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Gout and the risk of advanced chronic kidney disease in the UK health system: a national cohort study
  1. Austin G Stack1,
  2. Michelle Elizabeth Johnson2,
  3. Betina Blak3,
  4. Alyssa Klein4,
  5. Lewis Carpenter2,
  6. Robert Morlock5,
  7. Andrew R Maguire2,
  8. Victoria L Parsons2
  1. 1Graduate Entry Medical School & Health Research Institute, University of Limerick, Limerick, Ireland
  2. 2OXON Epidemiology, London, UK
  3. 3AstraZeneca, Luton, UK
  4. 4AstraZeneca, Gaithersburg, Maryland, USA
  5. 5YourCareChoice, Ann Arbor, Michigan, USA
  1. Correspondence to Dr Austin G Stack; austin.stack{at}ul.ie

Abstract

Objective Evaluate the association between gout and risk of advanced chronic kidney disease (CKD).

Design Retrospective matched cohort study.

Setting UK Clinical Practice Research Datalink.

Participants The analysis included data for 68 897 patients with gout and 554 964 matched patients without gout. Patients were aged ≥18 years, registered at UK practices, had ≥12 months of clinical data and had data linked with Hospital Episode Statistics. Patients were excluded for history of advanced CKD, juvenile gout, cancer, HIV, tumour lysis syndrome, Lesch-Nyhan syndrome or familial Mediterranean fever.

Primary and secondary outcome measures Advanced CKD was defined as first occurrence of: (1) dialysis, kidney transplant, diagnosis of end-stage kidney disease (ESKD) or stage 5 CKD (diagnostic codes in Read system or International Classification of Diseases, Tenth Revision); (2) estimated glomerular filtration rate (eGFR) <10 mL/min/1.73 m²; (3) doubling of serum creatinine from baseline and (4) death associated with CKD.

Results Advanced CKD incidence was higher for patients with gout (8.54 per 1000 patient-years; 95% CI 8.26 to 8.83) versus without gout (4.08; 95% CI 4.00 to 4.16). Gout was associated with higher advanced CKD risk in both unadjusted analysis (HR, 2.00; 95% CI 1.92 to 2.07) and after adjustment (HR, 1.29; 95% CI 1.23 to 1.35). Association was strongest for ESKD (HR, 2.13; 95% CI 1.73 to 2.61) and was present for eGFR <10 mL/min/1.73 m² (HR, 1.45; 95% CI 1.30 to 1.61) and serum creatinine doubling (HR, 1.13; 95% CI 1.08 to 1.19) but not CKD-associated death (HR, 1.14; 95% CI 0.99 to 1.31). Association of gout with advanced CKD was replicated in propensity-score matched analysis (HR, 1.23; 95% CI 1.17 to 1.29) and analysis limited to patients with incident gout (HR, 1.28; 95% CI 1.22 to 1.35).

Conclusions Gout is associated with elevated risk of CKD progression. Future studies should investigate whether controlling gout is protective and reduces CKD risk.

  • chronic renal failure
  • dialysis
  • end-stage renal failure
  • epidemiology

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Presented at The results of this study were presented at the Annual Scientific Meetings of the American College of Rheumatology in 2016 and the European Renal Association & European Dialysis and Transplantation (ERA-EDTA) Meeting in 2017.

  • Contributors AGS, RM and BB conceived the study protocol. AGS, BB, MEJ, AK, RM and ARM coordinated the execution of the study. VLP, MEJ and LC performed the statistical analyses. AGS, VLP and MEJ drafted the manuscript. All authors contributed to the interpretation of results, further drafts of the manuscript and approved the final manuscript.

  • Funding statement This study was funded by AstraZeneca. BB, AK, and RM were employed by AstraZeneca the time of the study and were involved in the design of the study, interpretation of the results, the preparation, review, and approval of the manuscript and the decision to publish.

  • Competing interests AGS received funding from AstraZeneca to design the study protocol and provide scientific expertise. VLP, MEJ, LC and ARM were employed by OXON Epidemiology Ltd at the time of the study, which has received funding from AstraZeneca to conduct the study and develop the manuscript. BB, AK and RM were employed by AstraZeneca at the time of the study, which funded the study.

  • Patient consent for publication Not required.

  • Ethics approval The protocol for this research was approved by the Independent Scientific Advisory Committee (ISAC) of the Medicines and Healthcare Products Regulatory Agency (protocol number 15_009RMn). The CPRD has been granted generic ethics approval for observational studies that make use of only anonymised data and linked anonymised NHS healthcare data (Multiple Research Ethics Committee ref. 05/MRE04/87).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement MEJ had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All source data were obtained from the Clinical Practice Research Datalink (CPRD), linked with data from Hospital Episodes Statistics database and Office of National Statistics. These data sources are made available for scientific and medical research after submission of a study protocol to be reviewed and approved by the CPRD Independent Scientific Advisory Committee (ISAC). Owing to ethical restrictions, the data used in this analysis are not publicly available, in line with the data privacy rules set up by CPRD/ISAC.

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