Cardio-ankle vascular index is linked to deranged metabolic status, especially high HbA1c and monocyte-chemoattractant-1 protein, in predialysis chronic kidney disease

Int Urol Nephrol. 2020 Jan;52(1):137-145. doi: 10.1007/s11255-019-02336-6. Epub 2019 Nov 26.

Abstract

Introduction and purpose: Arterial stiffness is an independent predictor of cardiovascular disease in chronic kidney disease (CKD). Cardio-ankle vascular index (CAVI) is a newly developed method used to assess arterial stiffness, independent of changes in blood pressure. CAVI reflects stiffness and atherosclerosis at the thoracic, abdominal, common iliac, femoral, and tibial artery levels. In predialysis stage 3-5 diabetic and nondiabetic CKD patients, CAVI levels and its relation to atherosclerosis-associated risk factors including monocyte-chemoattractant protein-1 (MCP-1), sclerostin, fibroblast growth factor-23 (FGF-23), Klotho, and 25-OH vitamin D were determined.

Materials and methods: The study was performed on three age-matched and gender-matched groups. Group 1 included 46 stage 3-5 nondiabetic CKD patients, group 2 included 44 stage 3-5 diabetic CKD patients, and group 3 included 44 non-uremic controls. All subjects underwent CAVI measurement. Serum glycated hemoglobin (HbA1c), total calcium, phosphorus, parathormone, FGF-23, Klotho, MCP-1, sclerostin, and 25-OH vitamin D were determined using standard methods.

Results: CAVI level was 8.22 ± 0.18 m/s in diabetic CKD patients and significantly higher than in nondiabetic CKD (7.61 ± 0.18 m/s) and control (7.59 ± 0.17 m/s) patients. FGF-23 level was higher in the CKD groups than controls but not statistically significant. MCP-1 level was significantly higher in diabetic CKD patients. Klotho and sclerostin levels were significantly lower in diabetic CKD patients. In the whole cohort, CAVI showed positive correlations with age (r = 0.447, p < 0.0001), smoking (r = 0.331, p = 0.035), mean arterial blood pressure (MABP; r = 0.327, p < 0.0001), fasting blood glucose (r = 0.185, p = 0.033), and HbA1c (r = 0.258, p = 0.003). Stepwise regression analysis revealed that age (p = 0.0001, B = 0.461), MABP (p < 0.0001, B = 0.365), HbA1c (p = 0.003, B = 0.251), and MCP-1 (p = 0.013, B = 0.214) independently predicted CAVI levels.

Conclusion: Our results indicate higher CAVI levels, therefore, resulting in increased arterial stiffness in the setting of diabetic CKD. Apart from age and MABP, deranged metabolic status, especially increased HbA1c and MCP-1 levels, is also independently associated with increasing CAVI levels in CKD patients. These results emphasize the importance of metabolic control in the development of arterial stiffness in CKD patients, which is an early predictor of developing cardiovascular complications.

Keywords: Atherosclerosis; CAVI; CKD; DM; Inflammation; MCP-1.

MeSH terms

  • Adaptor Proteins, Signal Transducing / blood
  • Ankle Brachial Index
  • Atherosclerosis / blood*
  • Atherosclerosis / complications
  • Chemokine CCL2 / blood*
  • Diabetes Complications / blood
  • Diabetes Complications / complications*
  • Female
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / blood
  • Glucuronidase / blood
  • Glycated Hemoglobin / metabolism*
  • Humans
  • Klotho Proteins
  • Male
  • Middle Aged
  • Renal Insufficiency, Chronic / blood*
  • Renal Insufficiency, Chronic / complications
  • Vascular Stiffness

Substances

  • Adaptor Proteins, Signal Transducing
  • Chemokine CCL2
  • FGF23 protein, human
  • Glycated Hemoglobin A
  • SOST protein, human
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • Glucuronidase
  • Klotho Proteins