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BMC Nephrology
Published in: BMC Nephrology 1/2022

Open Access 01-12-2022 | Diabetes | Research

Hyperuricemia and diabetes mellitus when occurred together have higher risks than alone on all-cause mortality and end-stage renal disease in patients with chronic kidney disease

Authors: Cheng-Hung Li, Chia-Lin Lee, Yu-Cheng Hsieh, Cheng-Hsu Chen, Ming-Ju Wu, Shang-Feng Tsai

Published in: BMC Nephrology | Issue 1/2022

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Abstract

Introduction

Hyperuricemia and diabetes mellitus (DM) are associated with increased mortality risk in patients with chronic kidney disease (CKD). Here we aimed to evaluate the independent and joint risks of these two conditions on mortality and end stage kidney disease (ESKD) in CKD-patients.

Methods

This retrospective cohort study enrolled 4380 outpatients (with CKD stage 3–5) with mortality and ESKD linkage during a 7-year period (from 2007 to 2013). All-causes mortality and ESKD risks were analyzed by multivariable-adjusted Cox proportional hazards models (adjusted for age, sex, smoke, previous coronary arterial disease, blood pressure, and medications for hyperlipidemia, hyperuricemia and renin–angiotensin system inhibitors).

Results

Overall, 40.5% of participants had DM and 66.4% had hyperuricemia. In total, 356 deaths and 932 ESKD events occurred during the 7 years follow-up. With the multivariate analysis, increased risks for all-cause mortality were: hyperuricemia alone, HR = 1.48 (1–2.19); DM alone, and HR = 1.52 (1.02–2.46); DM and hyperuricemia together, HR = 2.12 (1.41–3.19). Similar risks for ESKD were: hyperuricemia alone, HR = 1.34 (1.03–1.73); DM alone, HR = 1.59 (1.15–2.2); DM and hyperuricemia together, HR = 2.46 (1.87–3.22).

Conclusions

DM and hyperuricemia are strongly associated with higher all-cause mortality and ESKD risk in patients with CKD stage 3–5. Hyperuricemia is similar to DM in terms of risk for all-cause mortality and ESKD. DM and hyperuricemia when occurred together further increase both risks of all-cause mortality and ESKD.
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Literature
1.
Meguid El Nahas A, Bello AK: Chronic kidney disease: the global challenge. Lancet (London, England) 2005:365(9456):331–340.
2.
Levey AS, Atkins R, Coresh J, Cohen EP, Collins AJ, Eckardt KU, et al. Chronic kidney disease as a global public health problem: approaches and initiatives - a position statement from kidney disease improving global outcomes. Kidney Int. 2007;72(3):247–59.PubMedCrossRef
3.
Anavekar NS, McMurray JJ, Velazquez EJ, Solomon SD, Kober L, Rouleau JL, et al. Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. N Engl J Med. 2004;351(13):1285–95.PubMedCrossRef
4.
Stengel B, Billon S, Van Dijk PC, Jager KJ, Dekker FW, Simpson K, et al. Trends in the incidence of renal replacement therapy for end-stage renal disease in Europe, 1990-1999. Nephrol Dial Transpl. 2003;18(9):1824–33.CrossRef
5.
Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002, 106(25):3143–3421.
6.
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 (London, England) 2010, 375(9731):2073–2081.
7.
Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351(13):1296–305.PubMedCrossRef
8.
Vervloet M, Cozzolino M. Vascular calcification in chronic kidney disease: different bricks in the wall? Kidney Int. 2017;91(4):808–17.PubMedCrossRef
9.
Merjanian R, Budoff M, Adler S, Berman N, Mehrotra R. Coronary artery, aortic wall, and valvular calcification in nondialyzed individuals with type 2 diabetes and renal disease. Kidney Int. 2003;64(1):263–71.PubMedCrossRef
10.
Zoppini G, Targher G, Negri C, Stoico V, Perrone F, Muggeo M, et al. Elevated serum uric acid concentrations independently predict cardiovascular mortality in type 2 diabetic patients. Diabetes Care. 2009;32(9):1716–20.PubMedPubMedCentralCrossRef
11.
Louwe MC, Lammers B, Frias MA, Foks AC, de Leeuw LR, Hildebrand RB, et al. Abca1 deficiency protects the heart against myocardial infarction-induced injury. Atherosclerosis. 2016;251:159–63.PubMedCrossRef
12.
Tanaka K, Hara S, Kushiyama A, Ubara Y, Yoshida Y, Mizuiri S, et al. Risk of macrovascular disease stratified by stage of chronic kidney disease in type 2 diabetic patients: critical level of the estimated glomerular filtration rate and the significance of hyperuricemia. Clin Exp Nephrol. 2011;15(3):391–7.PubMedCrossRef
13.
Tavil Y, Kaya MG, Oktar SO, Sen N, Okyay K, Yazici HU, et al. Uric acid level and its association with carotid intima-media thickness in patients with hypertension. Atherosclerosis. 2008;197(1):159–63.PubMedCrossRef
14.
Li L, Yang C, Zhao Y, Zeng X, Liu F, Fu P. Is hyperuricemia an independent risk factor for new-onset chronic kidney disease?: a systematic review and meta-analysis based on observational cohort studies. BMC Nephrol. 2014;15:122.PubMedPubMedCentralCrossRef
15.
Obermayr RP, Temml C, Gutjahr G, Knechtelsdorfer M, Oberbauer R, Klauser-Braun R. Elevated uric acid increases the risk for kidney disease. J Am Soc Nephrol. 2008;19(12):2407–13.PubMedPubMedCentralCrossRef
16.
Iseki K, Ikemiya Y, Inoue T, Iseki C, Kinjo K, Takishita S. Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort. Am J Kidney Dis. 2004;44(4):642–50.PubMedCrossRef
17.
Lv Q, Meng XF, He FF, Chen S, Su H, Xiong J, et al. High serum uric acid and increased risk of type 2 diabetes: a systemic review and meta-analysis of prospective cohort studies. PLoS One. 2013;8(2):e56864.PubMedPubMedCentralCrossRef
18.
Viazzi F, Leoncini G, Vercelli M, Deferrari G, Pontremoli R. Serum uric acid levels predict new-onset type 2 diabetes in hospitalized patients with primary hypertension: the MAGIC study. Diabetes Care. 2011;34(1):126–8.PubMedCrossRef
19.
Johnson RJ, Nakagawa T, Sanchez-Lozada LG, Shafiu M, Sundaram S, Le M, et al. Sugar, uric acid, and the etiology of diabetes and obesity. Diabetes. 2013;62(10):3307–15.PubMedPubMedCentralCrossRef
20.
Kang DH, Nakagawa T. Uric acid and chronic renal disease: possible implication of hyperuricemia on progression of renal disease. Semin Nephrol. 2005;25(1):43–9.PubMedCrossRef
21.
22.
Kim IY, Lee DW, Lee SB, Kwak IS. The role of uric acid in kidney fibrosis: experimental evidences for the causal relationship. Biomed Res Int. 2014;2014:638732.PubMedPubMedCentral
23.
24.
Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006;145(4):247–54.PubMedCrossRef
25.
Chuang SY, Chen JH, Yeh WT, Wu CC, Pan WH. Hyperuricemia and increased risk of ischemic heart disease in a large Chinese cohort. Int J Cardiol. 2012;154(3):316–21.PubMedCrossRef
26.
Rigalleau V, Lasseur C, Raffaitin C, Perlemoine C, Barthe N, Chauveau P, et al. Glucose control influences glomerular filtration rate and its prediction in diabetic subjects. Diabetes Care. 2006;29(7):1491–5.PubMedCrossRef
27.
Teo BW, Xu H, Wang D, Li J, Sinha AK, Shuter B, et al. GFR estimating equations in a multiethnic Asian population. Am J Kidney Dis. 2011;58(1):56–63.PubMedCrossRef
28.
Hsu CC, Hwang SJ, Wen CP, Chang HY, Chen T, Shiu RS, et al. High prevalence and low awareness of CKD in Taiwan: a study on the relationship between serum creatinine and awareness from a nationally representative survey. Am J Kidney Dis. 2006;48(5):727–38.PubMedCrossRef
29.
Hwang SJ, Yang WC, Lin MY, Mau LW, Chen HC. Taiwan Society of N: impact of the clinical conditions at dialysis initiation on mortality in incident haemodialysis patients: a national cohort study in Taiwan. Nephrol Dial Transpl. 2010;25(8):2616–24.CrossRef
30.
31.
Weiner DE, Tighiouart H, Elsayed EF, Griffith JL, Salem DN, Levey AS. Uric acid and incident kidney disease in the community. J Am Soc Nephrol. 2008;19(6):1204–11.PubMedPubMedCentralCrossRef
32.
Zhu P, Liu Y, Han L, Xu G, Ran JM. Serum uric acid is associated with incident chronic kidney disease in middle-aged populations: a meta-analysis of 15 cohort studies. PLoS One. 2014;9(6):e100801.PubMedPubMedCentralCrossRef
33.
Lee CL, Wang JS: Effects of hyperuricemia on incident renal replacement therapy and all-cause mortality among patients with chronic kidney disease stages 3-5: a retrospective cohort study. Sao Paulo Med J = Rev Paul Med 2019:137(6):523–529.
34.
35.
Weiner DE, Tighiouart H, Elsayed EF, Griffith JL, Salem DN, Levey AS, et al. The relationship between nontraditional risk factors and outcomes in individuals with stage 3 to 4 CKD. Am J Kidney Dis. 2008;51(2):212–23.PubMedPubMedCentralCrossRef
36.
Oh TR, Choi HS, Kim CS, Bae EH, Ma SK, Sung SA, et al. Hyperuricemia has increased the risk of progression of chronic kidney disease: propensity score matching analysis from the KNOW-CKD study. Sci Rep. 2019;9(1):6681.PubMedPubMedCentralCrossRef
37.
Johnson RJ, Bakris GL, Borghi C, Chonchol MB, Feldman D, Lanaspa MA, et al. Hyperuricemia, acute and chronic kidney disease, hypertension, and cardiovascular disease: report of a scientific workshop organized by the National Kidney Foundation. Am J Kidney Dis. 2018;71(6):851–65.PubMedPubMedCentralCrossRef
38.
Ohno I, Hosoya T, Gomi H, Ichida K, Okabe H, Hikita M. Serum uric acid and renal prognosis in patients with IgA nephropathy. Nephron. 2001;87(4):333–9.PubMedCrossRef
39.
Sanchez-Lozada LG, Tapia E, Santamaria J, Avila-Casado C, Soto V, Nepomuceno T, et al. Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats. Kidney Int. 2005;67(1):237–47.PubMedCrossRef
40.
Bellomo G, Venanzi S, Verdura C, Saronio P, Esposito A, Timio M. Association of uric acid with change in kidney function in healthy normotensive individuals. Am J Kidney Dis. 2010;56(2):264–72.PubMedCrossRef
41.
Kjellstrand CM, Cambell DC 2nd, von Hartitzsch B, Buselmeier TJ. Hyperuricemic acute renal failure. Arch Intern Med. 1974;133(3):349–59.PubMedCrossRef
42.
Johnson RJ, Kivlighn SD, Kim YG, Suga S, Fogo AB. Reappraisal of the pathogenesis and consequences of hyperuricemia in hypertension, cardiovascular disease, and renal disease. Am J Kidney Dis. 1999;33(2):225–34.PubMedCrossRef
43.
Abbott RD, Brand FN, Kannel WB, Castelli WP. Gout and coronary heart disease: the Framingham study. J Clin Epidemiol. 1988;41(3):237–42.PubMedCrossRef
44.
Choi HK, Curhan G. Independent impact of gout on mortality and risk for coronary heart disease. Circulation. 2007;116(8):894–900.PubMedCrossRef
45.
Cohen SD, Kimmel PL, Neff R, Agodoa L, Abbott KC. Association of incident gout and mortality in dialysis patients. J Am Soc Nephrol. 2008;19(11):2204–10.PubMedPubMedCentralCrossRef
46.
Singh JA, Ramachandaran R, Yu S, Yang S, Xie F, Yun H, et al. Is gout a risk equivalent to diabetes for stroke and myocardial infarction? A retrospective claims database study. Arthritis Res Ther. 2017;19(1):228.PubMedPubMedCentralCrossRef
47.
Kim SY, Guevara JP, Kim KM, Choi HK, Heitjan DF, Albert DA. Hyperuricemia and risk of stroke: a systematic review and meta-analysis. Arthritis Rheum. 2009;61(7):885–92.PubMedPubMedCentralCrossRef
48.
Kim SY, Guevara JP, Kim KM, Choi HK, Heitjan DF, Albert DA. Hyperuricemia and coronary heart disease: a systematic review and meta-analysis. Arthritis Care Res (Hoboken). 2010;62(2):170–80.
49.
Choi YJ, Yoon Y, Lee KY, Hien TT, Kang KW, Kim KC, et al. Uric acid induces endothelial dysfunction by vascular insulin resistance associated with the impairment of nitric oxide synthesis. FASEB J. 2014;28(7):3197–204.PubMedCrossRef
50.
Gersch C, Palii SP, Kim KM, Angerhofer A, Johnson RJ, Henderson GN. Inactivation of nitric oxide by uric acid. Nucleosides Nucleotides Nucleic Acids. 2008;27(8):967–78.PubMedPubMedCentralCrossRef
51.
Yu MA, Sanchez-Lozada LG, Johnson RJ, Kang DH. Oxidative stress with an activation of the renin-angiotensin system in human vascular endothelial cells as a novel mechanism of uric acid-induced endothelial dysfunction. J Hypertens. 2010;28(6):1234–42.PubMedCrossRef
52.
Kanellis J, Kang DH. Uric acid as a mediator of endothelial dysfunction, inflammation, and vascular disease. Semin Nephrol. 2005;25(1):39–42.PubMedCrossRef
53.
Sanchez-Lozada LG, Lanaspa MA, Cristobal-Garcia M, Garcia-Arroyo F, Soto V, Cruz-Robles D, et al. Uric acid-induced endothelial dysfunction is associated with mitochondrial alterations and decreased intracellular ATP concentrations. Nephron Exp Nephrol. 2012;121(3–4):e71–8.PubMedCrossRef
54.
Feig DI, Nakagawa T, Karumanchi SA, Oliver WJ, Kang DH, Finch J, et al. Hypothesis: uric acid, nephron number, and the pathogenesis of essential hypertension. Kidney Int. 2004;66(1):281–7.PubMedCrossRef
55.
Mazzali M, Hughes J, Kim YG, Jefferson JA, Kang DH, Gordon KL, et al. Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension. 2001;38(5):1101–6.PubMedCrossRef
56.
Valle M, Martos R, Canete MD, Valle R, van Donkelaar EL, Bermudo F, et al. Association of serum uric acid levels to inflammation biomarkers and endothelial dysfunction in obese prepubertal children. Pediatr Diabetes. 2015;16(6):441–7.PubMedCrossRef
57.
Kanellis J, Watanabe S, Li JH, Kang DH, Li P, Nakagawa T, et al. Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen-activated protein kinase and cyclooxygenase-2. Hypertension. 2003;41(6):1287–93.PubMedCrossRef
58.
Rao GN, Corson MA, Berk BC. Uric acid stimulates vascular smooth muscle cell proliferation by increasing platelet-derived growth factor A-chain expression. J Biol Chem. 1991;266(13):8604–8.PubMedCrossRef
59.
Corry DB, Eslami P, Yamamoto K, Nyby MD, Makino H, Tuck ML. Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin-angiotensin system. J Hypertens. 2008;26(2):269–75.PubMedCrossRef
60.
Chao HH, Liu JC, Lin JW, Chen CH, Wu CH, Cheng TH. Uric acid stimulates endothelin-1 gene expression associated with NADPH oxidase in human aortic smooth muscle cells. Acta Pharmacol Sin. 2008;29(11):1301–12.PubMedCrossRef
61.
Buckland J. Crystal arthropathies: the NET is closing in on inflammation in gout. Nat Rev Rheumatol. 2014;10(6):319.PubMedCrossRef
62.
Dalbeth N, Haskard DO. Mechanisms of inflammation in gout. Rheumatology (Oxford). 2005;44(9):1090–6.CrossRef
63.
64.
Gislason GH, Rasmussen JN, Abildstrom SZ, Schramm TK, Hansen ML, Fosbol EL, et al. Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure. Arch Intern Med. 2009;169(2):141–9.PubMedCrossRef
65.
Lai KM, Chen TL, Chang CC, Chen HH, Lee YW. Association between NSAID use and mortality risk in patients with end-stage renal disease: a population-based cohort study. Clin Epidemiol. 2019;11:429–41.PubMedPubMedCentralCrossRef
66.
Jo HA, Kim DK, Park S, Kim Y, Han SS, Yang BR, Choi SH, Kim MS, Lee J, Lee H et al: Cardiovascular risk of nonsteroidal anti-inflammatory drugs in dialysis patients: a nationwide population-based study. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 2020.
67.
Doehner W, Schoene N, Rauchhaus M, Leyva-Leon F, Pavitt DV, Reaveley DA, et al. Effects of xanthine oxidase inhibition with allopurinol on endothelial function and peripheral blood flow in hyperuricemic patients with chronic heart failure: results from 2 placebo-controlled studies. Circulation. 2002;105(22):2619–24.PubMedCrossRef
68.
Tsai MH, Hsu CY, Lin MY, Yen MF, Chen HH, Chiu YH, et al. Incidence, prevalence, and duration of chronic kidney disease in Taiwan: results from a community-based screening program of 106,094 individuals. Nephron. 2018;140(3):175–84.PubMedCrossRef
69.
Chang YK, Liu JS, Hsu YH, Tarng DC, Hsu CC. Increased risk of end-stage renal disease (ESRD) requiring chronic Dialysis is associated with use of nonsteroidal anti-inflammatory drugs (NSAIDs): Nationwide case-crossover study. Medicine (Baltimore). 2015;94(38):e1362.CrossRef
70.
71.
Bartakova V, Kuricova K, Pacal L, Nova Z, Dvorakova V, Svrckova M, et al. Hyperuricemia contributes to the faster progression of diabetic kidney disease in type 2 diabetes mellitus. J Diabetes Complicat. 2016;30(7):1300–7.CrossRef
72.
Chang YH, Lei CC, Lin KC, Chang DM, Hsieh CH, Lee YJ. Serum uric acid level as an indicator for CKD regression and progression in patients with type 2 diabetes mellitus-a 4.6-year cohort study. Diabetes Metab Res Rev. 2016;32(6):557–64.PubMedCrossRef
73.
Hisatome I, Kuwabara M. Hyperuricemia plays pivotal role in progression of kidney disease. Circ J. 2016;80(8):1710–1.PubMedCrossRef
74.
Pichler R, Afkarian M, Dieter BP, Tuttle KR. Immunity and inflammation in diabetic kidney disease: translating mechanisms to biomarkers and treatment targets. Am J Physiol Renal Physiol. 2017;312(4):F716–f731.PubMedCrossRef
75.
Hojs R, Ekart R, Bevc S, Hojs N. Markers of inflammation and oxidative stress in the development and progression of renal disease in diabetic patients. Nephron. 2016;133(3):159–62.PubMedCrossRef
76.
Yan D, Wang J, Jiang F, Zhang R, Sun X, Wang T, et al. Association between serum uric acid related genetic loci and diabetic kidney disease in the Chinese type 2 diabetes patients. J Diabetes Complicat. 2016;30(5):798–802.CrossRef
77.
Mukri MNA, Kong WY, Mustafar R, Shaharir SS, Shah SA, Abdul Gafor AH, et al. Role of febuxostat in retarding progression of diabetic kidney disease with asymptomatic hyperuricemia: a 6-months open-label, randomized controlled trial. EXCLI J. 2018;17:563–75.PubMedPubMedCentral
78.
Momeni A, Shahidi S, Seirafian S, Taheri S, Kheiri S. Effect of allopurinol in decreasing proteinuria in type 2 diabetic patients. Iran J Kidney Dis. 2010;4(2):128–32.PubMed
79.
Metadata
Title
Hyperuricemia and diabetes mellitus when occurred together have higher risks than alone on all-cause mortality and end-stage renal disease in patients with chronic kidney disease
Authors
Cheng-Hung Li
Chia-Lin Lee
Yu-Cheng Hsieh
Cheng-Hsu Chen
Ming-Ju Wu
Shang-Feng Tsai
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2022
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-022-02755-1

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