Uric Acid Is a Biomarker of Oxidative Stress in the Failing Heart: Lessons Learned from Trials With Allopurinol and SGLT2 Inhibitors
Open accessAbstract
Hyperuricemia increases the risk of heart failure, and higher levels of serum uric acid are seen in patients who have worse ventricular function, functional capacity, and prognosis. Heart failure is also accompanied by an upregulation of xanthine oxidase, the enzyme that catalyzes the formation of uric acid and a purported source of reactive oxygen species. However, the available evidence does not support the premise that either uric acid or the activation of xanthine oxidase has direct injurious effects on the heart in the clinical setting. Xanthine oxidase inhibitors (allopurinol and oxypurinol) have had little benefit and may exert detrimental effects in patients with chronic heart failure in randomized controlled trials, and the more selective and potent inhibitor febuxostat increases the risk of cardiovascular death more than allopurinol. Instead, the available evidence indicates that changes in xanthine oxidase and uric acid are biomarkers of oxidative stress (particularly in heart failure) and that xanthine oxidase may provide an important source of nitric oxide that quenches the injurious effects of reactive oxygen species. A primary determinant of the cellular redox state is nicotinamide adenine dinucleotide, whose levels drive an inverse relationship between xanthine oxidase and sirtuin-1, a nutrient deprivation sensor that exerts important antioxidant and cardioprotective effects. Interestingly, sodium-glucose cotransporter 2 inhibitors induce a state of nutrient deprivation that includes activation of sirtuin-1, suppression of xanthine oxidase, and lowering of serum uric acid. The intermediary role of sirtuin-1 in both uric acid-lowering and cardioprotection may explain why, in mediation analyses of large-scale cardiovascular trials, the effect of sodium-glucose cotransporter 2 inhibitors to decrease serum uric acid is a major predictor of the ability of these drugs to decrease serious heart failure events.
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Erythrocytosis and uric acid lowering may represent biomarkers for the effect of SGLT2 inhibitors to promote energy deprivation signaling and reduce oxidative stress.
“Both erythrocytosis and uric acid lowering may represent biomarkers for the effect of SGLT2 inhibitors to promote energy deprivation signaling and reduce oxidative stress.”
From Effect of Empagliflozin on the Clinical Stability of Patients With Heart Failure and a Reduced Ejection Fraction: The EMPEROR-Reduced Trial (2021) · cites this paper as [35]
Cites
Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout
White, W. B., Saag, K. G., Becker, M. A., BORER, J. S., Gorelick, P. B., Whelton, A., Hunt, B., Castillo, M., & Gunawardhana, L. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1710895 · Cited by 912 · see citing works
Inzucchi, S. E., Zinman, B., Fitchett, D., Wanner, C., Ferrannini, E., Schumacher, M., Schmoor, C., Ohneberg, K., Johansen, O. E., George, J. T., et al. (2018) · Diabetes Care · doi:10.2337/dc17-1096 · Cited by 740 · see citing works
Casella, G., Carr, E., Davies, J. I., Belch, J. J. F., & Struthers, A. D. (2006) · Circulation · doi:10.1161/circulationaha.106.651117 · Cited by 574 · see citing works
Vascular Oxidative Stress and Endothelial Dysfunction in Patients With Chronic Heart Failure
Landmesser, U., Spiekermann, S., Dikalov, S., Tatge, H., Wilke, R., Kohler, C., Harrison, D. G., Hornig, B., & Drexler, H. (2002) · Circulation · doi:10.1161/01.cir.0000041431.57222.af · Cited by 517 · see citing works
Redox regulation of SIRT1 in inflammation and cellular senescence
Hwang, J.-W., Yao, H., Caito, S., Sundar, I. K., & Rahman, I. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.03.015 · Cited by 503 · see citing works
Sirtuins and NAD + in the Development and Treatment of Metabolic and Cardiovascular Diseases
Kane, A. E., & Sinclair, D. A. (2018) · Circulation Research · doi:10.1161/circresaha.118.312498 · Cited by 490 · see citing works
An Extremely Potent Inhibitor of Xanthine Oxidoreductase
Okamoto, K., Eger, B. T., Nishino, T., Kondo, S., Pai, E. F., & Nishino, T. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m208307200 · Cited by 434 · see citing works
Li, X., Meng, X., Timofeeva, M. N., Tzoulaki, I., Tsilidis, K. K., Ioannidis, J. P. A., Campbell, H. J., & Τheodoratou, E. (2017) · BMJ · doi:10.1136/bmj.j2376 · Cited by 402 · see citing works
Impact of Oxypurinol in Patients With Symptomatic Heart Failure
Hare, J. M., Mangal, B., Brown, J., Fisher, C., Freudenberger, R., Colucci, W. S., Mann, D. L., Liu, P., Givertz, M. M., & Schwarz, R. P. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.01.068 · Cited by 392 · see citing works
Nishino, T., Okamoto, K., Eger, B. T., PAI, E. F., & Nishino, T. (2008) · FEBS Journal · doi:10.1111/j.1742-4658.2008.06489.x · Cited by 387 · see citing works
Massey, V., Komai, H., Palmer, G., & Elion, G. B. (1970) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)63065-0 · Cited by 380 · see citing works
Serum uric acid as an index of impaired oxidative metabolism in chronic heart failure.
Leyva, F., Anker, S., Swan, J. W., Godsland, I., Wingrove, C. S., Chua, T., Stevenson, J., & Coats, A. (1997) · European Heart Journal · doi:10.1093/oxfordjournals.eurheartj.a015352 · Cited by 366 · see citing works
URic Acid and Risk Of Heart Failure: A Systematic Review and Meta-Analysis
Huang, H., Huang, B., Li, Y., Huang, Y., Li, J., Yao, H., Jing, X., Chen, J., & Wang, J. (2013) · European Journal of Heart Failure · doi:10.1093/eurjhf/hft132 · Cited by 338 · see citing works
Normalization of NAD + Redox Balance as a Therapy for Heart Failure
Lee, C. F., Chavez, J. D., Garcia‐Menendez, L., Choi, Y. S., Roe, N. D., Chiao, Y. A., Edgar, J. S., Goo, Y. A., Goodlett, D. R., Bruce, J. E., et al. (2016) · Circulation · doi:10.1161/circulationaha.116.022495 · Cited by 337 · see citing works
Selectivity of febuxostat, a novel non-purine inhibitor of xanthine oxidase/xanthine dehydrogenase
Takano, Y., Hase-Aoki, K., Horiuchi, H., Zhao, L., Kasahara, Y., Kondo, S., & Becker, M. A. (2005) · Life Sciences · doi:10.1016/j.lfs.2004.10.031 · Cited by 336 · see citing works
Zhao, Y., Xu, L., Tian, D., Xia, P., Zheng, H., Wang, L., & Chen, L. (2018) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13101 · Cited by 333 · see citing works
Xanthine Oxidoreductase‐Derived Reactive Species: Physiological and Pathological Effects
Battelli, M. G., Polito, L., Bortolotti, M., & Bolognesi, A. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/3527579 · Cited by 314 · see citing works
Uric acid in chronic heart failure: a marker of chronic inflammation.
Leyva, F., Anker, S., Godsland, I., Teixeira, M. M., Hellewell, P., Kox, W., Poole-wilson, P., & Coats, A. (1998) · European Heart Journal · doi:10.1053/euhj.1998.1188 · Cited by 303 · see citing works
Givertz, M. M., Anstrom, K. J., Redfield, M. M., Deswal, A., Haddad, H., Butler, J., Tang, W. H. W., Dunlap, M. E., LeWinter, M. M., Mann, D. L., et al. (2015) · Circulation · doi:10.1161/circulationaha.114.014536 · Cited by 296 · see citing works
Shao, Q., Meng, L., Lee, S., Tse, G., Gong, M., Zhang, Z., Zhao, J., Zhao, Y., Li, G., & Liu, T. (2019) · Cardiovascular Diabetology · doi:10.1186/s12933-019-0964-4 · Cited by 295 · see citing works
Sirtuins and Type 2 Diabetes: Role in Inflammation, Oxidative Stress, and Mitochondrial Function
Kitada, M., Ogura, Y., Monno, I., & Koya, D. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00187 · Cited by 294 · see citing works
Virdis, A., Masi, S., Casiglia, E., Tikhonoff, V., Cicero, A. F. G., Ungar, A., Rivasi, G., Salvetti, M., Barbagallo, C. M., Bombelli, M., et al. (2019) · Hypertension · doi:10.1161/hypertensionaha.119.13643 · Cited by 279 · see citing works
Shear stress, SIRT1, and vascular homeostasis
Chen, Z., Peng, I., Cui, X., Li, Y.-S. J., Chien, S., & Shyy, J. Y.-J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1003833107 · Cited by 278 · see citing works
Schulz, E., Wenzel, P., Münzel, T. F., & Daiber, A. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4609 · Cited by 253 · see citing works
Cantu-Medellin, N., & Kelley, E. E. (2013) · Redox Biology · doi:10.1016/j.redox.2013.05.002 · Cited by 237 · see citing works
SGLT2 inhibition reprograms systemic metabolism via FGF21-dependent and -independent mechanisms
Osataphan, S. A., Macchi, C., Singhal, G., CHIMENE-WEISS, J. I., Sales, V., Kozuka, C., Dreyfuss, J. M., Pan, H., Tangcharoenpaisan, Y., Morningstar, J. E., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.123130 · Cited by 229 · see citing works
The role of xanthine oxidoreductase and uric acid in metabolic syndrome
Battelli, M. G., Bortolotti, M., Polito, L., & Bolognesi, A. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.05.003 · Cited by 210 · see citing works
Chlorthalidone Reduces Cardiovascular Events Compared With Hydrochlorothiazide
Dorsch, M. P., Gillespie, B. W., Erickson, S. R., Bleske, B. E., & Weder, A. B. (2011) · Hypertension · doi:10.1161/hypertensionaha.110.161505 · Cited by 197 · see citing works
Uric Acid-Lowering Treatment With Benzbromarone in Patients With Heart Failure
Oginö, K., Kato, M., Furuse, Y., Kinugasa, Y., Ishida, K., Osaki, S., Kinugawa, T., Igawa, O., Hisatome, I., Shigemasa, C., et al. (2009) · Circulation Heart Failure · doi:10.1161/circheartfailure.109.868604 · Cited by 191 · see citing works
SGLT2 inhibition and renal urate excretion: role of luminal glucose, GLUT9, and URAT1
Novikov, A., Fu, Y., Huang, W., Freeman, B., Patel, R., van Ginkel, C., Koepsell, H., Busslinger, M., Onishi, A., Nespoux, J., et al. (2019) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00462.2018 · Cited by 186 · see citing works
Nitric oxide and nitric oxide synthase isoforms in the normal, hypertrophic, and failing heart
Umar, S., & van der Laarse, A. (2010) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-009-0219-x · Cited by 182 · see citing works
Umino, H., Hasegawa, K., Minakuchi, H., Muraoka, H., Kawaguchi, T., Kanda, T., Tokuyama, H., Wakino, S., & Itoh, H. (2018) · Scientific Reports · doi:10.1038/s41598-018-25054-y · Cited by 163 · see citing works
Ahmed, M. I., Gladden, J. D., Litovsky, S. H., Lloyd, S. G., Gupta, H., Inusah, S., Denney, T. S., Powell, P. C., McGiffin, D. C., & Dell’Italia, L. J. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.08.074 · Cited by 146 · see citing works
Ischemia-reperfusion in humans. Appearance of xanthine oxidase activity.
Friedl, H. P., Smith, D. J., Till, G. O., Thomson, P. D., Louis, D. S., & Ward, P. A. (1990) · Europe PMC (PubMed Central) · Cited by 145 · see citing works
Mediators of the Effects of Canagliflozin on Heart Failure in Patients With Type 2 Diabetes
Li, J., Woodward, M., Perkovic, V., Figtree, G. A., Heerspink, H. J. L., Mahaffey, K. W., de Zeeuw, D., Vercruysse, F., Shaw, W., Matthews, D. R., et al. (2020) · JACC: Heart Failure · doi:10.1016/j.jchf.2019.08.004 · Cited by 144 · see citing works
Uric acid as radical scavenger and antioxidant in the heart
Becker, B. F., Reinholz, N., �z�elik, T., Leipert, B., & Gerlach, E. (1989) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/bf00370582 · Cited by 131 · see citing works
Park, S., Farooq, M. A., Gaertner, S., Bruckert, C., Qureshi, A. W., Lee, H.-H., Benrahla, D., Pollet, B., Stéphan, D., Ohlmann, P., et al. (2020) · Cardiovascular Diabetology · doi:10.1186/s12933-020-00997-7 · Cited by 127 · see citing works
Enhanced Expression and Activity of Xanthine Oxidoreductase in the Failing Heart
de Jong, J. W., Schoemaker, R. G., de Jonge, R., Bernocchi, P., Keijzer, E., Harrison, R., Sharma, H. S., & Ceconi, C. (2000) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.2000.1240 · Cited by 120 · see citing works
Regulation of Xanthine Oxidoreductase Protein Expression by Hydrogen Peroxide and Calcium
McNally, J. S., Saxena, A., Cai, H. “., Dikalov, S., & Harrison, D. G. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000170827.16296.6e · Cited by 115 · see citing works
Organ distribution and molecular forms of human xanthine dehydrogenase/xanthine oxidase protein.
Sarnesto, A., Linder, N., & Raivio, K. O. (1996) · PubMed · Cited by 114 · see citing works
Zhang, Z., Blake, D. R., Stevens, C. R., Kanuler, J. M., Ward, P. G., Symons, M. C. R., Benboubetra, M., & Harrison, R. (1998) · Free Radical Research · doi:10.3109/10715769809065801 · Cited by 110 · see citing works
Packer, M. (2020) · Circulation · doi:10.1161/circulationaha.119.045561 · Cited by 110 · see citing works
Self-citationvon Lueder, T. G., Girerd, N., Atar, D., et al. (2015) · European Journal of Heart Failure · doi:10.1002/ejhf.419 · Cited by 103 · see citing works
Stoichiometric Inhibition of Reduced Xanthine Oxidase by Hydroxypyrazolo[3,4-d]pyrimidines
Spector, T., & Johns, D. G. (1970) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)62820-0 · Cited by 85 · see citing works
Sakai, H., Tsutamoto, T., Tsutsui, T., Tanaka, T., Ishikawa, C., & Horie, M. (2006) · Circulation Journal · doi:10.1253/circj.70.1006 · Cited by 85 · see citing works
Xanthine oxidase inhibitor allopurinol attenuates the development of diabetic cardiomyopathy
Rajesh, M., Mukhopadhyay, P., Bátkai, S., Mukhopadhyay, B., Patel, V., Haskó, G., Szabó, C., Mabley, J. G., Liaudet, L., & Pacher, P. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00564.x · Cited by 84 · see citing works
Johnson, R. J., Gaucher, E. A., Sautin, Y. Y., Henderson, G. N., Angerhofer, A., & Benner, S. A. (2008) · Medical Hypotheses · doi:10.1016/j.mehy.2008.01.017 · Cited by 83 · see citing works
Xu, X. Y., Hu, X., Lu, Z., Zhang, P., Zhao, L., Wessale, J. L., Bache, R. J., & Chen, Y. (2008) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2008.06.006 · Cited by 81 · see citing works
Otaki, Y., Watanabe, T., Kinoshita, D., Yokoyama, M., Takahashi, T., Toshima, T., Sugai, T., Murase, T., Nakamura, T., Nishiyama, S., et al. (2016) · International Journal of Cardiology · doi:10.1016/j.ijcard.2016.11.077 · Cited by 81 · see citing works
Vaduganathan, M., Greene, S. J., Ambrosy, A. P., Mentz, R. J., Subacius, H. P., Chioncel, O., Maggioni, A. P., Swedberg, K. B., Zannad, F. M., Konstam, M. A., et al. (2014) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2014.09.008 · Cited by 79 · see citing works
Enhanced XOR activity in eNOS-deficient mice
Peleli, M., Zollbrecht, C., Montenegro, M. F., Hezel, M. P., Zhong, J., Persson, E., Holmdahl, R., Weitzberg, E., Lundberg, J. O., & Carlström, M. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.09.004 · Cited by 76 · see citing works
Purification and partial characterization of xanthine oxidase from human milk
Abadeh, S., Killacky, J., Benboubetra, M., & Harrison, R. (1992) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(92)90157-p · Cited by 75 · see citing works
Washio, K., Kusunoki, Y., Murase, T., Nakamura, T., Osugi, K., Ohigashi, M., Sukenaga, T., Ochi, F., Matsuo, T., Katsuno, T., et al. (2017) · Metabolism · doi:10.1016/j.metabol.2017.01.031 · Cited by 72 · see citing works
Swe, M. T., Thongnak, L., Jaikumkao, K., Pongchaidecha, A., Chatsudthipong, V., & Lungkaphin, A. (2019) · Clinical Science · doi:10.1042/cs20190863 · Cited by 71 · see citing works
Urate produced during hypoxia protects heart proteins from peroxynitrite-mediated protein nitration
Teng, R., Ye, Y.-Z. U., Parks, D. A., et al. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)01020-1 · Cited by 68 · see citing works
Kuppusamy, U. R., Indran, M., & Rokiah, P. (2005) · Diabetic Medicine · doi:10.1111/j.1464-5491.2005.01630.x · Cited by 66 · see citing works
Kim, J., Lee, Y., You, Y., Moon, M. K., Yoon, K., Ahn, Y., & Ko, S. (2018) · Journal of Cellular Biochemistry · doi:10.1002/jcb.28141 · Cited by 63 · see citing works
Safranow, K., Dziedziejko, V., Rzeuski, R., Czyżycka, E., Wojtarowicz, A., Bińczak‐Kuleta, A., Jakubowska, K., Olszewska, M. J., Ciechanowicz, A., Kornacewicz‐Jach, Z., et al. (2009) · Tissue Antigens · doi:10.1111/j.1399-0039.2009.01332.x · Cited by 61 · see citing works
Mogensen, U. M., Køber, L., Jhund, P. S., Desai, A. S., Senni, M., Kristensen, S. L., Dukát, A., Chen, C., Ramires, F. J. A., Lefkowitz, M. P., et al. (2017) · European Journal of Heart Failure · doi:10.1002/ejhf.1056 · Cited by 61 · see citing works
Self-citationPeroxynitrite Induces the Conversion of Xanthine Dehydrogenase to Oxidase in Rabbit Liver
Sakuma, S., Fujimoto, Y., Sakamoto, Y., Uchiyama, T., Yoshioka, K., Nishida, H., & Fujita, T. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.5983 · Cited by 59 · see citing works
SIRT1 prevents hyperuricemia via the PGC-1α/PPARγ-ABCG2 pathway
Wang, J., Zhu, X., Liu, L., Xue, Y., Yang, X., & Zou, H.-J. (2016) · Endocrine · doi:10.1007/s12020-016-0896-7 · Cited by 57 · see citing works
Gladden, J. D., Zelickson, B. R., Wei, C.-C., Ulasova, E., Zheng, J., Ahmed, M. I., Chen, Y., Bamman, M., Ballinger, S., Darley-Usmar, V., et al. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.08.022 · Cited by 54 · see citing works
Changes in serum uric acid levels and cardiovascular events: A meta-analysis
Savarese, G., Ferri, C., Trimarco, B., Rosano, G. M. C., Dellegrottaglie, S., Losco, T., Casaretti, L., D’Amore, C., Gambardella, F., Prastaro, M., et al. (2013) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2013.03.001 · Cited by 50 · see citing works
Verma, S., Ji, Q., Bhatt, D. L., Mazer, C. D., Al-Omran, M. A., Inzucchi, S. E., Wanner, C., Ofstad, A. P., Zwiener, I., George, J. T., et al. (2020) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13991 · Cited by 46 · see citing works
Wannamethee, S. G., Papacosta, O., LENNON, L. T., et al. (2017) · International Journal of Cardiology · doi:10.1016/j.ijcard.2017.11.083 · Cited by 43 · see citing works
Fujimura, Y., Yamauchi, Y., Murase, T., Nakamura, T., Fujita, S.-I., Fujisaka, T., Ito, T., Sohmiya, K., Hoshiga, M., & Ishizaka, N. (2017) · PLoS ONE · doi:10.1371/journal.pone.0182699 · Cited by 40 · see citing works
Lappas, M., Andrikopoulos, S., & Permezel, M. (2012) · Journal of Endocrinology · doi:10.1530/joe-11-0355 · Cited by 39 · see citing works
Zhao, L., Roche, B. M., Wessale, J. L., Kijtawornrat, A., Lolly, J. L., Shemanski, D., & Hamlin, R. L. (2008) · Life Sciences · doi:10.1016/j.lfs.2007.12.010 · Cited by 34 · see citing works
Rousso, P., Buclin, T., Nussberger, J., et al. (1999) · Journal of Hypertension · doi:10.1097/00004872-199917030-00017 · Cited by 34 · see citing works
Mohamed, H. E., Asker, M. E.-S., Keshawy, M. M., Hasan, R. A., & Mahmoud, Y. K. (2020) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-020-03686-x · Cited by 34 · see citing works
Wang, P., Yang, X., Zhang, Z., Song, J., Guan, Y., Zou, D., & Miao, C. (2016) · Metabolism · doi:10.1016/j.metabol.2016.03.006 · Cited by 32 · see citing works
Khadka, D., Kim, H., Oh, G., et al. (2018) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2018.10.001 · Cited by 30 · see citing works
Kanbay, M., Afşar, B., Siriopol, D. C., Di̇nçer, N., Erden, N., Yılmaz, O., Sag, A. A., Kuwabara, M., Cherney, D., Rossignol, P., et al. (2020) · Angiology · doi:10.1177/0003319719897509 · Cited by 29 · see citing works
Huang, X., Li, H., Shi, L., et al. (2008) · Chemistry & Biodiversity · doi:10.1002/cbdv.200890059 · Cited by 24 · see citing works
Serum uric acid as an index of impaired renal function in congestive heart failure
Tian, Y., Chen, Y., Bao, D., et al. (2012) · 老年心脏病学杂志：英文版 · doi:10.3724/sp.j.1263.2011.11281 · Cited by 23 · see citing works
Kim, H., Baek, C. H., Chang, J. W., Yang, W. S., & Lee, S. K. (2019) · Clinical and Experimental Nephrology · doi:10.1007/s10157-019-01804-8 · Cited by 23 · see citing works
Oki, Y., Kawai, M., Minai, K., Ogawa, K., Inoue, Y., Morimoto, S., Tanaka, T. D., Nagoshi, T., Ogawa, T., & Yoshimura, M. (2019) · Scientific Reports · doi:10.1038/s41598-018-37053-0 · Cited by 19 · see citing works
Allopurinol improves myocardial reperfusion injury in a xanthine oxidase-free model.
Hopson, S. B., Lust, R. M., Sun, Y. S., Zeri, R. S., Morrison, R. F., Otaki, M., & Chitwood, W. R. (1995) · PubMed Central · Cited by 16 · see citing works
Predictors of reaching a serum uric acid goal in patients with gout and treated with febuxostat
Sheer, R. L., Null, K. D., Szymanski, K. A., et al. (2017) · ClinicoEconomics and Outcomes Research · doi:10.2147/ceor.s139939 · Cited by 14 · see citing works
Spironolactone increases serum uric acid levels in patients with chronic kidney disease
Cabrera, S., Edwards, N. C., Steeds, R. P., et al. (2013) · Journal of Human Hypertension · doi:10.1038/jhh.2013.66 · Cited by 12 · see citing works
Tan, Z., Dai, T., Zhong, X., Tian, Y., Leppo, M. K., & Gao, W. D. (2009) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2009.08.033 · Cited by 11 · see citing works
Karabacak, M., Doğan, A., Tayyar, Ş., & Baş, H. A. (2015) · Kardiologia Polska · doi:10.5603/kp.a2014.0190 · Cited by 7 · see citing works
Effect of allopurinol and benzbromarone on the concentration of uridine in plasma
Yamamoto, T., Moriwaki, Y., Takahashi, S., et al. (1997) · Metabolism · doi:10.1016/s0026-0495(97)90151-7 · Cited by 6 · see citing works
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Self-citation
- Authors
- Packer, M.
- Affiliations
- Baylor University Medical Center (US)
- Corresponding author
- Packer, Milton
- ORCID
- Packer, Milton
- Venue
- Journal of Cardiac Failure
- Publisher
- Elsevier BV
- Published
- 2020-11
- Volume
- 26
- Issue
- 11
- Pages
- 977-984
- ISSN
- 1071-9164 (ISSN-L)
- OpenAlex
- W3082543969
- Cited by
- 95
- References
- 83
- Citations by year
- 2026: 11 · 2025: 18 · 2024: 17 · 2023: 18 · 2022: 21 · 2021: 8 · 2020: 1
- FWCI
- 7.53
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Cardiac Failure (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Nephrology › Gout, Hyperuricemia, Uric Acid
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- uric acid, hyperuricemia, heart failure, oxidative stress, xanthine oxidase, allopurinol, febuxostat, oxypurinol, SGLT2 inhibitors, SIRT1, NAD+, nitric oxide, reactive oxygen species, biomarkers, cardioprotection, mediation analysis
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Allopurinol, Enzyme Inhibitors, Heart Failure, Humans, Uric Acid, Biomarkers, Oxidative Stress
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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