Antiproteinuric effect of the calcium channel blocker cilnidipine added to renin-angiotensin inhibition in hypertensive patients with chronic renal disease

Fujita, Toshiro; Ando, Katsuyuki; Nishimura, Hideki; Ideura, Terukuni; Yasuda, Gen; Isshiki, Masashi; Takahashi, K.

doi:10.1038/sj.ki.5002623

Cited by 132 publications

(127 citation statements)

References 39 publications

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“…5,8 The Cilnidipine vs. Amlodipine Randomized Trial for Evaluation in Renal Disease study showed that cilnidipine was more beneficial than amlodipine in hypertensive patients. 7 Besides RAS inhibition, strict control of BP is considered important for preventing the progression of kidney disease. 15,17,18 Both cilnidipine and amlodipine effectively reduced BP level in hypertensive patients after 6 months of treatment.…”

Section: Discussionmentioning

confidence: 99%

“…3,6 Furthermore, cilnidipine was shown to be more beneficial than amlodipine in combined treatment for hypertensive patients with kidney disease and significant proteinuria who were receiving treatment with a renin-angiotensin system (RAS) inhibitor. 7 The beneficial effect of cilnidipine might be attributable to the inhibition of renal sympathetic nerve activity 8 and reduction of glomerular hypertension (because of the vasodilation of efferent arterioles), which are consequences of the N-type calcium channel blockade. However, the precise mechanism underlying the renoprotective effect of cilnidipine remains unknown.…”

Section: Introductionmentioning

confidence: 99%

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Renoprotective and antioxidant effects of cilnidipine in hypertensive patients

Soeki

Kitani²,

Kusunose

et al. 2012

Hypertens Res

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Cilnidipine, an L/N-type calcium channel blocker (CCB), has been reported to have more beneficial effects on proteinuria progression in hypertensive patients than amlodipine, an L-type CCB. The N-type calcium channel blockade that inhibits renal sympathetic nerve activity might reduce glomerular hypertension by facilitating vasodilation of the efferent arterioles. However, the precise mechanism of the renoprotective effect of cilnidipine remains unknown. Because cilnidipine exerted significantly higher antioxidant activity than amlodipine in cultured human mesangial cells, we hypothesized that cilnidipine might exert a renoprotective effect by suppressing oxidative stress. A total of 35 hypertensive patients receiving a renin-angiotensin system inhibitor were randomly assigned to a cilnidipine (n ¼ 18; 10 mg per day cilnidipine titrated to 20 mg per day) or amlodipine (n ¼ 17; 5 mg per day amlodipine titrated to 10 mg per day) group; the target blood pressure (BP) was set at 130/85 mmHg. After 6 months of treatment, systolic and diastolic BPs were significantly reduced in both of the groups, without any significant difference between the groups. The urinary albumin, 8-hydroxy-2 0 -deoxyguanosine (OHdG) and liver-type fatty-acid-binding protein (L-FABP) to creatinine ratios significantly decreased in the cilnidipine group (Po0.05) compared with those in the amlodipine group. The reductions in urinary albumin, 8-OHdG and L-FABP were not correlated with the change in systolic BP. In conclusion, cilnidipine, but not amlodipine, ameliorated urinary albumin excretion and decreased urinary 8-OHdG and L-FABP in the hypertensive patients. Cilnidipine probably exerts a greater renoprotective effect through its antioxidative properties.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Renoprotective and antioxidant effects of cilnidipine in hypertensive patients

Soeki

Kitani²,

Kusunose

et al. 2012

Hypertens Res

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“…CCBs, however, can be divided into several subtypes. Cilnidipine, which is reported to protect against cardiovascular [27][28][29] and kidney disease, [30][31][32] works in a variety of ways, including blocking the N-type calcium channel and the L-type calcium channel. Recently, cilnidipine has also been reported to suppress renin activity and inhibit the renal renin-angiotensin system.…”

Section: Cilnidipine and Osteoporosis Hideo Shimizu Et Almentioning

confidence: 99%

Cilnidipine, but not amlodipine, ameliorates osteoporosis in ovariectomized hypertensive rats through inhibition of the N-type calcium channel

et al. 2011

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Both osteoporosis and high blood pressure are major diseases in aging populations. Recent studies demonstrated that some antihypertensive drugs reduced the risk of bone fracture in elderly patients. Although calcium channel blockers (CCB) are widely used as first-line antihypertensive agents, there is no evidence that they prevent osteoporosis. In this study, we investigated the effects of two types of CCB on bone metabolism: cilnidipine (L-/N-type CCB), which suppresses norepinephrine release from the sympathetic nerve, and amlodipine (L-type CCB). In ovariectomized female spontaneous hypertensive rats, administration of cilnidipine, but not amlodipine, resulted in a significant increase in the ratio of alkaline phosphatase to tartrate-resistant acid phosphatase (TRAP) and a decrease in the number of osteoclasts, as assessed by TRAP staining in the proximal tibia. Bone mineral density, moreover, was significantly higher in the cilnidipine group as compared with the amlodipine group and was associated with a significant decrease in a urinary collagen degradation product (deoxypyridinoline). The degree of prevention of osteoporosis by cilnidipine was similar to that of carvedilol (a b-blocker) because b-blockers reduce fracture risks though the inhibition of osteoclast activation. Interestingly, these effects cannot be attributed to the reduction of blood pressure because all three drugs significantly decreased blood pressure. In contrast, both cilnidipine and carvedilol, but not amlodipine, significantly decreased heart rate, indicating that both cilnidipine and carvedilol suppressed sympathetic nervous activity. Overall, our present data showed that cilnidipine (L-/N-type CCB) ameliorated osteoporosis in ovariectomized hypertensive rats. These pleiotropic effects of antihypertensive drugs such as cilnidipine and carvedilol might provide additional benefits in the treatment of hypertensive postmenopausal women.

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“…14,15 However, it has recently been reported that both a dual L-/N-type CCB cilnidipine and an L-/T-type CCB efonidipine exhibit a greater antiproteinuric effect than does amlodipine. 16,17 Benidipine, another dual L-/T-type CCB, dilates both efferent and afferent arterioles and reduces glomerular pressure. 18 Therefore, benidipine also may exert renoprotective effects.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the antiproteinuric effects of the calcium channel blockers benidipine and amlodipine administered in combination with angiotensin receptor blockers to hypertensive patients with stage 3–5 chronic kidney disease

et al. 2009

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Benidipine, an L-and T-type calcium channel blocker, dilates both efferent and afferent arterioles and reduces glomerular pressure. Thus, it may exert renoprotective effects. We conducted an open-labeled, randomized trial to compare the blood pressure (BP)-lowering effect and antiproteinuric effect of benidipine with those of amlodipine in hypertensive patients with moderate-to-advanced-stage chronic kidney disease (CKD) (stages 3-5). These patients were already being administered the current maximum recommended doses of angiotensin receptor blockers (ARBs). Patients with BP X140/90 mm Hg, despite treatment with the maximum recommended dose of ARBs, were randomly assigned to two groups. The patients received either of the following treatment regimens: 4 mg day À1 of benidipine, which was increased up to a dose of 16 mg day À1 (B group; n¼24), and 2.5 mg day À1 of amlodipine, which was increased up to a dose of 10 mg day À1 amlodipine (A group; n¼23). After 6 months of treatment, a significant and comparable reduction in the systolic and diastolic BP was seen in both groups. The decrease in the urinary protein to creatinine ratio in the B group was significantly lower than that in the A group. Benidipine exerted antiproteinuric effect to a greater extent than did amlodipine, even in patients with diabetic nephropathy. We conclude that the addition of benidipine, rather than amlodipine, ameliorates urinary protein excretion in hypertensive patients with CKD who are already being administered ARBs. Therefore, we propose a combination therapy with benidipine and ARBs, even for patients with moderate-to-advanced-stage CKD.

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Antiproteinuric effect of the calcium channel blocker cilnidipine added to renin-angiotensin inhibition in hypertensive patients with chronic renal disease

Cited by 132 publications

References 39 publications

Renoprotective and antioxidant effects of cilnidipine in hypertensive patients

Renoprotective and antioxidant effects of cilnidipine in hypertensive patients

Cilnidipine, but not amlodipine, ameliorates osteoporosis in ovariectomized hypertensive rats through inhibition of the N-type calcium channel

Comparison of the antiproteinuric effects of the calcium channel blockers benidipine and amlodipine administered in combination with angiotensin receptor blockers to hypertensive patients with stage 3–5 chronic kidney disease

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