Risk of chronic kidney disease in patients with gout and the impact of urate lowering therapy: a population-based cohort study

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Abstract

Background

An association between gout and renal disease is well-recognised but few studies have examined whether gout is a risk factor for subsequent chronic kidney disease (CKD). Additionally, the impact of urate-lowering therapy (ULT) on development of CKD in gout is unclear. The objective of this study was to quantify the risk of CKD stage ≥ 3 in people with gout and the impact of ULT.

Methods

This was a retrospective cohort study using data from the Clinical Practice Research Datalink (CPRD). Patients with incident gout were identified from general practice medical records between 1998 and 2016 and randomly matched 1:1 to patients without a diagnosis of gout based on age, gender, available follow-up time and practice. Primary outcome was development of CKD stage ≥ 3 based on estimated glomerular filtration rate (eGFR) or recorded diagnosis. Absolute rates (ARs) and adjusted hazard ratios (HRs) were calculated using Cox regression models. Risk of developing CKD was assessed among those prescribed ULT within 1 and 3 years of gout diagnosis.

Results

Patients with incident gout ( n = 41,446) were matched to patients without gout. Development of CKD stage ≥ 3 was greater in the exposed group than in the unexposed group (AR 28.6 versus 15.8 per 10,000 person-years). Gout was associated with an increased risk of incident CKD (adjusted HR 1.78 95% CI 1.70 to 1.85). Those exposed to ULT had a greater risk of incident CKD, but following adjustment this was attenuated to non-significance in all analyses (except on 3-year analysis of women (adjusted HR 1.31 95% CI 1.09 to 1.59)).

Conclusions

This study has demonstrated gout to be a risk factor for incident CKD stage ≥ 3. Further research examining the mechanisms by which gout may increase risk of CKD and whether optimal use of ULT can reduce the risk or progression of CKD in gout is suggested.

Electronic supplementary material

The online version of this article (10.1186/s13075-018-1746-1) contains supplementary material, which is available to authorized users.

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Most cited references 30

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The NLRP3 inflammasome promotes renal inflammation and contributes to CKD.

Akosua Vilaysane, Justin Chun, Mark Seamone … (2010)

Inflammation significantly contributes to the progression of chronic kidney disease (CKD). Inflammasome-dependent cytokines, such as IL-1β and IL-18, play a role in CKD, but their regulation during renal injury is unknown. Here, we analyzed the processing of caspase-1, IL-1β, and IL-18 after unilateral ureteral obstruction (UUO) in mice, which suggested activation of the Nlrp3 inflammasome during renal injury. Compared with wild-type mice, Nlrp3(-/-) mice had less tubular injury, inflammation, and fibrosis after UUO, associated with a reduction in caspase-1 activation and maturation of IL-1β and IL-18; these data confirm that the Nlrp3 inflammasome upregulates these cytokines in the kidney during injury. Bone marrow chimeras revealed that Nlrp3 mediates the injurious/inflammatory processes in both hematopoietic and nonhematopoietic cellular compartments. In tissue from human renal biopsies, a wide variety of nondiabetic kidney diseases exhibited increased expression of NLRP3 mRNA, which correlated with renal function. Taken together, these results strongly support a role for NLRP3 in renal injury and identify the inflammasome as a possible therapeutic target in the treatment of patients with progressive CKD.

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Rising burden of gout in the UK but continuing suboptimal management: a nationwide population study

Chang-Fu Kuo, Matthew J Grainge, Christian David Mallen … (2014)

Objectives To describe trends in the epidemiology of gout and patterns of urate-lowering treatment (ULT) in the UK general population from 1997 to 2012. Methods We used the Clinical Practice Research Datalink to estimate the prevalence and incidence of gout for each calendar year from 1997 to 2012. We also investigated the pattern of gout management for both prevalent and incident gout patients. Results In 2012, the prevalence of gout was 2.49% (95% CI 2.48% to 2.51%) and the incidence was 1.77 (95% CI 1.73 to 1.81) per 1000 person-years. Prevalence and incidence both were significantly higher in 2012 than in 1997, with a 63.9% increase in prevalence and 29.6% increase in incidence over this period. Regions with highest prevalence and incidence were the North East and Wales. Among prevalent gout patients in 2012, only 48.48% (95% CI 48.08% to 48.89%) were being consulted specifically for gout or treated with ULT and of these 37.63% (95% CI 37.28% to 38.99%) received ULT. In addition, only 18.6% (95% CI 17.6% to 19.6%) of incident gout patients received ULT within 6 months and 27.3% (95% CI 26.1% to 28.5%) within 12 months of diagnosis. The management of prevalent and incident gout patients remained essentially the same during the study period, although the percentage of adherent patients improved from 28.28% (95% CI 27.33% to 29.26%) in 1997 to 39.66% (95% CI 39.11% to 40.22%) in 2012. Conclusions In recent years, both the prevalence and incidence of gout have increased significantly in the UK. Suboptimal use of ULT has not changed between 1997 and 2012. Patient adherence has improved during the study period, but it remains poor.

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Hyperuricemia, Acute and Chronic Kidney Disease, Hypertension, and Cardiovascular Disease: Report of a Scientific Workshop Organized by the National Kidney Foundation.

Richard J. Johnson, George L. Bakris, Claudio Borghi … (2018)

Urate is a cause of gout, kidney stones, and acute kidney injury from tumor lysis syndrome, but its relationship to kidney disease, cardiovascular disease, and diabetes remains controversial. A scientific workshop organized by the National Kidney Foundation was held in September 2016 to review current evidence. Cell culture studies and animal models suggest that elevated serum urate concentrations can contribute to kidney disease, hypertension, and metabolic syndrome. Epidemiologic evidence also supports elevated serum urate concentrations as a risk factor for the development of kidney disease, hypertension, and diabetes, but differences in methodologies and inpacts on serum urate concentrations by even subtle changes in kidney function render conclusions uncertain. Mendelian randomization studies generally do not support a causal role of serum urate in kidney disease, hypertension, or diabetes, although interpretation is complicated by nonhomogeneous populations, a failure to consider environmental interactions, and a lack of understanding of how the genetic polymorphisms affect biological mechanisms related to urate. Although several small clinical trials suggest benefits of urate-lowering therapies on kidney function, blood pressure, and insulin resistance, others have been negative, with many trials having design limitations and insufficient power. Thus, whether uric acid has a causal role in kidney and cardiovascular diseases requires further study.

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Author and article information

Contributors

Matthew Roughley:

ORCID: http://orcid.org/0000-0001-5095-4150

mattjroughley@gmail.com

Alyshah Abdul Sultan: a.abdul.sultan@keele.ac.uk

Lorna Clarson: l.clarson@keele.ac.uk

Sara Muller: s.muller@keele.ac.uk

Rebecca Whittle: r.l.whittle@keele.ac.uk

John Belcher: j.belcher@keele.ac.uk

Christian D. Mallen: c.d.mallen@keele.ac.uk

Edward Roddy: e.roddy@keele.ac.uk

Journal

Journal ID (nlm-ta): Arthritis Res Ther

Journal ID (iso-abbrev): Arthritis Res. Ther

Title: Arthritis Research & Therapy

Publisher: BioMed Central (London )

ISSN (Print): 1478-6354

ISSN (Electronic): 1478-6362

Publication date (Electronic): 30 October 2018

Publication date PMC-release: 30 October 2018

Publication date (Print): 2018

Volume: 20

Electronic Location Identifier: 243

Affiliations

[1 ]ISNI 0000 0004 0426 7183, GRID grid.450709.f, East London NHS Foundation Trust, Trust Headquarters, ; 9 Alie Street, London, E1 8DE UK

[2 ]ISNI 0000 0004 0415 6205, GRID grid.9757.c, Research Institute for Primary Care and Health Sciences, , Keele University, ; Keele, Staffordshire ST5 5BG UK

[3 ]ISNI 0000 0004 0415 6205, GRID grid.9757.c, School of Computing and Mathematics, , Keele University, ; Keele, Staffordshire ST5 5BG UK

[4 ]ISNI 0000 0004 0417 8199, GRID grid.413807.9, Haywood Academic Rheumatology Centre, Midland Partnership NHS Foundation Trust, Haywood Hospital, ; Burslem, Staffordshire ST6 7AG UK

Author information

Matthew Roughley http://orcid.org/0000-0001-5095-4150

Article

Publisher ID: 1746

DOI: 10.1186/s13075-018-1746-1

PMC ID: 6235219

PubMed ID: 30376864

SO-VID: e678bf4d-9feb-4c3b-b6ed-8c98b634841a

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 20 June 2018

Date accepted : 15 October 2018

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001308, Jean Shanks Foundation;

Funded by: FundRef http://dx.doi.org/10.13039/501100000272, National Institute for Health Research;

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ScienceOpen disciplines: Orthopedics

Keywords: gout,chronic kidney disease,urate-lowering therapy,cohort

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ScienceOpen disciplines: Orthopedics

Keywords: gout, chronic kidney disease, urate-lowering therapy, cohort

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Risk of chronic kidney disease in patients with gout and the impact of urate lowering therapy: a population-based cohort study

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Most cited references 30

The NLRP3 inflammasome promotes renal inflammation and contributes to CKD.

Rising burden of gout in the UK but continuing suboptimal management: a nationwide population study

Hyperuricemia, Acute and Chronic Kidney Disease, Hypertension, and Cardiovascular Disease: Report of a Scientific Workshop Organized by the National Kidney Foundation.

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Cited by 22

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