Klotho supplementation reverses renal dysfunction and interstitial fibrosis in remnant kidney.

Introduction: While recent investigations show that klotho exerts reno-protective actions, it has not been fully addressed whether klotho protein supplementation reverses renal damage. Methods: The impacts of subcutaneous klotho supplementation on rats with subtotal nephrectomy were examined. Animals were divided into 3 groups: group1 (short remnant, SR): remnant kidney for 4 weeks, group 2 (long remnant, LR): remnant kidney for 12 weeks and group 3 (klotho supplementation: KL): klotho protein (20 μg/kg/day) supplementation on the remnant kidney. Blood pressure, blood and urine compositions with conventional methods such as enzyme-linked immunosorbent assay and radioimmunoassay, kidney histology and renal expressions of various genes were analyzed. In vitro studies were also performed to support in vivo findings. Results: Klotho protein supplementation decreased albuminuria (-43%), systolic blood pressure (-16%), fibroblast growth factor (FGF) 23 (-51%) and serum phosphate levels (-19%), renal angiotensin II concentration (-43%), fibrosis index (-70%), renal expressions of collagen I (-55%) and transforming growth factor β (-59%) (p