D2, 25(OH)D3, and C3-epimers-25(OH)D3 (C3-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 CKD3, 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)D3, and C3-epi were measured by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and the activity level of 25(OH)3 (AVitD3), t-25(OH)D concentration, 25(OH)D2/25(OH)D3 ratio, C3-epi/t-25(OH)D ratio, and C3-epi/AVitD3 ratio were calculated.
      Results  The levels of 25(OH)D3, t-25(OH)D, and AVitD3 were lower in the DKD group than those in the DM and HC groups (all P<0.05). C3-epi/t-25(OH)D ratio and C3-epi/AVitD3 ratio were higher in the DKD group than those in the HC group (all P<0.05). The levels of 25(OH)D3, t-25(OH)D, AVitD3, and C3-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)D3, t-25(OH)D, and C3-epi were lower in the stage 4 subgroup than those in the stage 3 subgroup (all P<0.05). The 25(OH)D3, t-25(OH)D, and AVitD3 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)D3, and AVitD3, all of which progressively decrease along with the rise in CKD staging. The trend of C3-epi and 25(OH)D3 changes were not consistent.

     

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