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Published in: Clinical and Experimental Nephrology 2/2013

01-04-2013 | Original Article

The administration of pitavastatin augments creatinine clearance associated with reduction in oxidative stress parameters: acute and early effects

Authors: Hirokazu Kakuda, Keizo Kanasaki, Daisuke Koya, Noboru Takekoshi

Published in: Clinical and Experimental Nephrology | Issue 2/2013

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Abstract

Background

Chronic kidney disease (CKD) is a serious health problem worldwide. Therapies that can halt the progression of CKD are limited, and the identification of new strategies for CKD treatment is therefore important. Pitavastatin, one of the newest statins introduced to the market, has been shown to exhibit some beneficial effects on renal and endothelial function.

Method

We enrolled 12 healthy volunteers for our study. With or without pitavastatin administration, creatinine clearance (Ccr), urinary albumin excretion, lipid status, and oxidative stress markers were evaluated in acute and early phases after administration of the drug.

Results

A single pitavastatin administration increased Ccr and reduced oxidative stress parameters, such as 8-OHdG levels and isoprostane production, within 6 h, without altering lipid status in healthy participants. A two-week treatment with pitavastatin lowered total and LDL cholesterol and triglycerides but not HDL cholesterol at 7 and 14 days. This change in lipid profile is associated with enhanced Ccr and the suppression of oxidative stress parameters. Urinary albumin excretion was reduced after either acute or chronic administration of pitavastatin, although this effect was not yet significant.

Conclusion

We found that pitavastatin augmented Ccr and reduced oxidative stress parameters in healthy subjects. These data suggest that pitavastatin affects renal outcomes in both lipid status-dependent and -independent manners. These observations suggest that pitavastatin treatment could be beneficial for CKD patients.
Literature
1.
go back to reference Parker TF 3rd, Blantz R, Hostetter T, Himmelfarb J, Kliger A, Lazarus M, et al. The chronic kidney disease initiative. J Am Soc Nephrol. 2004;15(3):708–16.PubMedCrossRef Parker TF 3rd, Blantz R, Hostetter T, Himmelfarb J, Kliger A, Lazarus M, et al. The chronic kidney disease initiative. J Am Soc Nephrol. 2004;15(3):708–16.PubMedCrossRef
2.
go back to reference Makino H, Yasuda Y, Matsuo S. Challenges to chronic kidney disease in Japan: Japan Association of Chronic Kidney Disease Initiative (J-CKDI). Nihon Jinzo Gakkai Shi. 2006;48(8):711–3.PubMed Makino H, Yasuda Y, Matsuo S. Challenges to chronic kidney disease in Japan: Japan Association of Chronic Kidney Disease Initiative (J-CKDI). Nihon Jinzo Gakkai Shi. 2006;48(8):711–3.PubMed
3.
go back to reference Heart-Protection-Study-Collaborative-Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002360(9326):7–22. Heart-Protection-Study-Collaborative-Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002360(9326):7–22.
4.
go back to reference Tonelli M, Keech A, Shepherd J, Sacks F, Tonkin A, Packard C, et al. Effect of pravastatin in people with diabetes and chronic kidney disease. J Am Soc Nephrol. 2005;16(12):3748–54.PubMedCrossRef Tonelli M, Keech A, Shepherd J, Sacks F, Tonkin A, Packard C, et al. Effect of pravastatin in people with diabetes and chronic kidney disease. J Am Soc Nephrol. 2005;16(12):3748–54.PubMedCrossRef
5.
go back to reference Shepherd J, Kastelein JJ, Bittner V, Deedwania P, Breazna A, Dobson S, et al. Effect of intensive lipid lowering with atorvastatin on renal function in patients with coronary heart disease: the Treating to New Targets (TNT) study. Clin J Am Soc Nephrol. 2007;2(6):1131–9.PubMedCrossRef Shepherd J, Kastelein JJ, Bittner V, Deedwania P, Breazna A, Dobson S, et al. Effect of intensive lipid lowering with atorvastatin on renal function in patients with coronary heart disease: the Treating to New Targets (TNT) study. Clin J Am Soc Nephrol. 2007;2(6):1131–9.PubMedCrossRef
6.
go back to reference Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, et al. Effects of atorvastatin on kidney outcomes and cardiovascular disease in patients with diabetes: an analysis from the Collaborative Atorvastatin Diabetes Study (CARDS). Am J Kidney Dis Off J Nat Kidney Found. 2009;54(5):810–9.CrossRef Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, et al. Effects of atorvastatin on kidney outcomes and cardiovascular disease in patients with diabetes: an analysis from the Collaborative Atorvastatin Diabetes Study (CARDS). Am J Kidney Dis Off J Nat Kidney Found. 2009;54(5):810–9.CrossRef
7.
go back to reference Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011;377(9784):2181–92.PubMedCrossRef Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011;377(9784):2181–92.PubMedCrossRef
8.
go back to reference Nicholls SJ, Ballantyne CM, Barter PJ, Chapman MJ, Erbel RM, Libby P, et al. Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med. 2011;365(22):2078–87.PubMedCrossRef Nicholls SJ, Ballantyne CM, Barter PJ, Chapman MJ, Erbel RM, Libby P, et al. Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med. 2011;365(22):2078–87.PubMedCrossRef
10.
go back to reference Ludman A, Venugopal V, Yellon DM, Hausenloy DJ. Statins and cardioprotection—more than just lipid lowering? Pharmacol Ther. 2009;122(1):30–43.PubMedCrossRef Ludman A, Venugopal V, Yellon DM, Hausenloy DJ. Statins and cardioprotection—more than just lipid lowering? Pharmacol Ther. 2009;122(1):30–43.PubMedCrossRef
11.
go back to reference Romayne Kurukulasuriya L, Athappan G, Saab G, Whaley Connell A, Sowers JR. HMG CoA reductase inhibitors and renoprotection: the weight of the evidence. Ther Adv Cardiovasc Dis. 2007;1(1):49–59.PubMedCrossRef Romayne Kurukulasuriya L, Athappan G, Saab G, Whaley Connell A, Sowers JR. HMG CoA reductase inhibitors and renoprotection: the weight of the evidence. Ther Adv Cardiovasc Dis. 2007;1(1):49–59.PubMedCrossRef
12.
go back to reference da Silva PM. Are all statins the same? Focus on the efficacy and tolerability of pitavastatin. Am J Cardiovasc Drugs. 2011;11(2):93–107.PubMedCrossRef da Silva PM. Are all statins the same? Focus on the efficacy and tolerability of pitavastatin. Am J Cardiovasc Drugs. 2011;11(2):93–107.PubMedCrossRef
13.
go back to reference Douglas K, O’Malley PG, Jackson JL. Meta-analysis: the effect of statins on albuminuria. Ann Intern Med. 2006;145(2):117–24.PubMedCrossRef Douglas K, O’Malley PG, Jackson JL. Meta-analysis: the effect of statins on albuminuria. Ann Intern Med. 2006;145(2):117–24.PubMedCrossRef
14.
go back to reference Mann JF, Schmieder RE, McQueen M, Dyal L, Schumacher H, Pogue J, et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet. 2008;372(9638):547–53.PubMedCrossRef Mann JF, Schmieder RE, McQueen M, Dyal L, Schumacher H, Pogue J, et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet. 2008;372(9638):547–53.PubMedCrossRef
15.
go back to reference Imai E, Chan JC, Ito S, Yamasaki T, Kobayashi F, Haneda M, et al. Effects of olmesartan on renal and cardiovascular outcomes in type 2 diabetes with overt nephropathy: a multicentre, randomised, placebo-controlled study. Diabetologia. 2011;54(12):2978–86.PubMedCrossRef Imai E, Chan JC, Ito S, Yamasaki T, Kobayashi F, Haneda M, et al. Effects of olmesartan on renal and cardiovascular outcomes in type 2 diabetes with overt nephropathy: a multicentre, randomised, placebo-controlled study. Diabetologia. 2011;54(12):2978–86.PubMedCrossRef
16.
17.
go back to reference Kojima J, Fujino H, Abe H, Yosimura M, Kanda H, Kimata H. Identification of metabolites of NK-104, an HMG-CoA reductase inhibitor, in rat, rabbit and dog bile. Biol Pharm Bull. 1999;22(2):142–50.PubMedCrossRef Kojima J, Fujino H, Abe H, Yosimura M, Kanda H, Kimata H. Identification of metabolites of NK-104, an HMG-CoA reductase inhibitor, in rat, rabbit and dog bile. Biol Pharm Bull. 1999;22(2):142–50.PubMedCrossRef
18.
go back to reference Sakaeda T, Fujino H, Komoto C, Kakumoto M, Jin JS, Iwaki K, et al. Effects of acid and lactone forms of eight HMG-CoA reductase inhibitors on CYP-mediated metabolism and MDR1-mediated transport. Pharm Res. 2006;23(3):506–12.PubMedCrossRef Sakaeda T, Fujino H, Komoto C, Kakumoto M, Jin JS, Iwaki K, et al. Effects of acid and lactone forms of eight HMG-CoA reductase inhibitors on CYP-mediated metabolism and MDR1-mediated transport. Pharm Res. 2006;23(3):506–12.PubMedCrossRef
19.
go back to reference Arao K, Yasu T, Umemoto T, Jinbo S, Ikeda N, Ueda S, et al. Effects of pitavastatin on fasting and postprandial endothelial function and blood rheology in patients with stable coronary artery disease. Circ J. 2009;73(8):1523–30.PubMedCrossRef Arao K, Yasu T, Umemoto T, Jinbo S, Ikeda N, Ueda S, et al. Effects of pitavastatin on fasting and postprandial endothelial function and blood rheology in patients with stable coronary artery disease. Circ J. 2009;73(8):1523–30.PubMedCrossRef
20.
go back to reference Sakabe K, Fukuda N, Fukuda Y, Wakayama K, Nada T, Morishita S, et al. Comparisons of short- and intermediate-term effects of pitavastatin versus atorvastatin on lipid profiles, fibrinolytic parameter, and endothelial function. Int J Cardiol. 2008;125(1):136–8.PubMedCrossRef Sakabe K, Fukuda N, Fukuda Y, Wakayama K, Nada T, Morishita S, et al. Comparisons of short- and intermediate-term effects of pitavastatin versus atorvastatin on lipid profiles, fibrinolytic parameter, and endothelial function. Int J Cardiol. 2008;125(1):136–8.PubMedCrossRef
21.
go back to reference Yoshida O, Kondo T, Kureishi-Bando Y, Sugiura T, Maeda K, Okumura K, et al. Pitavastatin, an HMG-CoA reductase inhibitor, ameliorates endothelial function in chronic smokers. Circ J. 2010;74(1):195–202.PubMedCrossRef Yoshida O, Kondo T, Kureishi-Bando Y, Sugiura T, Maeda K, Okumura K, et al. Pitavastatin, an HMG-CoA reductase inhibitor, ameliorates endothelial function in chronic smokers. Circ J. 2010;74(1):195–202.PubMedCrossRef
22.
go back to reference Sadowitz B, Maier KG, Gahtan V. Basic science review: statin therapy—Part I: the pleiotropic effects of statins in cardiovascular disease. Vasc Endovasc Surg. 2010;44(4):241–51.CrossRef Sadowitz B, Maier KG, Gahtan V. Basic science review: statin therapy—Part I: the pleiotropic effects of statins in cardiovascular disease. Vasc Endovasc Surg. 2010;44(4):241–51.CrossRef
23.
go back to reference Bech JN, Nielsen CB, Pedersen EB. Effects of systemic NO synthesis inhibition on RPF, GFR, UNa, and vasoactive hormones in healthy humans. Am J Physiol. 1996;270(5 Pt 2):F845–51.PubMed Bech JN, Nielsen CB, Pedersen EB. Effects of systemic NO synthesis inhibition on RPF, GFR, UNa, and vasoactive hormones in healthy humans. Am J Physiol. 1996;270(5 Pt 2):F845–51.PubMed
25.
go back to reference Righetti M, Sessa A. Cigarette smoking and kidney involvement. J Nephrol. 2001;14(1):3–6.PubMed Righetti M, Sessa A. Cigarette smoking and kidney involvement. J Nephrol. 2001;14(1):3–6.PubMed
26.
go back to reference Dobrian AD. ADMA and NOS regulation in chronic renal disease: beyond the old rivalry for l-arginine. Kidney Int. 2012;81(8):722–4.PubMedCrossRef Dobrian AD. ADMA and NOS regulation in chronic renal disease: beyond the old rivalry for l-arginine. Kidney Int. 2012;81(8):722–4.PubMedCrossRef
27.
go back to reference Kajimoto H, Kai H, Aoki H, Yasuoka S, Anegawa T, Aoki Y, et al. Inhibition of eNOS phosphorylation mediates endothelial dysfunction in renal failure: new effect of asymmetric dimethylarginine. Kidney Int. 2012;81(8):762–8.PubMedCrossRef Kajimoto H, Kai H, Aoki H, Yasuoka S, Anegawa T, Aoki Y, et al. Inhibition of eNOS phosphorylation mediates endothelial dysfunction in renal failure: new effect of asymmetric dimethylarginine. Kidney Int. 2012;81(8):762–8.PubMedCrossRef
28.
go back to reference Prowle JR, Ishikawa K, May CN, Bellomo R. Renal plasma flow and glomerular filtration rate during acute kidney injury in man. Ren Fail. 2010;32(3):349–55.PubMedCrossRef Prowle JR, Ishikawa K, May CN, Bellomo R. Renal plasma flow and glomerular filtration rate during acute kidney injury in man. Ren Fail. 2010;32(3):349–55.PubMedCrossRef
29.
go back to reference Conrad KP. Mechanisms of renal vasodilation and hyperfiltration during pregnancy. J Soc Gynecol Invest. 2004;11(7):438–48.CrossRef Conrad KP. Mechanisms of renal vasodilation and hyperfiltration during pregnancy. J Soc Gynecol Invest. 2004;11(7):438–48.CrossRef
30.
go back to reference Cachofeiro V, Goicochea M, de Vinuesa SG, Oubina P, Lahera V, Luno J. Oxidative stress and inflammation, a link between chronic kidney disease and cardiovascular disease. Kidney Int Suppl. 2008;111:S4–9.PubMedCrossRef Cachofeiro V, Goicochea M, de Vinuesa SG, Oubina P, Lahera V, Luno J. Oxidative stress and inflammation, a link between chronic kidney disease and cardiovascular disease. Kidney Int Suppl. 2008;111:S4–9.PubMedCrossRef
31.
go back to reference Umeji K, Umemoto S, Itoh S, Tanaka M, Kawahara S, Fukai T, et al. Comparative effects of pitavastatin and probucol on oxidative stress, Cu/Zn superoxide dismutase, PPAR-gamma, and aortic stiffness in hypercholesterolemia. Am J Physiol Heart Circ Physiol. 2006;291(5):H2522–32.PubMedCrossRef Umeji K, Umemoto S, Itoh S, Tanaka M, Kawahara S, Fukai T, et al. Comparative effects of pitavastatin and probucol on oxidative stress, Cu/Zn superoxide dismutase, PPAR-gamma, and aortic stiffness in hypercholesterolemia. Am J Physiol Heart Circ Physiol. 2006;291(5):H2522–32.PubMedCrossRef
32.
go back to reference Chinen I, Shimabukuro M, Yamakawa K, Higa N, Matsuzaki T, Noguchi K, et al. Vascular lipotoxicity: endothelial dysfunction via fatty-acid-induced reactive oxygen species overproduction in obese Zucker diabetic fatty rats. Endocrinology. 2007;148(1):160–5.PubMedCrossRef Chinen I, Shimabukuro M, Yamakawa K, Higa N, Matsuzaki T, Noguchi K, et al. Vascular lipotoxicity: endothelial dysfunction via fatty-acid-induced reactive oxygen species overproduction in obese Zucker diabetic fatty rats. Endocrinology. 2007;148(1):160–5.PubMedCrossRef
33.
go back to reference Yagi S, Akaike M, Aihara K, Ishikawa K, Iwase T, Ikeda Y, et al. Endothelial nitric oxide synthase-independent protective action of statin against angiotensin II-induced atrial remodeling via reduced oxidant injury. Hypertension. 2010;55(4):918–23.PubMedCrossRef Yagi S, Akaike M, Aihara K, Ishikawa K, Iwase T, Ikeda Y, et al. Endothelial nitric oxide synthase-independent protective action of statin against angiotensin II-induced atrial remodeling via reduced oxidant injury. Hypertension. 2010;55(4):918–23.PubMedCrossRef
34.
go back to reference Ren Y, Carretero OA, Garvin JL. Mechanism by which superoxide potentiates tubuloglomerular feedback. Hypertension. 2002;39(2 Pt 2):624–8.PubMedCrossRef Ren Y, Carretero OA, Garvin JL. Mechanism by which superoxide potentiates tubuloglomerular feedback. Hypertension. 2002;39(2 Pt 2):624–8.PubMedCrossRef
35.
go back to reference Honjo T, Inoue N, Shiraki R, Kobayashi S, Otsui K, Takahashi M, et al. Endothelial urocortin has potent antioxidative properties and is upregulated by inflammatory cytokines and pitavastatin. J Vasc Res. 2006;43(2):131–8.PubMedCrossRef Honjo T, Inoue N, Shiraki R, Kobayashi S, Otsui K, Takahashi M, et al. Endothelial urocortin has potent antioxidative properties and is upregulated by inflammatory cytokines and pitavastatin. J Vasc Res. 2006;43(2):131–8.PubMedCrossRef
Metadata
Title
The administration of pitavastatin augments creatinine clearance associated with reduction in oxidative stress parameters: acute and early effects
Authors
Hirokazu Kakuda
Keizo Kanasaki
Daisuke Koya
Noboru Takekoshi
Publication date
01-04-2013
Publisher
Springer Japan
Published in
Clinical and Experimental Nephrology / Issue 2/2013
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-012-0689-0

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