MO389: Klotho Supplementation Reverses Renal Dysfunction and Interstitial Fibrosis in Remnant Kidney

Abstract

Abstract BACKGROUND AND AIMS Several studies demonstrate that klotho shows renoprotective actions. However, it has not been assessed whether klotho supplementation is able to reverse the renal injury. METHOD In the present study, the effects of klotho protein supplementation on remnant rat kidneys were assessed using three groups: renal ablation for 4 weeks, renal ablation for 12 weeks and klotho supplementation (20 μg/kg/day). RESULTS Klotho supplementation suppressed blood pressure, albuminuria, renal renin-angiotensin system (RAS), serum phosphate and fibroblast growth factor (FGF) 23 levels, fibrosis index, renal expression of transforming growth factor β and collagen I. Klotho protein supplementation increased glomerular filtration rate (GFR), fractional excretion of phosphate, renal expression of klotho, bone morphogenetic protein (BMP) 7 and superoxide dismutase. CONCLUSION Our data indicated that klotho supplementation reduced blood pressure and albuminuria with inactivation of renal RAS in the remnant kidney. In addition, exogenous klotho protein supplementation increased endogenous klotho expression, facilitating phosphate excretion with reductions in serum phosphate and FGF23. Finally, klotho protein supplementation upregulated BMP7, at least partly contributing to an increase in GFR and reversal of fibrosis in the remnant kidney.