Restricted accessResearch articleFirst published online 2023-1
Association between serum uric acid level and systemic lupus erythematosus kidney outcome: An observational study in Southern Chinese population and a meta-analysis
The study aimed to explore the effect of serum uric acid (SUA) level on the progression of kidney function in systemic lupus erythematosus (SLE) patients
Methods
A total of 123 biopsy-proven lupus nephritis (LN) patients were included in this retrospective observational study. Cox proportional hazard regression analyses as well as restricted cubic spline analyses were performed to identify predictors of renal outcome in LN patients. We also performed a systematic review and meta-analysis for SUA and overall kidney outcomes in SLE patients.
Results
Based on the laboratory tests at renal biopsy, 72 (58.5%) of the 123 patients had hyperuricemia. The median (IQR) follow-up duration was 3.67 years (1.79–6.63 years), and a total of 110 (89.4%) patients experienced progression of LN. Increased serum uric acid level, whether analyzed as continuous or categorical variable, was associated with higher risk of LN progression in Cox proportional hazard regression model (hazard ratio [HR]: 1.003, 95% confidence interval [CI]: 1.001–1.005; HR: 1.780, 95% CI: 1.201–2.639, respectively). This relationship maintained in women (HR: 1.947, 95% CI: 1.234–3.074) but not men (HR: 2.189, 95% CI: 0.802–5.977). The meta-analysis showed a similar result that both continuous and categorical SUA were positively associated with the risk of kidney function progression in LN (weighted mean difference [WMD]: 1.73, 95% CI: 0.97–2.49; odds ratio [OR]: 1.55, 95% CI: 1.20–2.01, respectively).
Conclusions
Our study found overall and especially in women that higher SUA in LN patients were associated with increased risk of renal progression. Meta-analysis yielded consistent results. Future studies are required to establish if uric acid can be used as a biomarker for risk assessment and/or as a novel therapeutic target in SLE.
BernatskySBoivinJFJosephL, et al.Mortality in systemic lupus erythematosus. Arthritis Rheum2006; 54: 2550–2557. DOI: 10.1002/art.21955.
2.
KasitanonNMagderLSPetriM. Predictors of survival in systemic lupus erythematosus. Medicine (Baltimore)2006; 85: 147–156. DOI: 10.1097/01.md.0000224709.70133.f7.
3.
BertsiasGKTektonidouMAmouraZ, et al.Joint European league against rheumatism and European renal association-European dialysis and transplant association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis2012; 71: 1771–1782. DOI: 10.1136/annrheumdis-2012-201940.
4.
HahnBHMcMahonMAWilkinsonA, et al.American college of rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken)2012; 64: 797–808. DOI: 10.1002/acr.21664.
5.
FrochtALeekJCRobbinsDL. Gout and hyperuricaemia in systemic lupus erythematosus. Br J Rheumatol1987; 26: 303–306. DOI: 10.1093/rheumatology/26.4.303.
6.
OhTRChoiHSKimCS, et al.Serum uric acid is associated with renal prognosis of lupus nephritis in women but not in men. J Clin Med2020; 9. DOI: 10.3390/jcm9030773.
7.
ParkDJChoiSEXuH, et al.Uric acid as a risk factor for progression to chronic kidney disease in patients with lupus nephritis: results from the KORNET registry. Clin Exp Rheumatol2021; 39: 947–954.
8.
KimSYGuevaraJPKimKM, et al.Hyperuricemia and coronary heart disease: a systematic review and meta-analysis. Arthritis Care Res (Hoboken)2010; 62: 170–180. DOI: 10.1002/acr.20065.
9.
LiLYangCZhaoY, et al.Is hyperuricemia an independent risk factor for new-onset chronic kidney disease?: a systematic review and meta-analysis based on observational cohort studies. BMC Nephrol2014; 15: DOI: 10.1186/1471-2369-15-122.
10.
CappuccioFPStrazzulloPFarinaroE, et al.Uric acid metabolism and tubular sodium handling: results from a population-based study. Jama1993; 270: 354–359.
11.
Elera-FitzcarraldCReátegui-SokolovaCGamboa-CardenasRV, et al.Serum uric acid is associated with damage in patients with systemic lupus erythematosus. Lupus Sci Med2020; 7: e000366. DOI: 10.1136/lupus-2019-000366.
12.
KhannaDFitzgeraldJDKhannaPP, et al.2012American college of rheumatology guidelines for management of gout. part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken)2012; 64: 1431–1446. DOI: 10.1002/acr.21772.
13.
StampLDalbethN. Urate-lowering therapy for asymptomatic hyperuricaemia: a need for caution. Semin Arthritis Rheum2017; 46: 457–464. DOI: 10.1016/j.semarthrit.2016.07.015.
14.
HochbergMC. Updating the American college of rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum1997; 40: 1725. DOI: 10.1002/art.1780400928.
15.
GladmanDDGoldsmithCHUrowitzMB, et al.The systemic lupus international collaborating clinics/American college of rheumatology (SLICC/ACR) damage index for systemic lupus erythematosus international comparison. J Rheumatol2000; 27: 373–376.
WeeningJJD’AgatiVDSchwartzMM, et al.The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol2004; 15: 241–250. DOI: 10.1097/01.asn.0000108969.21691.5d.
18.
LeveyASStevensLASchmidCH, et al.A new equation to estimate glomerular filtration rate. Ann Intern Med2009; 150: 604–612. DOI: 10.7326/0003-4819-150-9-200905050-00006.
19.
TherneauTMGrambschPM. The Cox Model: Modeling Survival Data—Extending the Cox Model, Berlin, Germany,: Springer; 2000.
20.
TeamRC. The R Project for Statistical Computing. Vienna, Austria: R Foundation, 2013.
21.
PageMJMcKenzieJEBossuytPM, et al.The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ (Clinical research ed)2021; 372: DOI: 10.1136/bmj.n71.
22.
EggerMDavey SmithGSchneiderM, et al.Bias in meta-analysis detected by a simple, graphical test. BMJ (Clinical research ed)1997; 315: 629–634. DOI: 10.1136/bmj.315.7109.629.
23.
CumpstonMLiTPageM, et al.Updated guidance for trusted systematic reviews: a new edition of the cochrane handbook for systematic reviews of interventions. Cochrane database Syst Rev2019; 10: ED000142. DOI: 10.1002/14651858.Ed000142.
24.
StangACritical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol2010; 25: 603–605. DOI: 10.1007/s10654-010-9491-z.
25.
LiuHPengLMaJ, et al.Low expression of estrogen receptor β in renal tubular epithelial cells may cause hyperuricemia in premenopausal patients with systemic lupus erythematosus. Lupus2021; 30: 560–567. DOI: 10.1177/0961203320984231.
26.
XieTChenMTangX, et al.Hyperuricemia is an independent risk factor for renal pathological damage and poor prognosis in lupus nephritis patients. Zhong Nan Da Xue Xue Bao Yi Xue Ban2016; 41: 1052–1057. DOI: 10.11817/j.issn.1672-7347.2016.10.007.
27.
CalichALBorbaEFUgolini-LopesMR, et al.Serum uric acid levels are associated with lupus nephritis in patients with normal renal function. Clin Rheumatol2018; 37: 1223–1228. DOI: 10.1007/s10067-018-3991-8.
28.
ChengYYangXZhangX, et al.Analysis of expression levels of IL-17 and IL-34 and influencing factors for prognosis in patients with lupus nephritis. Exp Ther Med2019; 17: 2279–2283. DOI: 10.3892/etm.2019.7168.
29.
ElnadyBAlmalkiAAbdel-FattahMM, et al.Serum uric acid as a sensitive concordant marker with lupus nephritis and new onset of renal damage: a prospective cohort study. Clin Rheumatol2021; 40: 1827–1834. DOI: 10.1007/s10067-020-05473-x.
30.
HafezEAHassanSAETeamaMAM, et al.Serum uric acid as a predictor for nephritis in Egyptian patients with systemic lupus erythematosus. Lupus2021; 30: 378–384. DOI: 10.1177/0961203320979042.
31.
LiuSGongYRenH, et al.The prevalence, subtypes and associated factors of hyperuricemia in lupus nephritis patients at chronic kidney disease stages 1–3. Oncotarget2017; 8: 57099–57108. DOI: 10.18632/oncotarget.19051.
32.
Reátegui-SokolovaCUgarte-GilMFGamboa-CárdenasRV, et al.Serum uric acid levels contribute to new renal damage in systemic lupus erythematosus patients. Clin Rheumatol2017; 36: 845–852. DOI: 10.1007/s10067-017-3538-4.
33.
Ugolini-LopesMRGavinierSSLeonE, et al.Is serum uric acid a predictor of long-term renal outcome in lupus nephritis?Clin Rheumatol2019; 38: 2777–2783. DOI: 10.1007/s10067-019-04620-3.
34.
YangZLiangYXiW, et al.Association of serum uric acid with lupus nephritis in systemic lupus erythematosus. Rheumatol Int2011; 31: 743–748. DOI: 10.1007/s00296-010-1373-x.
35.
SayginDHighlandKTonelliA. Microvascular involvement in systemic sclerosis and systemic lupus erythematosus. Microcirculation (New York, NY, USA): 2019; 26: e12440. DOI: 10.1111/micc.12440.
36.
VaziriNFreelRHatchM. Effect of chronic experimental renal insufficiency on urate metabolism. J Am Soc Nephrol : JASN1995; 6: 1313–1317. DOI: 10.1681/asn.V641313.
37.
CorryDEslamiPYamamotoK, et al.Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin-angiotensin system. J Hypertens2008; 26: 269–275. DOI: 10.1097/HJH.0b013e3282f240bf.
38.
Sánchez-LozadaLTapiaESantamaríaJ, et al.Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats. Kidney Int2005; 67: 237–247. DOI: 10.1111/j.1523-1755.2005.00074.x.
39.
JalalDRivardCJohnsonR, et al.Serum uric acid levels predict the development of albuminuria over 6 years in patients with type 1 diabetes: findings from the coronary artery calcification in type 1 diabetes study. Nephrol Dial Transplant: 2010; 25: 1865–1869. DOI: 10.1093/ndt/gfp740.
40.
KangDHNakagawaTFengL, et al.A role for uric acid in the progression of renal disease. J Am Soc Nephrol2002; 13: 2888–2897. DOI: 10.1097/01.asn.0000034910.58454.fd.
41.
ZhaoDZhouZShenC, et al.Rural and urban differences in patient experience in China: a coarsened exact matching study from the perspective of residents. BMC Health Serv Res2021; 21: 330. DOI: 10.1186/s12913-021-06328-0.
42.
YangYQinXLiY, et al.Relationship between serum uric acid and mortality risk in hemodialysis patients: a multicenter prospective cohort study. Am J Nephrol2020; 51: 823–832. DOI: 10.1159/000509258.
43.
SiuYPLeungKTTongMK, et al.Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. Am J Kidney Dis2006; 47: 51–59. DOI: 10.1053/j.ajkd.2005.10.006.
44.
LiangXLiuXLiD, et al.Effectiveness of urate-lowering therapy for renal function in patients with chronic kidney disease: a meta-analysis of randomized clinical trials. Front Pharmacol2022; 13: 798150. DOI: 10.3389/fphar.2022.798150.
45.
JalalDIChoncholMChenW, et al.Uric acid as a target of therapy in CKD. Am J Kidney Dis2013; 61: 134–146. 2012/10/13. DOI: 10.1053/j.ajkd.2012.07.021.
46.
JalalDIChertowGM. Urate lowering with combination therapy in CKD: reason for optimism or Einstein’s definition of insanity?Am J Kidney Dis2021; 77: 478–480. DOI: 10.1053/j.ajkd.2020.11.007.
47.
BoseBBadveSVHiremathSS, et al.Effects of uric acid-lowering therapy on renal outcomes: a systematic review and meta-analysis. Nephrol Dial Transpl2014; 29: 406–413. DOI: 10.1093/ndt/gft378.
48.
BadveSVPascoeEMTikuA, et al.Effects of allopurinol on the progression of chronic kidney disease. N Engl J Med2020; 382: 2504–2513. DOI: 10.1056/NEJMoa1915833.
49.
DoriaAGaleckiASpinoC, et al.Serum urate lowering with allopurinol and kidney function in type 1 diabetes. New Engl J Med2020; 382: 2493–2503. DOI: 10.1056/NEJMoa1916624.
50.
Pilemann-LybergSHansenTWTofteN, et al.Uric acid is an independent risk factor for decline in kidney function, cardiovascular events, and mortality in patients with type 1 diabetes. Diabetes Care2019; 42: 1088–1094. DOI: 10.2337/dc18-2173.
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