The changes of serum sKlotho and NGAL levels and their correlation in type 2 diabetes mellitus patients with different stages of urinary albumin

Diabetes Res Clin Pract. 2014 Nov;106(2):343-50. doi: 10.1016/j.diabres.2014.08.026. Epub 2014 Sep 16.


Objective: To investigate the changes of serum anti-aging protein Klotho and neutrophil gelatinase-associated lipocalin (NGAL) levels and their correlation in type 2 diabetes mellitus (T2DM) patients at different stages of diabetic kidney disease (DKD) determined by urinary albuminuria.

Methods: 462 cases with T2DM were divided into three groups: normoalbuminuric [N-UAlb; urinary albumin to creatinine ratio (UACR) < 30 mg/g, n=180], microalbuminuric [M-UAlb; UACR 30-300 mg/g, n = 158], macroalbuminuric [L-UAlb; UACR > 300 mg/g, n = 124]. The levels of serum soluble-Klotho (sKlotho), NGAL, 8-isoprostane prostaglandin F2α (8-iso-PGF2α), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) were determined by enzyme-linked immunosorbent assay (ELISA) in all cases and 160 control subjects.

Results: Compared with control, serum sKlotho levels were significantly decreased (P < 0.001), and serum NGAL levels increased significantly (P < 0.001) in T2DM patients. Furthermore, serum sKlotho and NGAL levels were significantly negatively correlated (P < 0.001). Serum sKlotho levels negatively correlated with UACR, TG, CHO, LDL, 8-Iso-PGF2α, MCP-1, TNF-α, TGF-β1 (P < 0.001), but positively correlated with LDL (P < 0.001). Serum NGAL levels positively correlated with UACR, 8-Iso-PGF2α, MCP-1, TNF-α, TGF-β1 (P < 0.001). In addition, serum NGAL levels and LDL were significantly positively correlated (P = 0.005), and HDL was significantly negatively correlated (P < 0.001).

Conclusion: Serum Klotho and NGAL levels may become new biomarkers of the early diagnosis of DKD in T2DM. Klotho may participate in the development of DKD pathological mechanism such as oxidative stress related to inflammation, renal fibrosis, lipid metabolic disorders, modulating the pathological process of diabetic kidney tissue. NGAL may play a part in these mechanisms.

Keywords: Anti-aging protein Klotho; Diabetes mellitus; Diabetic kidney disease; Neutrophil gelatinase-associated lipocalin; Urinary albumin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins
  • Adult
  • Albuminuria / blood*
  • Albuminuria / diagnosis
  • Albuminuria / urine
  • Biomarkers / blood
  • Case-Control Studies
  • Chemokine CCL2 / blood
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / urine
  • Diabetic Nephropathies / blood*
  • Diabetic Nephropathies / diagnosis
  • Diabetic Nephropathies / urine
  • Dinoprost / analogs & derivatives
  • Dinoprost / blood
  • Disease Progression
  • Early Diagnosis
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glucuronidase / blood*
  • Humans
  • Lipocalin-2
  • Lipocalins / blood*
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins / blood*
  • Serum Albumin / metabolism
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha / blood


  • Acute-Phase Proteins
  • Biomarkers
  • Chemokine CCL2
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins
  • Serum Albumin
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • 8-epi-prostaglandin F2alpha
  • Dinoprost
  • Glucuronidase
  • klotho protein