講演者：　駒場　大峰　（東海大医学部附属病院腎内分泌代謝内科　助教）

演題：　A new rationale for treatment of secondary hyperparathyroidism: from clinical to basic science

日時： 7月13日（水） 12:00-13:00
会場： 発生医学研究所1階　カンファレンス室

Abstract：

Secondary hyperparathyroidism (SHPT) is one of the most serious complications in patients with end-stage renal disease. The widely recognized consequence of SHPT is high-turnover bone disease, which increases bone fragility and the risk of fracture. SHPT also increases the risk of cardiovascular events presumably through increased efflux of calcium and phosphorus from bone. We have recently demonstrated that patients who had undergone parathyroidectomy (PTx) had a significant survival advantage compared with those who had not despite severe SHPT, using data from a nationwide registry of the Japanese Society for Dialysis Therapy (1). Recent clinical trials have also suggested that cinacalcet may reduce the risk of cardiovascular outcomes (2). The potential survival benefit of PTx and cinacalcet may in part be explained by the non-classical actions of FGF23 and PTH. We and others have shown that both PTx and cinacalcet markedly decreases serum FGF23 levels (3,4), and recent experimental data demonstrated that FGF23 causes cardiac hypertrophy (5) and immune dysfunction (6). Furthermore, we and our collaborators have recently shown that PTH drives adipose tissue browning and cachexia in a mouse model of SHPT and adipocyte-specific deletion of PTH/PTHrP receptor attenuated these effects (7). Our data suggest a new mechanism for poor clinical outcomes associated with SHPT and provide additional rationale for suppressing PTH levels in patients with SHPT.

References

1. Komaba H, Taniguchi M, Wada A et al. Parathyroidectomy and survival among Japanese hemodialysis patients with secondary hyperparathyroidism. Kidney Int 88: 350-359, 2015
2. EVOLVE Trial Investigators. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl J Med 367: 2482-2494, 2012
3. Koizumi M, Komaba H, Nakanishi S et al. Cinacalcet treatment and serum FGF23 levels in haemodialysis patients with secondary hyperparathyroidism. Nephrol Dial Transplant 27: 784-790, 2012
4. Takahashi H, Komaba H, Takahashi Y et al. Impact of parathyroidectomy on serum FGF23 and soluble Klotho in hemodialysis patients with severe secondary hyperparathyroidism. J Clin Endocrinol Metab 99: E652-E658, 2014
5. Faul C, Amaral AP, Oskouei B et al. FGF23 induces left ventricular hypertrophy. J Clin Invest 121: 4393-4408, 2011
6. Rossaint J, Oehmichen J, Van Aken H et al. FGF23 signaling impairs neutrophil recruitment and host defense during CKD. J Clin Invest 126: 962-974, 2016
7. Kir S, Komaba H, Garcia AP et al. PTH/PTHrP receptor mediates cachexia in models of kidney failure and cancer. Cell Metab 23: 315-323, 2016

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担当分野： 薬剤学分野　丸山 徹