Serum and urinary SOD3 in patients with type 2 diabetes: comparison with early chronic kidney disease patients and association with development of diabetic nephropathy

Am J Physiol Renal Physiol. 2019 Jan 1;316(1):F32-F41. doi: 10.1152/ajprenal.00401.2017. Epub 2018 Oct 10.

Abstract

Extracellular superoxide dismutase 3 (SOD3), one member of the antioxidant defense system and a superoxide scavenger, has been noted to be downregulated in the kidneys of diabetic mice and is characterized by a heparin-binding domain that can anchor the protein to the endothelium and extracellular matrix. The association of the serum and urinary SOD3 levels with diabetic nephropathy in different stages has never been evaluated. It remains unclear how urinary SOD3 changes in different renal diseases. We recruited 98 Taiwanese patients with type 2 diabetes and 10 patients with early chronic kidney disease (CKD) into this study. Biochemical analyses were performed, including evaluation of the serum SOD3, urinary SOD3, urinary albumin, urinary vascular endothelial growth factor (VEGF), and urinary angiotensinogen (ANG). The Kruskal-Wallis rank sum test was used to compare various parameters among the three groups of patients: early CKD, diabetes alone, and diabetes with CKD. Results showed that lower serum and urinary SOD3 levels were observed in the group of patients with diabetes alone. Higher serum and urinary SOD3 levels were observed in the group of patients with diabetes and CKD, which had higher albuminuria and serum creatinine levels. The serum SOD3 levels were significantly positively correlated with renal function, according to the serum creatinine level. The urinary levels of SOD3 were significantly correlated with other urinary biomarkers such as urinary ANG and VEGF. Furthermore, albuminuria can positively predict the serum SOD3 level for the ratio of urinary albumin to urinary creatinine (ACR) >1,190.769 mg/g and the urinary SOD3 level for ACR ≥300 mg/g.

Keywords: albuminuria; angiotensinogen; diabetic nephropathy; extracellular superoxide dismutase; superoxide dismutase 3; vascular endothelial growth factor.

Publication types

  • Comparative Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Albuminuria / blood
  • Albuminuria / enzymology
  • Albuminuria / urine
  • Biomarkers / blood
  • Biomarkers / urine
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / enzymology*
  • Diabetes Mellitus, Type 2 / urine
  • Diabetic Nephropathies / etiology*
  • Endothelium, Vascular / enzymology
  • Female
  • Humans
  • Kidney / enzymology*
  • Kidney / pathology
  • Kidney Tubules / enzymology
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / enzymology*
  • Renal Insufficiency, Chronic / pathology
  • Renal Insufficiency, Chronic / urine
  • Risk Factors
  • Superoxide Dismutase / blood*
  • Superoxide Dismutase / urine*
  • Uric Acid / blood

Substances

  • Biomarkers
  • Uric Acid
  • SOD3 protein, human
  • Superoxide Dismutase