Soluble serum Klotho in diabetic nephropathy: relationship to VEGF-A

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).

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.

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.

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.