Rationale and design for Lowering-hyperUricaemia treatment on cardiovascular outcoMes In peritoNeal diAlysis patients: a prospective, multicentre, double-blind, randomised controlled trial (LUMINA)

Wei Chen, Naya Huang, Haiping Mao, Xiao Yang, Qian Zhou, Lanping Jiang, Jun Ding, Qiong Feng, Xueqing Yu, Wei Chen, Naya Huang, Haiping Mao, Xiao Yang, Qian Zhou, Lanping Jiang, Jun Ding, Qiong Feng, Xueqing Yu

Abstract

Introduction: The prevalence of hyperuricaemia in peritoneal dialysis patients is quite high. Studies have demonstrated a correlation between hyperuricaemia and cardiovascular disease and treatment of hyperuricaemia reportedly reduces cardiovascular risk in patients with chronic kidney disease. However, whether hyperuricaemia treatment benefits cardiovascular outcomes in continuous ambulatory peritoneal dialysis (CAPD) patients is not yet known.

Methods and analyses: This prospective, multicentre, double-blind, randomised controlled trial was designed to evaluate the effects of hyperuricaemia treatment on cardiovascular event risk in CAPD patients. Based on a power of 80%, with type I error α=0.05, two-sided test and 1:1 parallel control study, considering a dropout rate of 20%, a total of 548 eligible patients are expected to be randomly assigned to either the hyperuricaemia treatment group (febuxostat) or control group (placebo).

Ethics and dissemination: This study has been approved by the Medical Ethics Committee of the First Affiliated Hospital, Sun Yat-sen University and the ethics committees of other participating institutions. Written informed consent will be obtained from potential trial participants or authorised surrogates.The findings of the study will be disseminated through publications in peer-reviewed journals, and presentations at national and international conferences.

Trial registration number: NCT03200210. 25 June 2017. The trial was started on 13 July 2017, and is expected to end by 31 December 2022. Till 20 Jan 2020, a total of 548 patients have been recruited.

Protocol version: The protocol version number and date are YLT-1604-V2.0 and 15 December 2016.

Keywords: cardiology; dialysis; nephrology.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Study flow chart. CAPD, continuous ambulatory peritoneal dialysis; PET, peritoneal equilibrium test.

References

    1. Kubo S, Nishida Y, Kubota Y, et al. . Higher serum uric acid level is inversely associated with renal function assessed by cystatin C in a Japanese general population without chronic kidney disease: the Kobe study. BMC Nephrol 2019;20:117. 10.1186/s12882-019-1291-4
    1. Weiner DE, Tighiouart H, Elsayed EF, et al. . Uric acid and incident kidney disease in the community. J Am Soc Nephrol 2008;19:1204–11. 10.1681/ASN.2007101075
    1. Iseki K, Oshiro S, Tozawa M, et al. . Significance of hyperuricemia on the early detection of renal failure in a cohort of screened subjects. Hypertens Res 2001;24:691–7. 10.1291/hypres.24.691
    1. Dong J, Han Q-F, Zhu T-Y, et al. . The associations of uric acid, cardiovascular and all-cause mortality in peritoneal dialysis patients. PLoS One 2014;9:e82342. 10.1371/journal.pone.0082342
    1. Liu R, Han C, Wu D, et al. . Prevalence of hyperuricemia and gout in mainland China from 2000 to 2014: a systematic review and meta-analysis. Biomed Res Int 2015;2015:762820 10.1155/2015/762820
    1. Li Z, Liu Q, Mao H, et al. . Gender difference in the association of hyperuricemia with chronic kidney disease in southern China. Kidney Blood Press Res 2012;36:98–106. 10.1159/000341486
    1. Chen J-H, Chuang S-Y, Chen H-J, et al. . Serum uric acid level as an independent risk factor for all-cause, cardiovascular, and ischemic stroke mortality: a Chinese cohort study. Arthritis Rheum 2009;61:225–32. 10.1002/art.24164
    1. Fang J, Alderman MH. Serum uric acid and cardiovascular mortality the NHANES I epidemiologic follow-up study, 1971-1992. National health and nutrition examination survey. JAMA 2000;283:2404–10. 10.1001/jama.283.18.2404
    1. Krishnan E, Svendsen K, Neaton JD, et al. . Long-Term cardiovascular mortality among middle-aged men with gout. Arch Intern Med 2008;168:1104–10. 10.1001/archinte.168.10.1104
    1. Choi HK, Curhan G. Independent impact of gout on mortality and risk for coronary heart disease. Circulation 2007;116:894–900. 10.1161/CIRCULATIONAHA.107.703389
    1. Liese AD, Hense HW, Löwel H, et al. . Association of serum uric acid with all-cause and cardiovascular disease mortality and incident myocardial infarction in the MONICA Augsburg cohort. World Health organization monitoring trends and determinants in cardiovascular diseases. Epidemiology 1999;10:391–7. 10.1097/00001648-199907000-00006
    1. Niskanen LK, Laaksonen DE, Nyyssönen K, et al. . Uric acid level as a risk factor for cardiovascular and all-cause mortality in middle-aged men: a prospective cohort study. Arch Intern Med 2004;164:1546–51. 10.1001/archinte.164.14.1546
    1. Høieggen A, Alderman MH, Kjeldsen SE, et al. . The impact of serum uric acid on cardiovascular outcomes in the life study. Kidney Int 2004;65:1041–9. 10.1111/j.1523-1755.2004.00484.x
    1. Hozawa A, Folsom AR, Ibrahim H, et al. . Serum uric acid and risk of ischemic stroke: the ARIC study. Atherosclerosis 2006;187:401–7. 10.1016/j.atherosclerosis.2005.09.020
    1. Liu W-C, Hung C-C, Chen S-C, et al. . Association of hyperuricemia with renal outcomes, cardiovascular disease, and mortality. Clin J Am Soc Nephrol 2012;7:541–8. 10.2215/CJN.09420911
    1. Imazu M, Yamamoto H, Toyofuku M, et al. . Hyperinsulinemia for the development of hypertension: data from the Hawaii-Los Angeles-Hiroshima study. Hypertens Res 2001;24:531–6. 10.1291/hypres.24.531
    1. Bonora E, Capaldo B, Perin PC, et al. . Hyperinsulinemia and insulin resistance are independently associated with plasma lipids, uric acid and blood pressure in non-diabetic subjects. The GISIR database. Nutr Metab Cardiovasc Dis 2008;18:624–31. 10.1016/j.numecd.2007.05.002
    1. Kuwabara M, Borghi C, Cicero AFG, et al. . Elevated serum uric acid increases risks for developing high LDL cholesterol and hypertriglyceridemia: a five-year cohort study in Japan. Int J Cardiol 2018;261:183–8. 10.1016/j.ijcard.2018.03.045
    1. Lin J-D, Chiou W-K, Chang H-Y, et al. . Serum uric acid and leptin levels in metabolic syndrome: a quandary over the role of uric acid. Metabolism 2007;56:751–6. 10.1016/j.metabol.2007.01.006
    1. Wasada T, Katsumori K, Saeki A, et al. . [Hyperuricemia and insulin resistance]. Nihon Rinsho 1996;54:3293–6.
    1. Zhou Y, Zhao M, Pu Z, et al. . Relationship between oxidative stress and inflammation in hyperuricemia: analysis based on asymptomatic young patients with primary hyperuricemia. Medicine 2018;97:e13108. 10.1097/MD.0000000000013108
    1. Tomiyama H, Shiina K, Vlachopoulos C, et al. . Involvement of arterial stiffness and inflammation in Hyperuricemia-Related development of hypertension. Hypertension 2018;72:739–45. 10.1161/HYPERTENSIONAHA.118.11390
    1. Goicoechea M, de Vinuesa SG, Verdalles U, et al. . Effect of allopurinol in chronic kidney disease progression and cardiovascular risk. Clin J Am Soc Nephrol 2010;5:1388–93. 10.2215/CJN.01580210
    1. Siu Y-P, Leung K-T, Tong MK-H, et al. . Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. Am J Kidney Dis 2006;47:51–9. 10.1053/j.ajkd.2005.10.006
    1. Tsuruta Y, Nitta K, Akizawa T, et al. . Association between allopurinol and mortality among Japanese hemodialysis patients: results from the DOPPS. Int Urol Nephrol 2014;46:1833–41. 10.1007/s11255-014-0731-0
    1. Xia X, He F, Wu X, et al. . Relationship between serum uric acid and all-cause and cardiovascular mortality in patients treated with peritoneal dialysis. Am J Kidney Dis 2014;64:257–64. 10.1053/j.ajkd.2013.08.027
    1. Bose B, Badve SV, Hiremath SS, et al. . Effects of uric acid-lowering therapy on renal outcomes: a systematic review and meta-analysis. Nephrol Dial Transplant 2014;29:406–13. 10.1093/ndt/gft378
    1. Kojima S, Matsui K, Hiramitsu S, et al. . Febuxostat for cerebral and CaRdiorenovascular events prevention study. Eur Heart J 2019;40:1778–86. 10.1093/eurheartj/ehz119

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir