Klotho supplementation decreases blood pressure and albuminuria in mice with lupus nephritis

Klotho deficiency is prevalent in various chronic kidney diseases. Although klotho is known to bind transforming growth factor (beta(TGF beta) receptor 1 to antagonize renal fibrosis, TGF beta also maintains regulatory T cells with inducing forkhead box protein P3 (FOXP3). Female New Zealand Black/White F-1 (NZBWF1) mice were divided into two groups (n =10 for each): one group was treated with daily subcutaneous injection of klotho protein (30 mu g/kg/day) for 8 weeks, and the other only received vehicle. Klotho supplementation suppressed blood pressure, 8-epi-prostaglandin F2 alpha excretion, albuminuria, and renal angiotensin II levels (p < 0.05 for all) without affecting the glomerular filtration rate (GFR) in NZBWF1 mice. Klotho protein supplementation reduced the number of cluster of differentiation (CD)4+FOXP3+ T cells (p < 0.05) without altering the anti-DNA antibody levels. Klotho supplementation augmented glomerular cellularity, but decreased glomerular crescent formation and interstitial fibrosis in NZBWF1 mice (p < 0.05). Klotho protein supplementation inactivated renal reninangiotensin system, ameliorating blood pressure and albuminuria in NZBWF1 mice. Klotho supplementation hampered regulatory T cells without altering autoantibodies, exerting dual effects on glomerular pathology in NZBWF1 mice without changes in GFR.