Influence of T-calcium channel blocker treatment on deterioration of renal function in chronic kidney disease

Omae, Kiyotsugu; Ogawa, Tetsuya; Nitta, Kosaku

doi:10.1007/s00380-008-1125-y

Cited by 12 publications

(8 citation statements)

References 30 publications

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“…33,34 Our present observations therefore imply a distinct therapeutic applicability of Ca channel blockers in CKD. 31,35 Of note, the present study showed that in patients with proteinuria at baseline, eGFR was lower than in non-proteinuric patients throughout the study period (Figures 4a and b, bottom). These observations are compatible with previous reports showing that proteinuria per se constitutes a risk factor for the development of CKD.…”

Section: Discussionmentioning

confidence: 52%

“…16 By contrast, novel types of Ca channel blockers, including efonidipine and benidipine, which possess T-type Ca channel blocking activity, 27,28 confer a greater benefit on renal function. 23,[29][30][31] Of interest, efonidipine possesses renal protective action via efferent arteriolar dilation, [17][18][19][20] the inhibition of Rho kinase 32 and, possibly, the inhibition of aldosterone activity. 33,34 Our present observations therefore imply a distinct therapeutic applicability of Ca channel blockers in CKD.…”

Section: Discussionmentioning

confidence: 99%

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Impact of renal function on cardiovascular events in elderly hypertensive patients treated with efonidipine

et al. 2010

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on behalf of the JATOS Study GroupThis study evaluated the impact of renal function on cardiovascular outcomes in elderly hypertensive patients enrolled in the Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive patients. The patients were randomly assigned to either a strict-treatment group (target systolic blood pressure (BP) o140 mm Hg, n¼2212) or a mild-treatment group (target systolic BP, 140 to o160 mm Hg, n¼2206), each with efonidipine (a T/L-type Ca channel blocker)-based regimens. Cardiovascular events (stroke, cardiovascular disease and renal disease) were evaluated during the 2-year follow-up period following the prospective randomized open-blinded end-point method. Estimated glomerular filtration rate (eGFR) was elevated throughout the trial period in both the strict-treatment (59.4-62 ml min À1 per 1.73 m 2 ) and the mild-treatment group (58.8-61.4 ml min À1 per 1.73 m 2 ). This tendency was also observed in diabetic patients and patients aged X75 years, with baseline eGFRo60 ml min À1 per 1.73 m 2 . Baseline eGFR (o60 vs. X60 ml min À1 per 1.73 m 2 ) had no definite relationship with the incidence of cardiovascular events, nor did the level of BP control. Proteinuria at the time of entry into the study, however, was significantly correlated with cardiovascular event rates (7.1%), an association that was more apparent in patients with eGFRo60 ml min À1 per 1.73 m 2 (8.2%). Furthermore, the event rate was more elevated in patients with greater declines in eGFR and was amplified when the baseline eGFR was o60 ml min À1 per 1.73 m 2 . In conclusion, the rates of decline of renal function and proteinuria constitute critical risk factors for cardiovascular events in elderly hypertensive patients, trends that are enhanced when baseline eGFR is diminished. Furthermore, the fact that efonidipine-based regimens ameliorate renal function in elderly hypertensive patients with chronic kidney disease may offer novel information on the mechanisms of cardiovascular protection.

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Impact of renal function on cardiovascular events in elderly hypertensive patients treated with efonidipine

et al. 2010

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“…19,20) In fact, it has been reported that T/L-type CCBs dilate both renal afferent and efferent arterioles to decrease intraglomerular pressure in patients with nephritis or nephrosclerosis, 21) with better renal outcomes than those observed for L-type CCBs. 22) The present study compared the L-type CCB amlodipine and T/L-type CCB benidipine in CKD patients with albuminuria. In the amlodipine and benidipine groups in the overall study population, there was no significant improvement in UAE.…”

Section: Discussionmentioning

confidence: 99%

Improvements in Augmentation Index and Urinary Albumin Excretion With Benidipine in Hypertensive Patients With Chronic Kidney Disease

et al. 2016

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SummaryAlthough calcium channel blockers (CCB) are expected to improve the augmentation index (AI) in CKD patients, the potential effect of benidipine on AI has been poorly studied.The present study aimed to compare the effect of benidipine and amlodipine in the treatment of CKD patients as measured through AI and urinary albumin excretion (UAE). Eligible patients with CKD were randomized to either the benidipine group or amlodipine group. Changes in UAE and AI were compared with target blood pressure level set at < 130/80 mmHg. A total of 108 patients were enrolled; 88 patients who were followed up were included in the analysis. Although no significant change in renal function was noted in either group, there was a significant improvement in AI only in the benidipine group (85.7 ± 13.3% to 81.4 ± 15.2%; P = 0.021) A subgroup analysis of 64 patients who achieved SBP < 140 mmHg at the end of follow-up (31 on amlodipine and 33 on benidipine) was carried out. Significant improvement in AI was noted only in the benidipine group (84.5 ± 13.6% to 79.5 ± 15.2%; P = 0.0138). In another subgroup of patients with UAE ≥ 300 mg/g Cr, a significant improvement in UAE in the benidipine group was found compared with the amlodipine group (-25 ± 46, 51 ± 60%, P = 0.031, respectively).These results suggest that benidipine might reduce significantly AI and might have potentially greater improvements in UAE than amlodipine in advanced CKD patients receiving RAS inhibitors. (Int Heart J 2016; 57: 53-60)

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“…Furthermore, a prospective cohort study attempting a direct comparison of renal effects of T-type and L-type CCBs in non-diabetic CKD patients reveals more beneficial effects of T-type CCBs than L-type CCBs on renal endpoints [26]. …”

Section: Clinical Studies Using Various Ccbsmentioning

confidence: 99%

Renal Microcirculation and Calcium Channel Subtypes

Homma¹,

Hayashi²,

Yamaguchi³

et al. 2014

CHYR

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It has recently been reported that voltage-dependent Ca channel subtypes, e.g., L-, T-, N-, and P/Q-type, are expressed in renal arterioles and renal tubules, and the inhibition of these channels exerts various effects on renal microcirculation. For example, selective blockade of L-type Ca channels with nifedipine preferentially dilates the afferent arteriole and potentially induces glomerular hypertension. On the other hand, recently developed Ca channel blockers (CCBs) such as mibefradil and efonidipine block both T-type and L-type Ca channels and consequently dilate both afferent and efferent arterioles, leading to lowering of intraglomerular pressure. Interestingly, aldosterone has recently been recognized as a factor exacerbating renal diseases, and its secretion from adrenal gland is mediated by T-type Ca channels. Furthermore, T-type CCBs were shown to ameliorate renal dysfunction by suppressing inflammatory processes and renin secretion. On the basis of histological evaluations, N-type Ca channels are present in peripheral nerve terminals innervating both afferent and efferent arterioles. Further, it was suggested that N-type CCBs such as cilnidipine suppress renal arteriolar constriction induced by enhanced sympathetic nerve activity, thereby lowering intraglomerular pressure. Taken together, various Ca channel subtypes are present in the kidney and blockade of selective channels with distinct CCBs exerts diverse effects on renal microcirculation. Inhibition of T-type and N-type Ca channels with CCBs is anticipated to exert pleiotropic effects that would retard the progression of chronic kidney disease through modulation of renal hemodynamic and non-hemodynamic processes.

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Influence of T-calcium channel blocker treatment on deterioration of renal function in chronic kidney disease

Cited by 12 publications

References 30 publications

Impact of renal function on cardiovascular events in elderly hypertensive patients treated with efonidipine

Impact of renal function on cardiovascular events in elderly hypertensive patients treated with efonidipine

Improvements in Augmentation Index and Urinary Albumin Excretion With Benidipine in Hypertensive Patients With Chronic Kidney Disease

Renal Microcirculation and Calcium Channel Subtypes

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