T-type Ca Channel Blockers in Patients with Chronic Kidney Disease in Clinical Practice
Masanori Abe, Kazuyoshi Okada and Masayoshi Soma
Affiliation: 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.
Keywords: Chronic kidney disease, hypertension, T-type calcium channel, T-type calcium channel blocker.
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.
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