Soluble α-Klotho as a Novel Biomarker in the Early Stage of Nephropathy in Patients with Type 2 Diabetes

Objective: Although alpha-klotho is known as an anti-aging, antioxidant, and cardio-renal protective protein, the clinical implications of soluble alpha-klotho levels in patients with diabetes have not been evaluated. Therefore, this study evaluated whether plasma and urinary alpha-klotho levels are associated with albuminuria in kidney disease in diabetes. Research Design and Methods: A total of 147 patients with type 2 diabetes and 25 healthy control subjects were enrolled. The plasma and urine concentrations of alpha-klotho were analyzed by enzyme-linked immunosorbent assay. Results: Plasma alpha-klotho (572.4 pg/mL [95% CI, 541.9-604.6 pg/mL] vs. 476.9 pg/mL [95% CI, 416.9-545.5 pg/mL]) and urinary alpha-klotho levels (59.8 pg/mg creatinine [95% CI, 43.6-82.0 pg/mg creatinine] vs. 21.0 pg/mg creatinine [95% CI, 9.7-45.6 pg/mg creatinine]) were significantly higher in diabetic patients than non-diabetic controls. Among diabetic patients, plasma alpha-klotho concentration was inversely associated with albuminuria stages (normoalbuminuria, 612.6 pg/mL [95% CI, 568.9-659.6 pg/mL], microalbuminuria, 551.8 pg/mL [95% CI, 500.5-608.3 pg/mL], and macroalbuminuria, 505.7 pg/mL [95% CI, 439.7-581.7 pg/mL] (p for trend = 0.0081), while urinary alpha-klotho levels were remained constantly high with increasing urinary albumin excretion. Conclusions: Soluble alpha-klotho levels in plasma and urine may be novel and useful early markers of diabetic renal injury.