Spironolactone Attenuates Oxidative Stress in Patients With Chronic Kidney Disease
2008; Lippincott Williams & Wilkins; Volume: 52; Issue: 5 Linguagem: Inglês
10.1161/hypertensionaha.108.120568
ISSN1524-4563
AutoresMarcin Renke, Leszek Tylicki, Narcyz Knap, Przemysław Rutkowski, Alexander Neuwelt, Wojciech Larczyński, Michał Woźniak, Piotr Rutkowski,
Tópico(s)Potassium and Related Disorders
ResumoHomeHypertensionVol. 52, No. 5Spironolactone Attenuates Oxidative Stress in Patients With Chronic Kidney Disease Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBSpironolactone Attenuates Oxidative Stress in Patients With Chronic Kidney Disease Marcin Renke and Leszek Tylicki Narcyz Knap Przemysław Rutkowski Alexander Neuwelt Wojciech Larczyński Michał Woźniak Bolesław Rutkowski Marcin RenkeMarcin Renke Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland and Leszek TylickiLeszek Tylicki Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland Narcyz KnapNarcyz Knap Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland Przemysław RutkowskiPrzemysław Rutkowski Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland Alexander NeuweltAlexander Neuwelt Blood Brain Barrier and Neuro-Oncology Program, Oregon Health and Science University, Portland, Ore Wojciech LarczyńskiWojciech Larczyński Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland Michał WoźniakMichał Woźniak Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland Bolesław RutkowskiBolesław Rutkowski Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland Originally published29 Sep 2008https://doi.org/10.1161/HYPERTENSIONAHA.108.120568Hypertension. 2008;52:e132–e133Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: September 29, 2008: Previous Version 1 To the Editor:In one of the latest issues of Hypertension, Michea et al1 reported that the mineralocorticoid receptor antagonist spironolactone attenuates cardiac hypertrophy and oxidative stress of the heart in uremic rats. The results of our recent clinical study indicate that spironolactone acts to decrease the amount of oxidative stress in patients being treated for chronic kidney disease. In an open, randomized, crossover study, 16 white adult patients (10 men and 6 women; mean age: 41 years) with nondiabetic proteinuric chronic kidney disease were evaluated to test the hypothesis that spironolactone combined with standard nephroprotective therapy may act as a clinically beneficial antioxidant.All of the study participants, during a preliminary period of 8 weeks, received the angiotensin-converting enzyme inhibitor cilazapril (5 mg), angiotensin II type 1 receptor blocker telmisartan (80 mg), and diuretic hydrochlorothiazide (12.5 mg), reducing the blood pressure to <130/80 mm Hg. The trial treatment was either based solely on the unchanged double blockade of the renin-angiotensin system or combined with 25 mg of spironolactone, thus providing triple renin-angiotensin system blockade during the first 2 months of the study, with the alternative being used for the next 2 months. A commercial ELISA kit (Cayman Chemical Co) was then used to measure the urinary excretion of 15-F2t-isoprostane, widely accepted as a reliable and sensitive marker of oxidative stress in the human body.2It was found that spironolactone significantly reduced urinary levels of 15-F2t-isoprostane relative to the control group (ANOVA P=0.035; posthoc P=0.041), with no change observed in systemic blood pressure or serum creatinine levels (Table). This finding may be of clinical relevance, because 15-F2t-isoprostane isoprostane has biological activity as a potent renal vasoconstrictor3 and has been implicated as a causative mediator in hepatorenal syndrome.4Table. Serum Creatinine and Urinary Excretion of 15-F2t-IsoprostaneParameterRandomizationSpironolactoneControlEnd of StudySerum creatinine, mean±SEM, mg/dL1.12±0.081.16±0.101.13±0.111.09±0.10Urinary 15-F2t-isoprostane, geometric mean (95% CI), ng/mg of creatinine0.76 (0.48 to 2.48)0.65 (0.51 to 0.98)0.94 (0.67 to 2.55)0.91 (0.55 to 2.51)Interestingly, Furumatsu et al5 recently observed a beneficial effect from the incorporation of spironolactone into a combined treatment regimen consisting of angiotensin-converting enzyme inhibitor and angiotensin II type 1 receptor blocker for use against chronic kidney disease; Furumatsu et al5 specifically noted improved intrarenal hemodynamics, as well as decreased proteinuria levels, in patients receiving spironolactone. Thus, taken together with the findings of previous studies, our results indicate that spironolactone may be a useful addition to standard nephroprotective therapy, playing a beneficial role as a clinically effective antioxidant.Source of FundingThe study was fully supported by Medical University of Gdansk via ST-U grant.DisclosuresNone.1 Michea L, Villagrán A, Urzúa A, Kuntsmann S, Venegas P, Carrasco L, Gonzalez M, Marusic ET. Mineralocorticoid receptor antagonism attenuates cardiac hypertrophy and prevents oxidative stress in uremic rats. Hypertension. 2008; 52: 1–6.LinkGoogle Scholar2 Fam SS, Morrow JD. The isoprostanes: unique products of arachidonic acid oxidation-a review. Curr Med Chem. 2003; 10: 1723–1740.CrossrefMedlineGoogle Scholar3 Takahashi K, Nammour TM, Fukunaga M, Ebert J, Morrow JD, Roberts LJ, Hoover RL, Badr KF. Glomerular actions of a free radical-generated novel prostaglandin, 8-epi-prostaglandin F2 alpha, in the rat. Evidence for interaction with thromboxane A2 receptors. J Clin Invest. 1992; 90: 136–141.CrossrefMedlineGoogle Scholar4 Morrow JD, Moore KP, Awad JA, Ravenscraft MD, Marini G, Badr KF, Williams R, Roberts LJ. Marked overproduction of non-cyclooxygenase derived prostanoids (F2-isoprostanes) in the hepatorenal syndrome. J Lipid Mediat. 1993; 6: 417–420.MedlineGoogle Scholar5 Furumatsu Y, Nagasawa Y, Tomida K, Mikami S, Kaneko T, Okada N, Tsubakihara Y, Imai E, Shoji T. Effect of renin-angiotensin-aldosterone system triple blockade on non-diabetic renal disease: addition of an aldosterone blocker, spironolactone, to combination treatment with an angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker. Hypertens Res. 2008; 31: 59–67.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Patel V, Joharapurkar A and Jain M (2020) Role of mineralocorticoid receptor antagonists in kidney diseases, Drug Development Research, 10.1002/ddr.21760, 82:3, (341-363), Online publication date: 1-May-2021. Heshmati N, Shahgheibi S, Nikkhoo B, Amini S and Abdi M (2016) Association of Prooxidant–Antioxidant Balance with Clinical and Laboratory Parameters and Its Relation to Different Drug Regimens in Polycystic Ovary Syndrome Women with Normal BMI, Indian Journal of Clinical Biochemistry, 10.1007/s12291-016-0613-6, 32:3, (315-322), Online publication date: 1-Jul-2017. McCurley A and Jaffe I (2012) Mineralocorticoid receptors in vascular function and disease, Molecular and Cellular Endocrinology, 10.1016/j.mce.2011.06.014, 350:2, (256-265), Online publication date: 1-Mar-2012. Michea L and Marusic E (2008) Response to Spironolactone Attenuates Oxidative Stress in Patients With Chronic Kidney Disease, Hypertension, 52:5, (e134-e134), Online publication date: 1-Nov-2008. Zabul P, Wozniak M, Slominski A, Preis K, Gorska M, Korozan M, Wieruszewski J, Zmijewski M, Zabul E, Tuckey R, Kuban-Jankowska A, Mickiewicz W and Knap N (2015) A Proposed Molecular Mechanism of High-Dose Vitamin D3 Supplementation in Prevention and Treatment of Preeclampsia, International Journal of Molecular Sciences, 10.3390/ijms160613043, 16:12, (13043-13064) Bolignano D, Palmer S, Navaneethan S and Strippoli G (2014) Aldosterone antagonists for preventing the progression of chronic kidney disease, Cochrane Database of Systematic Reviews, 10.1002/14651858.CD007004.pub3 November 2008Vol 52, Issue 5 Advertisement Article InformationMetrics https://doi.org/10.1161/HYPERTENSIONAHA.108.120568PMID: 18824658 Originally publishedSeptember 29, 2008 PDF download Advertisement SubjectsClinical StudiesEpidemiologyOxidant Stress
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