Effects of T-Type Calcium Channel Blockers on Renal Function and Aldosterone in Patients with Hypertension: A Systematic Review and Meta-Analysis

Abstract

BackgroundHigh blood pressure can cause kidney damage, which can increase blood pressure, leading to a vicious cycle. It is not clear whether the protective effects of T-type calcium channel blockers (T-type CCBs) on renal function are better than those of L-type CCBs or renin-angiotensin system (RAS) antagonists in patients with hypertension.Methods and FindingsPUBMED, MEDLINE, EMBASE, OVID, Web of Science, Cochrane, CNKI, MEDCH, VIP, and WANFANG databases were searched for clinical trials published in English or Chinese from January 1, 1990, to December 31, 2013. The weighted mean difference (WMD) and 95% confidence interval (CI) were calculated and reported. A total of 1494 reports were collected, of which 24 studies with 1,696 participants (including 809 reports comparing T-type CCBs versus L-type CCBs and 887 reports comparing T-type CCB versus RAS antagonists) met the inclusion criteria. Compared with L-type CCBs, T-type CCBs resulted in a significant decline in aldosterone (mean difference = −15.19, 95% CI −19.65–−10.72, p<1×10−5), proteinuria (mean difference = −0.73, 95% CI −0.88–−0.57, p<1×10−5), protein to creatinine ratio (mean difference = −0.22, 95% CI −0.41–−0.03, p = 0.02), and urinary albumin to creatinine ratio (mean difference = −55.38, 95% CI −86.67–−24.09, p = 0.0005); no significant difference was noted for systolic blood pressure (SBP) (p = 0.76) and diastolic blood pressure (DBP) (p = 0.16). The effects of T-type CCBs did not significantly differ from those of RAS antagonists for SBP (p = 0.98), DBP (p = 0.86), glomerular filtration rate (p = 0.93), albuminuria (p = 0.97), creatinine clearance rate (p = 0.24), and serum creatinine (p = 0.27) in patients with hypertension.ConclusionIn a pooled analysis of data from 24 studies measuring the effects of T-type CCBs on renal function and aldosterone, the protective effects of T-type CCBs on renal function were enhanced compared with L-type CCBs but did not differ from RAS antagonists. Their protective effects on renal function were independent of blood pressure.

P/Q‐type and T‐type voltage‐gated calcium channels are involved in the contraction of mammary and brain blood vessels from hypertensive patients

“…, Abe et al . , Li & Yang ). In agreement with the mibefradil data, NNC 55‐0396 had no significant effect in the undivided patient group, but unfortunately, it was not possible to divide the patients into hypertensive ( n = 5) and normotensive ( n = 1).…”

“…This distribution of calcium channels makes the T-type calcium channels in the kidney important for the regulation of renal haemodynamics (Carmines et al 1993. Clinical studies have confirmed the importance of T-type channels for renal function as treatment of patients with a combined L-and T-type blocker (benidipine) is superior to treatment with conventional calcium blockers (amlodipine) when it comes to not only blood pressure reduction but also lowering albumin/creatinine ratio and attenuation of plasma aldosterone level (Ohishi et al 2007, Ohta et al 2009, Abe et al 2011, Li & Yang 2014, Tani et al 2014. Furthermore, T-type channels might be of significance during cardiovascular disease as T-type channels are upregulated and play a larger role for contraction during augmented oxidative stress (Howitt et al 2013b).…”

Dihydropyridine calcium channel blockers in the elderly with diabetic nephropathy: Are they safe?

“…Recently, a meta-analysis showed that T-type CCBs are more effective than the L-type CCBs in the protection of renal function. 3 The Figure nephropathy with >50% of the participants receiving amlodipine, but patients older than 70 years were excluded. 7,8 In AASK (African American Study of Kidney Disease and Hypertension), patients with diabetes mellitus and those older than 70 years were excluded.…”

Functional importance of T-type voltage-gated calcium channels in the cardiovascular and renal system: news from the world of knockout mice

“…A recent meta-analysis of 24 studies have shown that T-type blockers significantly decline proteinuria and the urinary albumin-to-creatinine ratio compared with L-type blockers, suggesting an important involvement of T-type channels for renal function (61). Altered function of the kidney vascular segments is involved in several pathological conditions, such as diabetes and hypertension (20,96).…”