Neurological Surgery 脳神経外科52巻6号

2024年11月発行

特集 脳神経外科医が知っておくべき生活習慣病の最新治療

Ⅱ 主な生活習慣病の最新治療

慢性腎臓病関連の最新の研究と治療

著者： 山下純平¹ 田中真司¹ 稲城玲子¹

所属機関： ¹東京大学大学院医学系研究科腎臓・内分泌内科

ページ範囲：P.1206 - P.1214

文献概要

Point
・多くの慢性腎臓病特異的因子と非特異的因子が相互に作用し，慢性腎臓病患者における大脳の構造的および機能的変化に寄与している．
・逆に神経から腎への影響として，迷走神経刺激が急性腎障害の軽減につながることがわかってきている．
・近年登場した新規薬剤としては，慢性腎臓病に対してSGLT2（sodium/glucose cotransporter 2）阻害薬が，2型糖尿病を合併する慢性腎臓病に対してミネラルコルチコイド受容体拮抗薬であるフィネレノンが，腎性貧血に対して低酸素誘導因子-プロリン水酸化酵素阻害薬がそれぞれ適応となった．

参考文献

1）Tanaka S, et al：Crosstalk between the nervous system and the kidney. Kidney Int 97：466-476, 2020

2）Kurella M, et al：Chronic kidney disease and cognitive impairment in the elderly：the health, aging, and body composition study. J Am Soc Nephrol 16：2127-2133, 2005

3）Yaffe K, et al：Chronic kidney disease and cognitive function in older adults：findings from the chronic renal insufficiency cohort cognitive study. J Am Geriatr Soc 58：338-345, 2010

4）Ito S, et al：Strain vessel hypothesis：a viewpoint for linkage of albuminuria and cerebro-cardiovascular risk. Hypertens Res 32：115-121, 2009

5）Chen YC, et al：Chronic kidney disease itself is a causal risk factor for stroke beyond traditional cardiovascular risk factors：a nationwide cohort study in Taiwan. PLoS One 7：e36332, 2012　doi:10.1371/journal.pone.0036332

6）Koren-Morag N, et al：Renal dysfunction and risk of ischemic stroke or TIA in patients with cardiovascular disease. Neurology 67：224-228, 2006

7）Lee M, et al：Low glomerular filtration rate and risk of stroke：meta-analysis. BMJ 341：c4249, 2010　doi:10.1136/bmj.c4249

8）Ninomiya T, et al：Proteinuria and stroke：a meta-analysis of cohort studies. Am J Kidney Dis 53：417-425, 2009

9）Khatri M, et al：Chronic kidney disease is associated with white matter hyperintensity volume：the Northern Manhattan Study（NOMAS）. Stroke 38：3121-3126, 2007

10）Weiner DE, et al：Albuminuria, cognitive functioning, and white matter hyperintensities in homebound elders. Am J Kidney Dis 53：438-447, 2009

11）Seliger SL, et al：Moderate renal impairment and risk of dementia among older adults：the Cardiovascular Health Cognition Study. J Am Soc Nephrol 15：1904-1911, 2004

12）Watanabe K, et al：Cerebro-renal interactions：impact of uremic toxins on cognitive function. Neurotoxicology 44：184-193, 2014

13）De Deyn PP, et al：Nitric oxide in uremia：effects of several potentially toxic guanidino compounds. Kidney Int Suppl 84：S25-S28, 2003

14）D'Hooge R, et al：Involvement of voltage- and ligand-gated Ca2＋ channels in the neuroexcitatory and synergistic effects of putative uremic neurotoxins. Kidney Int 63：1764-1775, 2003

15）Kielstein JT, et al：ADMA increases arterial stiffness and decreases cerebral blood flow in humans. Stroke 37：2024-2029, 2006

16）Kielstein H, et al：Role of the endogenous nitric oxide inhibitor asymmetric dimethylarginine（ADMA）and brain-derived neurotrophic factor（BDNF）in depression and behavioural changes：clinical and preclinical data in chronic kidney disease. Nephrol Dial Transplant 30：1699-1705, 2015

17）Six I, et al：Effects of phosphate on vascular function under normal conditions and influence of the uraemic state. Cardiovasc Res 96：130-139, 2012

18）Jono S, et al：Phosphate regulation of vascular smooth muscle cell calcification. Circ Res 87：E10-E17, 2000　doi:10.1161/01.res.87.7.e10

19）Steitz SA, et al：Smooth muscle cell phenotypic transition associated with calcification：upregulation of Cbfa1 and downregulation of smooth muscle lineage markers. Circ Res 89：1147-1154, 2001

20）Speer MY, et al：Smooth muscle cells give rise to osteochondrogenic precursors and chondrocytes in calcifying arteries. Circ Res 104：733-741, 2009

21）Tyson KL, et al：Osteo/chondrocytic transcription factors and their target genes exhibit distinct patterns of expression in human arterial calcification. Arterioscler Thromb Vasc Biol 23：489-494, 2003

22）Li X, et al：Role of the sodium-dependent phosphate cotransporter, Pit-1, in vascular smooth muscle cell calcification. Circ Res 98：905-912, 2006

23）Crouthamel MH, et al：Sodium-dependent phosphate cotransporters and phosphate-induced calcification of vascular smooth muscle cells：redundant roles for PiT-1 and PiT-2. Arterioscler Thromb Vasc Biol 33：2625-2632, 2013

24）Marebwa BK, et al：Fibroblast growth factor23 is associated with axonal integrity and neural network architecture in the human frontal lobes. PLoS One 13：e0203460, 2018　doi:10.1371/journal.pone.0203460

25）Wright CB, et al：Plasma FGF23 and the risk of stroke：the Northern Manhattan Study（NOMAS）. Neurology 82：1700-1706, 2014

26）Wright CB, et al：Fibroblast growth factor 23 is associated with subclinical cerebrovascular damage：the Northern Manhattan Study. Stroke 47：923-928, 2016

27）Muteliefu G, et al：Indoxyl sulphate induces oxidative stress and the expression of osteoblast-specific proteins in vascular smooth muscle cells. Nephrol Dial Transplant 24：2051-2058, 2009

28）Adijiang A, et al：Indoxyl sulphate promotes aortic calcification with expression of osteoblast-specific proteins in hypertensive rats. Nephrol Dial Transplant 23：1892-1901, 2008

29）Stinghen AE, et al：Differential effects of indoxyl sulfate and inorganic phosphate in a murine cerebral endothelial cell line（bEnd.3）. Toxins（Basel）6：1742-1760, 2014

30）Shroff R, et al：HDL in children with CKD promotes endothelial dysfunction and an abnormal vascular phenotype. J Am Soc Nephrol 25：2658-2668, 2014

31）Zewinger S, et al：HDL cholesterol is not associated with lower mortality in patients with kidney dysfunction. J Am Soc Nephrol 25：1073-1082, 2014

32）Speer T, et al：Abnormal high-density lipoprotein induces endothelial dysfunction via activation of Toll-like receptor-2. Immunity 38：754-768, 2013

33）Holzer M, et al：Uremia alters HDL composition and function. J Am Soc Nephrol 22：1631-1641, 2011

34）Tanaka S, et al：Vagus nerve stimulation activates two distinct neuroimmune circuits converging in the spleen to protect mice from kidney injury. Proc Natl Acad Sci U S A 118：e2021758118, 2021　doi:10.1073/pnas.2021758118

35）山本伸也，柳田素子：腎臓病の病態理解の進歩と最新診療．日内会誌113：452-459, 2024

36）Tanaka S, et al：Sodium-glucose cotransporter 2 inhibition normalizes glucose metabolism and suppresses oxidative stress in the kidneys of diabetic mice. Kidney Int 94：912-925, 2018

37）日本腎臓学会：CKD治療におけるSGLT2阻害薬の適正使用に関するrecommendation．2022　https://jsn.or.jp/medic/data/SGLT2_recommendation20221129.pdf（2024年7月17日アクセス）

38）倉田　遊，他：PHD阻害薬 腎性貧血治療薬としての開発状況ならびに低酸素に対する腎保護薬としての期待．日腎会誌61：490-498, 2019

39）坂下　碧，南学正臣：腎性貧血治療薬HIF-PH阻害薬．日老医誌59：263-274, 2022

40）日本腎臓学会：HIF-PH阻害薬適正使用に関するrecommendation．2020　https://jsn.or.jp/data/HIF-PH_recommendation.pdf（2024年7月17日アクセス）

41）日本腎臓学会（編）：エビデンスに基づくCKD診療ガイドライン2023．東京医学社，東京，2023

42）Sugahara M, et al：Prolyl hydroxylase domain inhibitor protects against metabolic disorders and associated kidney disease in obese type 2 diabetic mice. J Am Soc Nephrol 31：560-577, 2020