Renoprotective effect of N-type Ca channel blockade in diabetic nephropathy

Fujisawa, Tomomi; Ikegami, Hiroshi; Noso, Shinsuke; Hiromine, Yoshihisa; Kawabata, Yumiko; Nishino, Masanori; Asano, Kazuaki; Ogihara, Toshio

doi:10.1016/j.jdiacomp.2006.06.001

Cited by 16 publications

(15 citation statements)

References 26 publications

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“…Add-on effect of cilnidipine on albuminuria reduction was demonstrated for the first time in about 40 diabetic cases in each group on the top of an angiotensin receptor blocker (ARB), valsartan [26]. Compared with amlodipine, albuminuria reduction was obtained by cilnidipine on the top of renin-angiotensin inhibition in 38 diabetic patients in a cross-over fashion [27]. As the first multicenter large-scale trial, compared with amlodipine, antiproteinuric effect of cilnidipine in CKD patients with overt proteinuria was demonstrated on the top of renin-angiotensin inhibition (147 cases in cilnidipine group and 130 cases in amlodipine group) in CARTER study [28].…”

Section: Discussionmentioning

confidence: 99%

A new-generation N/L-type calcium channel blocker leads to less activation of the renin–angiotensin system compared with conventional L type calcium channel blocker

Konoshita

Makino

Kimura

et al. 2010

Journal of Hypertension

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Section: Discussionmentioning

confidence: 99%

A new-generation N/L-type calcium channel blocker leads to less activation of the renin–angiotensin system compared with conventional L type calcium channel blocker

Konoshita

Makino

Kimura

et al. 2010

Journal of Hypertension

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“…A small-sized ( n = 28), short-duration (3 months) study 32 showed that switching from amlodipine to cilnidipine decreased urinary albumin levels in patients with DN and microalbuminuria. Another small-sized ( n = 35) crossover study 33 suggested the cilnidipine was superior to amlodipine for the treatment of hypertensive patients with type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Antialbuminuric Effects of L-/N-type and L-type Calcium Channel Blockers in Hypertensive Patients with Diabetes and Microalbuminuria: The Study of Assessment for Kidney Function by Urinary Microalbumin in Randomized (SAKURA) Trial

Ando¹,

Ueshima²,

Tanaka³

et al. 2013

Int. J. Med. Sci.

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Objective: To clarify whether the L-/N-type calcium channel blocker (CCB) cilnidipine is more renoprotective than the L-type CCB amlodipine in patients with early-stage diabetic nephropathy.Methods: In this prospective, multicenter, open-labeled, randomized trial, the antialbuminuric effects of cilnidipine and amlodipine were examined in renin-angiotensin system (RAS) inhibitor-treated patients with hypertension (blood pressure [BP]: 130-180/80-110 mmHg), type 2 diabetes, and microalbuminuria (urinary albumin to creatinine [Cr] ratio [UACR]: 30-300 mg/g).Results: Patients received cilnidipine (n = 179, final dose: 10.27 ± 4.13 mg/day) or amlodipine (n = 186, 4.87 ± 2.08 mg/day) for 12 months. Cilnidipine and amlodipine equally decreased BP. The UACR values for the cilnidipine and amlodipine groups were 111.50 ± 138.97 and 88.29 ± 63.45 mg/g, respectively, before treatment and 107.93 ± 130.23 and 89.07 ± 97.55 mg/g, respectively, after treatment. The groups showed similar changes for the natural logarithm of the UACR, serum Cr, and estimated glomerular filtration rate.Conclusions: Cilnidipine did not offer greater renoprotection than amlodipine in RAS inhibitor-treated hypertensive patients with type 2 diabetes and microalbuminuria.

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“…22 In small-sized clinical studies, cilnidipine had greater renoprotective effects than amlodipine. [23][24][25] Furthermore, it has been shown that cilnidipine was more beneficial than amlodipine as additional medication for hypertensive patients who had kidney disease associated with significant proteinuria and who were already under treatment with a renin-angiotensin system inhibitor. 26 The deoxycorticosterone acetate (DOCA)-salt rat is a useful model for the investigation of renal injury in the hypertensive setting.…”

Section: Introductionmentioning

confidence: 99%

L/N-type calcium channel blocker cilnidipine ameliorates proteinuria and inhibits the renal renin–angiotensin–aldosterone system in deoxycorticosterone acetate-salt hypertensive rats

et al. 2011

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Cilnidipine, an N/L-type calcium channel blocker, has been reported to inhibit sympathetic nerve activity and has a greater renoprotective effect than L-type calcium channel blockers. To investigate the hypothesis that cilnidipine might ameliorate advanced hypertensive nephropathy and inhibit the renal renin-angiotensin-aldosterone system, cilnidipine (1 mg per kg per day) or amlodipine (1 mg per kg per day) was administered to uninephrectomized deoxycorticosterone (DOCA)-salt hypertensive rats (DOCA-salt) for 4 weeks by gavage. Although the blood pressure in the DOCA-salt group was higher than that of control, neither cilnidipine nor amlodipine had any effect on the increase in blood pressure in the DOCA-salt group. The DOCA (40 mg per kg per week, subcutaneously (s.c.)) and salt (1% NaCl in drinking water) treatment significantly aggravated the levels of urinary protein excretion and creatinine clearance and increased glomerulosclerosis and collagen deposition in the tubulointerstitial area of the kidney. These effects were attenuated by cilnidipine treatment. Reverse transcription-polymerase chain reaction analysis revealed that the renal expression of mRNA for collagen I/IV and transforming growth factor-b was enhanced in the DOCA-salt group and that the overexpression of these molecules was suppressed by cilnidipine. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived superoxide production in the kidney and urinary norepinephrine excretion, which were enhanced in the DOCA-salt group, were suppressed by cilnidipine. Cilnidipine also decreased the activity and expression of angiotensin-converting enzyme (ACE) and the aldosterone concentration in the renal homogenate. Although neither cilnidipine nor amlodipine had any effect on the increased blood pressure in the DOCA-salt group, these renal changes were not induced by treatment with amlodipine. In conclusion, cilnidipine inhibited renal dysfunction, sympathetic nerve activity and renal renin-angiotensin-aldosterone system in the DOCA-salt group.

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Renoprotective effect of N-type Ca channel blockade in diabetic nephropathy

Cited by 16 publications

References 26 publications

A new-generation N/L-type calcium channel blocker leads to less activation of the renin–angiotensin system compared with conventional L type calcium channel blocker

A new-generation N/L-type calcium channel blocker leads to less activation of the renin–angiotensin system compared with conventional L type calcium channel blocker

Comparison of the Antialbuminuric Effects of L-/N-type and L-type Calcium Channel Blockers in Hypertensive Patients with Diabetes and Microalbuminuria: The Study of Assessment for Kidney Function by Urinary Microalbumin in Randomized (SAKURA) Trial

L/N-type calcium channel blocker cilnidipine ameliorates proteinuria and inhibits the renal renin–angiotensin–aldosterone system in deoxycorticosterone acetate-salt hypertensive rats

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