title: Soluble serum Klotho in diabetic nephropathy: relationship to VEGF-A.
abstract: OBJECTIVE
  Both kidney expression and soluble serum Klotho are influenced by chronic kidney disease (CKD) and diabetes. Serum Klotho is a yet poorly explored biomarker. We describe, for the first time to our knowledge, serum Klotho in diabetic patients with CKD and its relationship to vascular endothelial growth factor A (VEGF-A).
  
  
  METHODS
  We included 43 controls and 146 diabetic patients with different stages of CKD. Laboratory evaluation, urinary albumin/creatinine ratio (UACR), Klotho (ELISA), VEGF-A (ELISA) were performed.
  
  
  RESULTS
  Klotho was 0.40(0.10-1.30)ng/mL in diabetic patients without CKD and 0.80(0.30-1.30)ng/mL in controls, p=0.20; VEGF-A was higher in diabetic patients 73.85(57.32-119.00)pg/mL than in controls 43.20(30.1-65.9)pg/mL, p<0.0001. Klotho increased with CKD stage: 0.2(0.10-0.40)ng/mL in CKD 1/2, 0.60(0.20-1.1)ng/mL in CKD 3/4 and 1.45(0.425-2.90)ng/mL in dialysis patients, p<0.0001; it also increased with decreasing glomerular filtration rate (GFR). Klotho was lower in albuminuric (UACR>30 mg/g) patients 0.20(0.10-0.70)ng/mL than in normoalbuminuric (UACR<30 mg/g) ones 0.50(0.20-1.30)ng/mL, p=0.03; lowest Klotho was found in microalbuminuric (UACR 30-300 mg/g) patients, p=0.07. VEGF was lower in microalbuminuric patients but was not influenced by GFR. In diabetic patients but not in controls, Klotho correlated to VEGF-A (r=0.29, p=0.0003); in multiple regression VEGF-A was the only significant predictor of Klotho: b=0.27, 95%CI (0.01-0.04), p=0.001.
  
  
  CONCLUSIONS
  In diabetic patients, Klotho is decreased in early CKD and increases thereafter, paralleling reduced GFR. VEGF-A is higher in diabetic patients than in controls. Both Klotho and VEGF-A are decreased in the presence of microalbuminuria. In diabetes, Klotho strongly correlates to VEGF-A.
authors: University of Medicine and Pharmacy Iuliu Hatieganu Cluj Napoca, Department of Nephrology, Romania.
authors: Ina Maria
authors: IM
authors: Kacso
authors: Cosmina Ioana
authors: CI
authors: Bondor
authors: Gabriel
authors: G
authors: Kacso
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000097:blood / Q000503:physiopathology / Q000652:urine; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003404:Creatinine / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D003928:Diabetic Nephropathies / Q000097:blood* / Q000503:physiopathology / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D000090265:Klotho Proteins; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000503:physiopathology / Q000652:urine; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D015415:Biomarkers; D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D008687:Metformin; D003404:Creatinine; D005966:Glucuronidase; D000090265:Klotho Proteins