Abe Masanori, Okada Kazuyoshi, Soma Masayoshi
Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, 30-1, Oyaguchi Kami-chou, Itabashi-ku, Tokyo 173-8610, Japan.
Curr Hypertens Rev. 2013 Aug;9(3):202-9. doi: 10.2174/1573402110666140131155028.
Chronic kidney disease (CKD) progressively increases the risk of cardiovascular disease (CVD) and end-stage renal disease (ESRD) in line with its severity. Recent studies have revealed that albuminuria and proteinuria in CKD are risk factors for both ESRD and CVD. Accordingly, reductions in albuminuria and proteinuria are associated with a trend in reduced renal death and cardiovascular events. Renin-angiotensin-aldosterone system inhibitors, including angiotensin converting enzyme inhibitors and angiotensin II receptor blockers are recommended as first-choice drugs for the treatment of hypertensive patients with CKD according to several guidelines. However, monotherapy is not sufficient to control blood pressure, particularly in patients with CKD, highlighting the need for combination drug therapy. Calcium channel blockers (CCBs) reduce blood pressure and are useful antihypertensive drugs. Three types of CCBs--the L-, T-, and Ntypes-- are in clinical use. In renal tissue, L-type calcium channels are present only in the afferent arterioles, while N-type and T-type calcium channels are located in both efferent and afferent arterioles. Therefore, CCBs that block either T-type or N-type calcium channels may exert renoprotective effects by dilating the efferent artery and protecting the glomerulus from hyperfiltration injury. It has been established that T-type CCBs exert a renal protective action by ameliorating glomerular microcirculation via vasodilatory activity on both afferent and efferent arterioles. Additionally, blockade of the T-type Ca channel suppresses inflammatory processes, renin-angiotensin-aldosterone system, and oxidative stress. Such effects of T-type CCBs seem to provide good efficacy in terms of the progression of renal outcome and the prevention of cardiovascular events in patients with CKD.
慢性肾脏病（CKD）会随着病情严重程度的增加而逐步提高心血管疾病（CVD）和终末期肾病（ESRD）的发病风险。近期研究表明，CKD中的白蛋白尿和蛋白尿是ESRD和CVD的危险因素。因此，白蛋白尿和蛋白尿的减少与肾脏死亡和心血管事件减少的趋势相关。根据多项指南，肾素-血管紧张素-醛固酮系统抑制剂，包括血管紧张素转换酶抑制剂和血管紧张素II受体阻滞剂，被推荐作为治疗CKD高血压患者的首选药物。然而，单一疗法不足以控制血压，尤其是在CKD患者中，这凸显了联合药物治疗的必要性。钙通道阻滞剂（CCB）可降低血压，是有效的抗高血压药物。临床使用的CCB有三种类型——L型、T型和N型。在肾组织中，L型钙通道仅存在于入球小动脉中，而N型和T型钙通道则位于入球小动脉和出球小动脉中。因此，阻断T型或N型钙通道的CCB可能通过扩张出球小动脉和保护肾小球免受超滤过损伤而发挥肾脏保护作用。已经证实，T型CCB通过对入球小动脉和出球小动脉的血管舒张作用改善肾小球微循环，从而发挥肾脏保护作用。此外，阻断T型钙通道可抑制炎症过程、肾素-血管紧张素-醛固酮系统和氧化应激。T型CCB的这些作用似乎在CKD患者的肾脏预后进展和心血管事件预防方面具有良好疗效。
