T/L-type calcium channel blocker reduces the composite ranking of relative risk according to new KDIGO guidelines in patients with chronic kidney disease

BMC Nephrology

Masayoshi Soma²  Yoshinori Yoshida¹  Hiroko Suzuki¹  Kazuyoshi Okada¹  Masanori Abe¹ 

[1] Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan;Division of General Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan

关键词: T-type calcium channel;    Kidney Disease: Improving Global Outcomes (KDIGO);    Calcium channel blocker;    Benidipine;   

Others  :  1082904
DOI  :  10.1186/1471-2369-14-135

 received in 2012-08-01, accepted in 2013-06-04,  发布年份 2013

【 摘 要 】

Background

Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) group recommended that patients with chronic kidney disease (CKD) be assigned according to stage and composite relative risk on the basis of glomerular filtration rate (GFR) and albuminuria criteria. The aim of this post-hoc analysis was to investigate the effects of add-on therapy with calcium channel blockers (CCBs) on changes in the composite ranking of relative risk according to KDIGO guidelines. Benidipine, an L- and T-type CCB, and amlodipine, an L-type CCB to angiotensin II receptor blocker (ARB), were examined.

Methods

Patients with blood pressure (BP) > 130/80 mmHg, an estimated GFR (eGFR) of 30–90 mL/min/1.73 m², and albuminuria > 30 mg/gCr, despite treatment with the maximum recommended dose of ARB, were randomly assigned to two groups. Each group received one of two treatments: 2 mg benidipine daily, increased to 8 mg daily (n = 52), or 2.5 mg amlodipine daily, increased to 10 mg daily (n = 52).

Results

After 6 months of treatment, a significant and comparable reduction in systolic and diastolic BP was observed in both groups. The eGFR was significantly decreased in the amlodipine group, but there was no significant change in the benidipine group. The decrease in albuminuria in the benidipine group was significantly lower than in the amlodipine group. The composite ranking of relative risk according to the new KDIGO guidelines was significantly improved in the benidipine group; however, no significant change was noted in the amlodipine group. Moreover, significantly fewer cases in the benidipine group than the amlodipine group showed a reduced risk category score.

Conclusion

The present post-hoc analysis showed that compared to amlodipine benidipine results in a greater reduction in albuminuria accompanied by an improved composite ranking of relative risk according to the KDIGO CKD severity classification.

Trial registration

Trial registration Number: UMIN000002644

【 授权许可】

   
2013 Abe et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Levey AS, de Jong PE, Coresh J, Nahas ME, Astor BC, Matsushita K, Gansevoort RT, Kasiske BL, Eckardt KU: The definition, classification and prognosis of chronic kidney disease: a KDIGO Controversies Conference report. Kidney Int 2011, 80:17-28.
• [2]K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification Am J Kidney Dis 2002, 39:1-266.
• [3]Astor BC, Matsushita K, Gansevoort RT, van der Velde M, Woodward M, Levey AS, Jong PE, Coresh J, Astor BC, Matsushita K, Gansevoort RT, van der Velde M, Woodward M, Levey AS, de Jong PE, Coresh J, El-Nahas M, Eckardt KU, Kasiske BL, Wright J, Appel L, Greene T, Levin A, Djurdjev O, Wheeler DC, Landray MJ, Townend JN, Emberson J, Clark LE, Chronic Kidney Disease Prognosis Consortium, et al.: Lower estimated glomerular filtration rate and higher albuminuria are associated with mortality and end-stage renal disease. A collaborative meta-analysis of kidney disease population cohorts. Kidney Int 2011, 79:1341-1352.
• [4]Gansevoort RT, Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, de Jong PE, Coresh J, Chronic Kidney Disease Prognosis Consortium: Lower estimated glomerular filtration rate and higher albuminuria are associated with adverse kidney outcomes in both general and high-risk populations. A collaborative meta-analysis of general and high-risk population cohorts. Kidney Int 2011, 80:93-104.
• [5]Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, de Jong PE, Coresh J, Gansevoort RT: Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet 2010, 375:2073-2081.
• [6]Lewis EJ, Hunsicker LG, Bain RP, Rohde RD: The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Eng J Med 1993, 329:1456-1462.
• [7]Brenner BM, Cooper MD, De Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S: Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Eng J Med 2001, 345:861-869.
• [8]Japanese Society of Hypertension: Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2009. Hypertension Res 2009, 32:4-107.
• [9]Waeber B: Managing hypertension in high-risk patients: lessons and promises from the STRATHE and ADVANCE trials. J Hypertens 2006, 24:19-27.
• [10]Perez-Reyes E: Molecular physiology of low-voltage-activated T-type calcium channels. Physiol Rev 2003, 83:117-161.
• [11]Jones SW: Overview of voltage-dependent calcium channels. J Bioenerg Biomembr 1998, 30:299-312.
• [12]Hayashi K, Wakino S, Sugano N, Ozawa Y, Homma K, Saruta T: Ca2+ channel subtypes and pharmacology in the kidney. Circ Res 2007, 100:342-353.
• [13]Abe M, Okada K, Maruyama N, Matsumoto S, Maruyama T, Fujita T, Matsumoto K, Soma M: Benidipine reduces albuminuria and plasma aldosterone in mild-to-moderate stage chronic kidney disease with albuminuria. Hypertens Res 2011, 34:268-273.
• [14]Abe M, Okada K, Maruyama T, Maruyama N, Matsumoto K: 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. Hypertens Res 2009, 32:270-275.
• [15]Abe M, Okada K, Maruyama N, Matsumoto S, Maruyama T, Fujita T, Matsumoto K, Soma M: Comparison between the antiproteinuric effects of the calcium channel blockers benidipine and cilnidipine in combination with angiotensin receptor blockers in hypertensive patients with chronic kidney disease. Expert Opin Investig Drugs 2010, 19:1027-1037.
• [16]Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A, Collaborators developing the Japanese equation for estimated GFR: Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 2009, 53:982-92.
• [17]Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, McCullough PA, Kasiske BL, Kelepouris E, Klag MJ, Parfrey P, Pfeffer M, Raij L, Spinosa DJ, Wilson PW, American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention: Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation 2003, 108:2154-2169.
• [18]Ruggenenti P, Perna A, Remuzzi G: Retarding progression of chronic renal disease: the neglected issue of residual proteinuria. Kidney Int 2003, 63:2254-2261.
• [19]de Zeeuw D, Remuzzi G, Parving HH, Keane WF, Zhang Z, Shahinfar S, Snapinn S, Cooper ME, Mitch WE, Brenner BM: Albuminuria, a therapeutic target for cardiovascular protection in type 2 diabetic patients with nephropathy. Circulation 2004, 110:921-927.
• [20]Koltkamp FA, de Zeeuw D, de Graeff PA, Laverman GD, Berl T, Remuzzi G, Packham D, Lewis JB, Parving HH, Heerspink HJL: Albuminuria and blood pressure, independent targets for cardioprotective therapy in patients with diabetes and nephropathy: a post hoc analysis of the combined RENAAL and IDNT trials. Eur Heart J 2011, 32:1493-1499.
• [21]Evans M, Bain SC, Hogan S, Bilous RW: Irbesartan delays progression of nephropathy as measured by estimated glomerular filtration rate: post hoc analysis of the Irbesartan Diabetic Nephropathy Trial. Nephrol Dial Transplant 2012, 27:2255-2263.
• [22]Nakamura T, Sato E, Fujiwara N, Kawagoe Y, Ueda Y, Sugaya T, Yamagishi S, Yamada S, Koide H: Comparative effects of benidipine and amlodipine on proteinuria, urinary 8-OHdG, urinary L-FABP, and inflammatory and atherosclerosis markers in early-stage chronic kidney disease. Am J Med Sci 2010, 339:157-163.
• [23]Hayashi K, Ozawa Y, Fujiwara K, Wakino S, Kumagai H, Saruta T: Role of actions of calcium antagonists on efferent arterioles-with special references to glomerular hypertension. Am J Nephrol 2003, 23:229-244.
• [24]Nishigaki K, Inoue Y, Yamanouchi Y, Fukumoto Y, Yasuda S, Sueda S, Urata H, Shimokawa H, Minatoguchi S: Prognostic effects of calcium channel blockers in patients with vasospastic angina. Circ J 2010, 74:1943-1950.
• [25]Ito A, Fukumoto Y, Shimokawa H: Changing characteristics of patients with vasospastic angina in the era of new calcium channel blockers. J Cardiovasc Pharmacol 2004, 44:480-485.
• [26]Yao K, Nagashima K, Miki H: Pharmacological, pharmacokinetic, and clinical properties of benidipine hydrochloride, a nevel, long-acting calcium channel blocker. J Pharmacol Sci 2006, 100:243-261.
• [27]Moriyama T, Karasawa A: Cardiovascular effects of benidipine and amlodipine in isolated tissues and anesthetized dogs. Biol Pharm Bull 1994, 17:1468-1471.
• [28]Karasawa A, Kubo K, Shuto K, Oka T: Pharmacological actions of benidipine hydrochloride in several isolated smooth muscles and myocardium. Arzneimittel-forschung/Drug Res 1988, 38:1722-1730.
• [29]Shimada S, Nakajima Y, Yamamoto K, Sawada Y, Iga T: Comparative pharmacodynamics of eight calcium channel blocking agents in Japaneses essential hypertensive patients. Biol Pharm Bull 1996, 19:430-437.
• [30]Miwa Y, Masai H, Shimizu M: Differential effects of calcium channel blockers on vascular endothelial function in patients with coronary spastic angina. Circ J 2009, 73:713-717.
• [31]Makino H, Aoki M, Hashiya N, Yamasaki K, Shimizu H, Miwa K, Ogihara T, Morishita R: A calcium channel blocker, benidipine, improves forearm reactive hyperemia in patients with essential hypertension. Blood Press Suppl 2005, 1:39-44.
• [32]Kita T, Suzuki Y, Eto T, Kitamura K: Long-term anti-hypertensive therapy with benidipine improves arterial stiffness over blood pressure lowering. Hypertens Res 2005, 28:959-964.
• [33]Wang N, Minatoguchi S, Chen XH, Arai M, Uno Y, Lu C, Misao Y, Nagai H, Takemura G, Fujiwara H: Benidipine reduces myocardial infarct size involving reduction of hydroxyl radicals and production of protein kinase C-dependent nitric oxide in rabbits. J Cardiocasc Pharmacol 2004, 43:747-757.
• [34]Satchell SC, Tooke JE: What is the mechanism of microalbuminuria in diabetes: a role for the glomerular endothelium? Diabetologia 2008, 51:714-725.
• [35]Ito S: Cardiorenal connection in chronic kidney disease. Clin Exp Nephrol 2012, 16:8-16.
• [36]Stehouwr CD, Nauta JJ, Zeldenrust GC, Hackeng WH, Donker AJ, den Ottolander GJ: Urinary albumin excretion, cardiovascular disease, and endothelial dysfunction in non-insulin-dependent diabetes mellitus. Lancet 1992, 340:319-323.
• [37]Stehouwer CD, Smulders YM: Microalbuminuria and risk for cardiovascular disease: analysis of potential mechanisms. J Am Soc Nephrol 2006, 17:2106-2111.
• [38]Malik AR, Sultan S, Turner ST, Kullo IJ: Urinary albumin excretion is associated with impaired flow- and nitroglycerin-mediated brachial artery dilation in hypertensive adults. J Hum Hypertens 2007, 21:231-238.
• [39]Matsushita K, Mahmoodi BK, Woodward M, Emberson JR, Jafar TH, Jee SH, Polkinghorne KR, Shankar A, Smith DH, Tonelli M, Warnock DG, Wen CP, Coresh J, Gansevoort RT, Hemmelgarn BR, Levey AS: Comparison of risk prediction using the CKD-EPI equation and the MDRD study equation for estimated glomerular filtration rate. JAMA 2012, 307:1941-1951.
• [40]Horio M, Imai E, Yasuda Y, Watanabe T, Matsuo S: Performance of GFR equations in Japanese subjects. Clin Exp Nephrol 2012. Oct 19. [Epub ahead of print]
• [41]Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, van Lente F, Greene T, Coresh J: A new equation to estimate glomerular filtration rate. Ann Intern Med 2009, 150:604-612.
• [42]Horio M, Imai E, Yasuda Y, Watanabe T, Matsuo S: Modification of the CKD epidemiology collaboration (CKD-EPI) equation for Japanese: accuracy and use for population estimates. Am J Kidney Dis 2010, 56:32-38.
• [43]Nakayama M, Sato T, Miyazaki M, Matsushima M, Sato H, Taguma Y, Ito S: Incresed risk of cardiovascular events and mortality among non-diabetic chronic kidney disease patients with hypertensive nephropathy: the Gonryo study. Hypertens Res 2011, 34:1106-1110.
• [44]Bouchi R, Babazono T, Yoshida N, Nyumura I, Toya K, Hayashi T, Hanai K, Tanaka N, Ishii A, Iwamoto Y: Association of albuminuria and reduced estimated glomerular filtration rate with incident stroke and coronary artery disease in patients with type 2 diabetes. Hypertens Res 2010, 33:1298-1304.
• [45]Levey AS, Cattran D, Friedman A, Miller WG, Sedor J, Tuttle K, Kasiske B, Hostetter T: Proteinuria as a surrogate outcome in CKD: Report of a Scientific Workshop Sponsored by the National Kidney Foundation and the US Food and Drug Administration. Am J Kidney Dis 2009, 54:205-226.