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Clinical and Experimental Nephrology
Published in: Clinical and Experimental Nephrology 3/2022

Open Access 01-03-2022 | Albuminuria | Review article

Calcium channel blocker in patients with chronic kidney disease

Authors: Shoko Ohno, Akira Ishii, Motoko Yanagita, Hideki Yokoi

Published in: Clinical and Experimental Nephrology | Issue 3/2022

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Abstract

Background

Chronic kidney disease (CKD) is involved in a progressive deterioration in renal function over the years and is now a global public health problem. Currently, reducing the number of patients progressing to end-stage renal failure is urgently necessary. Hypertension and CKD interact with each other, and good control of blood pressure (BP) can improve CKD patients’ prognosis. With the current global trend for more strict BP control, the importance of BP management and the need for medication to achieve this strict goal are increasing. Calcium channel blockers (CCBs), which target voltage-dependent calcium channels, are frequently used in combination with renin–angiotensin–aldosterone system inhibitors for CKD patients because of their strong BP-lowering properties and relatively few adverse side effects. Calcium channels have several subtypes, including L, N, T, P/Q, and R, and three types of CCBs, L-type CCBs, L-/T-type CCBs, and L-/N-type CCBs, that are available. Nowadays, the new functions and effects of the CCBs are being elucidated.

Conclusion

We should use different types of CCBs properly depending on their pharmacological effects, such as the strength of antihypertensive effects and the organ protection effects, taking into account the pathophysiology of the patients. In this article, the role and the use of CCBs in CKD patients are reviewed.
Literature
1.
Levey AS, et al. Chronic kidney disease as a global public health problem: approaches and initiatives—a position statement from Kidney Disease Improving Global Outcomes. Kidney Int. 2007;72(3):247–59.PubMed
2.
Whaley-Connell AT, et al. CKD in the United States: Kidney Early Evaluation Program (KEEP) and National Health and Nutrition Examination Survey (NHANES) 1999–2004. Am J Kidney Dis. 2008;51(4 Suppl 2):S13-20.PubMed
3.
Bakris GL, et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis. 2000;36(3):646–61.PubMed
4.
Jafar TH, et al. Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition: a patient-level meta-analysis. Ann Intern Med. 2003;139(4):244–52.PubMed
5.
Afkarian M, et al. Clinical manifestations of kidney disease among US adults with diabetes, 1988–2014. JAMA. 2016;316(6):602–10.PubMedPubMedCentral
6.
Vejakama P, et al. Reno-protective effects of renin-angiotensin system blockade in type 2 diabetic patients: a systematic review and network meta-analysis. Diabetologia. 2012;55(3):566–78.PubMed
7.
8.
Ertel EA, et al. Nomenclature of voltage-gated calcium channels. Neuron. 2000;25(3):533–5.PubMed
9.
Catterall WA. Structure and regulation of voltage-gated Ca2+ channels. Annu Rev Cell Dev Biol. 2000;16:521–55.PubMed
10.
Tamargo J, Ruilope LM. Investigational calcium channel blockers for the treatment of hypertension. Expert Opin Investig Drugs. 2016;25(11):1295–309.PubMed
11.
Cheung AK, Chang TI, Cushman WC, Furth SL, Hou FF, Ix JH, Knoll GA, Muntner P, Pecoits-Filho R, Sarnak MJ, Tobe SW, Tomson CRV, Mann JFE. Kidney disease: improving global outcomes blood pressure work G. KDIGO 2021 clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int. 2021;99(3S):S1–87.
12.
Unger T, et al. 2020 International society of hypertension global hypertension practice guidelines. Hypertension. 2020;75(6):1334–57.PubMed
13.
SPRINT Research Group, Wright JT Jr, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373(22):2103–16.
14.
Umemura S, et al. The Japanese society of hypertension guidelines for the management of hypertension (JSH 2019). Hypertens Res. 2019;42(9):1235–481.PubMed
15.
Hiragi S, et al. Association between the size of healthcare facilities and the intensity of hypertension therapy: a cross-sectional comparison of prescription data from insurance claims data. Hypertens Res. 2021;44(3):337–47.PubMed
16.
Xie X, et al. Renin-angiotensin system inhibitors and kidney and cardiovascular outcomes in patients with CKD: a bayesian network meta-analysis of randomized clinical trials. Am J Kidney Dis. 2016;67(5):728–41.PubMed
17.
18.
ONTARGET Investigators O, Yusuf S, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358(15):1547–59.
19.
Fried LF, et al. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med. 2013;369(20):1892–903.PubMed
20.
Bakris GL, Agarwal R, Anker SD, Pitt B, Ruilope LM, Rossing P, et al. Effect of finerenone on chronic kidney disease outcomes in Type 2 diabetes. N Engl J Med. 2020;383(23):2219–29.PubMed
21.
Moreno DH. Molecular and functional diversity of voltage-gated calcium channels. Ann NY Acad Sci. 1999;868:102–17.
22.
Hofmann F, Biel M, Flockerzi V. Molecular basis for Ca2+ channel diversity. Annu Rev Neurosci. 1994;17:399–418.PubMed
23.
Hayashi K, et al. Ca2+ channel subtypes and pharmacology in the kidney. Circ Res. 2007;100(3):342–53.PubMed
24.
25.
Zhao PL, et al. Tubular and cellular localization of the cardiac L-type calcium channel in rat kidney. Kidney Int. 2002;61(4):1393–406.PubMed
26.
Andreasen D, et al. The α1G-subunit of a voltage-dependent Ca2+ channel is localized in rat distal nephron and collecting duct. Am J Physiol Renal Physiol. 2000;279(6):F997-1005.PubMed
27.
Poulsen CB, et al. T-type voltage-gated calcium channels regulate the tone of mouse efferent arterioles. Kidney Int. 2011;79(4):443–51.PubMed
28.
Hansen PB, et al. Functional importance of L- and P/Q-type voltage-gated calcium channels in human renal vasculature. Hypertension. 2011;58(3):464–70.PubMed
29.
Hansen PB. New role of P/Q-type voltage-gated calcium channels: from transmitter release to contraction of renal vasculature. J Cardiovasc Pharmacol. 2015;65(5):406–11.PubMed
30.
Fan YY, et al. Cilnidipine suppresses podocyte injury and proteinuria in metabolic syndrome rats: possible involvement of N-type calcium channel in podocyte. J Hypertens. 2010;28(5):1034–43.PubMedPubMedCentral
31.
Ohno S, et al. Ablation of the N-type calcium channel ameliorates diabetic nephropathy with improved glycemic control and reduced blood pressure. Sci Rep. 2016;6:27192.PubMedPubMedCentral
32.
Hayashi K, et al. Disparate effects of calcium antagonists on renal microcirculation. Hypertens Res. 1996;19(1):31–6.PubMed
33.
Ohishi M, et al. Renal-protective effect of T-and L-type calcium channel blockers in hypertensive patients: an Amlodipine-to-Benidipine Changeover (ABC) study. Hypertens Res. 2007;30(9):797–806.PubMed
34.
Yamamoto E, et al. Benidipine, a dihydropyridine L-type/T-type calcium channel blocker, affords additive benefits for prevention of cardiorenal injury in hypertensive rats. J Hypertens. 2010;28(6):1321–9.PubMed
35.
Thuesen AD, et al. Deficiency of T-type Ca2+ channels Cav3.1 and Cav3.2 has no effect on angiotensin II-induced hypertension but differential effect on plasma aldosterone in mice. Am J Physiol Renal Physiol. 2019;317(2):F254–63.PubMed
36.
Mori Y, et al. Ca2+ channel alpha1B subunit (CaV 2.2) knockout mouse reveals a predominant role of N-type channels in the sympathetic regulation of the circulatory system. Trends Cardiovasc Med. 2002;12(6):270–5.PubMed
37.
Marin R, et al. Systemic and glomerular hypertension and progression of chronic renal disease: the dilemma of nephrosclerosis. Kidney Int Suppl. 2005;99:S52–6.
38.
Wang T, Takabatake T. Effects of vasopeptidase inhibition on renal function and tubuloglomerular feedback in spontaneously hypertensive rats. Hypertens Res. 2005;28(7):611–8.PubMed
39.
Hansen PB, et al. Differential expression of T- and L-type voltage-dependent calcium channels in renal resistance vessels. Circ Res. 2001;89(7):630–8.PubMed
40.
Hansen PB, Jensen BL, Andreasen D, Friis UG, Skott O. Vascular smooth muscle cells express the α1A subunit of a P-/Q-type voltage-dependent Ca2+ Channel, and It is functionally important in renal afferent arterioles. Circ Res. 2000;87(10):896–902.PubMed
41.
Lei B, Nakano D, Fujisawa Y, Liu Y, Hitomi H, Kobori H, et al. N-type calcium channel inhibition with cilnidipine elicits glomerular podocyte protection independent of sympathetic nerve inhibition. J Pharmacol Sci. 2012;119(4):359–67.PubMedPubMedCentral
42.
Konda T, et al. Effects of L/N-type calcium channel antagonist, cilnidipine on progressive renal injuries in Dahl salt-sensitive rats. Biol Pharm Bull. 2006;29(5):933–7.PubMed
43.
Abe M, Soma M. Multifunctional L/N- and L/T-type calcium channel blockers for kidney protection. Hypertens Res. 2015;38(12):804–6.PubMed
44.
Sugano N, et al. Mechanistic view of renal protective action of calcium channel blockade. Curr Hypertens Rev. 2013;9(3):187–92.PubMed
45.
Abe M, et al. Benidipine reduces albuminuria and plasma aldosterone in mild-to-moderate stage chronic kidney disease with albuminuria. Hypertens Res. 2011;34(2):268–73.PubMed
46.
Li X, Yang MS. Effects of T-type calcium channel blockers on renal function and aldosterone in patients with hypertension: a systematic review and meta-analysis. PLoS ONE. 2014;9(10): e109834.PubMedPubMedCentral
47.
Tani S, et al. Effects of the T/L-type calcium channel blocker benidipine on albuminuria and plasma aldosterone concentration. A pilot study involving switching from L-type calcium channel blockers to benidipine. Int Heart J. 2014;55(6):519–25.PubMed
48.
Hayashi K, et al. Impact of renal function on cardiovascular events in elderly hypertensive patients treated with efonidipine. Hypertens Res. 2010;33(11):1211–20.PubMed
49.
Konoshita T, et al. 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. J Hypertens. 2010;28(10):2156–60.PubMed
50.
Fujita T, et al. Antiproteinuric effect of the calcium channel blocker cilnidipine added to renin-angiotensin inhibition in hypertensive patients with chronic renal disease. Kidney Int. 2007;72(12):1543–9.PubMed
51.
Brunette MG, et al. Characterization of three types of calcium channel in the luminal membrane of the distal nephron. Can J Physiol Pharmacol. 2004;82(1):30–7.PubMed
52.
Sugano N, et al. T-type calcium channel blockade as a therapeutic strategy against renal injury in rats with subtotal nephrectomy. Kidney Int. 2008;73(7):826–34.PubMed
53.
Baylis C, Qiu C, Engels K. Comparison of L-type and mixed L- and T-type calcium channel blockers on kidney injury caused by deoxycorticosterone-salt hypertension in rats. Am J Kidney Dis. 2001;38(6):1292–7.PubMed
54.
Ino M, et al. Functional disorders of the sympathetic nervous system in mice lacking the α1B subunit (Cav 22) of N-type calcium channels. Proc Natl Acad Sci USA. 2001;98(9):5323–8.PubMedPubMedCentral
55.
Yamada Y, et al. Inhibition of N-type Ca2+ channels ameliorates an imbalance in cardiac autonomic nerve activity and prevents lethal arrhythmias in mice with heart failure. Cardiovasc Res. 2014;104(1):183–93.PubMed
56.
Mishima K, et al. Attenuation of renal fibrosis after unilateral ureteral obstruction in mice lacking the N-type calcium channel. PLoS ONE. 2019;14(10): e0223496.PubMedPubMedCentral
57.
Messerli FH. Vasodilatory edema: a common side effect of antihypertensive therapy. Curr Cardiol Rep. 2002;4(6):479–82.PubMed
58.
Messerli FH, Grossman E. Pedal edema–not all dihydropyridine calcium antagonists are created equal. Am J Hypertens. 2002;15(11):1019–20.PubMed
59.
Jamerson K, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 2008;359(23):2417–28.PubMed
60.
Imagawa K, et al. Inhibitory effect of efonidipine on aldosterone synthesis and secretion in human adrenocarcinoma (H295R) cells. J Cardiovasc Pharmacol. 2006;47(1):133–8.PubMed
61.
Hirning LD, et al. Dominant role of N-type Ca2+ channels in evoked release of norepinephrine from sympathetic neurons. Science (New York, NY). 1988;239(4835):57–61.
62.
Takahara A, et al. Cilnidipine attenuates renal nerve stimulation-induced renal vasoconstriction and antinatriuresis in anesthetized dogs. Jpn J Pharmacol. 1997;75(1):27–32.PubMed
63.
Konda T, et al. The N- and L-type calcium channel blocker cilnidipine suppresses renal injury in Dahl rats fed a high-sucrose diet, an experimental model of metabolic syndrome. Nephron Physiol. 2005;101(1):p1-13.PubMed
64.
Konda T, et al. Different effects of L/N-type and L-type calcium channel blockers on the renin-angiotensin-aldosterone system in SHR/Izm. Am J Nephrol. 2009;30(2):155–61.PubMed
Metadata
Title
Calcium channel blocker in patients with chronic kidney disease
Authors
Shoko Ohno
Akira Ishii
Motoko Yanagita
Hideki Yokoi
Publication date
01-03-2022
Publisher
Springer Singapore
Published in
Clinical and Experimental Nephrology / Issue 3/2022
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-021-02153-1

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