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

<div><p>Background</p><p>High 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.</p><p>Methods and Findings</p><p>PUBMED, 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 (<i>CI</i>) 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% <i>CI</i> −19.65–−10.72, p<1×10⁻⁵), proteinuria (mean difference = −0.73, 95% <i>CI</i> −0.88–−0.57, p<1×10⁻⁵), protein to creatinine ratio (mean difference = −0.22, 95% <i>CI</i> −0.41–−0.03, p = 0.02), and urinary albumin to creatinine ratio (mean difference = −55.38, 95% <i>CI</i> −86.67–<i>−</i>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.</p><p>Conclusion</p><p>In 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></div

Mean differences and 95% <i>CIs</i> of included studies and pooled data for T-type CCBs versus RAS antagonists.

<p>(A) Systolic blood pressure (SBP). (B) Diastolic blood pressure (DBP). (C) The glomerular filtration rate (GFR) in hypertensive patients with proteinuria. (D) Albuminuria in hypertensive patients with proteinuria. (E) The creatinine clearance rate (CCr) in hypertensive patients with proteinuria. (F) Serum creatinine (SCr) in hypertensive patients with proteinuria. (G) Proteinuria.</p

Characteristics of twenty-four studies included in the meta-analysis.

<p>CCBs: Calcium Channel Blockers; RAS: Renin-angiotensin system.</p><p>*Some patients were lost to follow-up or withdrew, and the rate of lost to follow-up was not significantly different between the two groups.</p><p>GRADE Working Group grades of evidence. High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.</p><p>The risk of bias assessment is done using RevMan. Low risk of bias: Plausible bias unlikely to seriously alter the results, low risk of bias for all key domains (within a study), and most information is from studies at low risk of bias (across studies). Unclear risk of bias: That raises some doubt about the results, unclear risk of bias for one or more key domains (within a study), and most information is from studies at low or unclear risk of bias (across studies). High risk of bias: Plausible bias that seriously weakens confidence in the results, high risk of bias for one or more key domains (within a study), the proportion of information from studies at high risk of bias is sufficient to affect the interpretation of results (across studies).</p><p>Characteristics of twenty-four studies included in the meta-analysis.</p

A schematic diagram of the search strategy for published reports.

<p>A schematic diagram of the search strategy for published reports.</p

Mean differences and 95% <i>CIs</i> of included studies and pooled data for T-type CCBs versus L-type CCBs.

<p>(A) Systolic blood pressure (SBP). (B) Diastolic blood pressure (DBP). (C) Glomerular filtration rate (GFR). (D) Serum creatinine (SCr). (E) Aldosterone. (F) Proteinuria in hypertensive patients with CKD. (G) The urinary protein to creatinine ratio in hypertensive patients with CKD. (H) The urinary albumin to creatinine ratio in hypertensive patients with diabetic nephropathy.</p

Funnel plots of odds ratios for all studies in the meta-analyses.

<p>(<b>a</b>) Calcium channel blockers vs Placebo, (<b>b</b>) Calcium channel blockers vs ACEIs, and (<b>c</b>) Calcium channel blockers vs Diuretics or/and β blockers. No evidence of publication bias was found in any of them.</p

A schematic diagram for the search strategy of published reports.

<p>A schematic diagram for the search strategy of published reports.</p

Characteristics of 31 randomized controlled trials included in the meta-analyses.

<p>CCBs: Calcium Channel Blockers; ACEIs: Angiotensin-Converting Enzyme Inhibitors.</p><p>GRADE Working Group grades of evidence (see Supplementary Information online). High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.</p><p>The risk of bias assessment is done using RevMan (see Supplementary Information online). Low risk of bias: Plausible bias unlikely to seriously alter the results, low risk of bias for all key domains (within a study), and most information is from studies at low risk of bias (across studies). Unclear risk of bias: That raises some doubt about the results, unclear risk of bias for one or more key domains (within a study), and most information is from studies at low or unclear risk of bias (across studies). High risk of bias: Plausible bias that seriously weakens confidence in the results, high risk of bias for one or more key domains (within a study), the proportion of information from studies at high risk of bias is sufficient to affect the interpretation of results (across studies).</p