Gout & Uric Acid Research in Progress

Gout & Uric Acid Research in Progress

These are the gout studies, uric acid investigations, and related resources that I am currently working on.

If you want me to prioritize any articles, let me know in the gout forum. Or in the feedback form below. Also let me know if you want to collaborate on any research.

GoutPal Research Ideas

These are sources of information that look interesting and useful. So when I get time, I will publish a review here.

See 2020 ACR Guideline below
This is the most important study that I need to update all gout sufferer plans. So I will do these in groups as they relate to specific recommendations. Especially conditional ones that require patient decision-making. Starting with the first 30 of 118:
1. Chen-Xu M, Yokose C, Rai SK, Pillinger MH, Choi HK. Contemporary prevalence of gout and hyperuricemia in the United States and decadal trends: the National Health and Nutrition Examination Survey, 2007–2016. Arthritis Rheumatol 2019;71:991–9.
2. Rashid N, Coburn BW, Wu YL, Cheetham TC, Curtis JR, Saag KG, et al. Modifiable factors associated with allopurinol adherence and outcomes among patients with gout in an integrated healthcare system. J Rheumatol 2015;42:504–12.
3. Sarawate CA, Brewer KK, Yang W, Patel PA, Schumacher HR, Saag KG, et al. Gout medication treatment patterns and adherence to standards of care from a managed care perspective. Mayo Clin Proc 2006;81:925–34.
4. Singh JA, Hodges JS, Toscano JP, Asch SM. Quality of care for gout in the US needs improvement. Arthritis Rheum 2007;57: 822–9.
5. Khanna D, Fitzgerald JD, Khanna PP, Bae S, Singh MK, Neogi T, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1. Systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken) 2012;64:1431–46.
6. Khanna D, Khanna PP, Fitzgerald JD, Singh MK, Bae S, Neogi T, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 2. Therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthritis Care Res (Hoboken) 2012;64:1447–61.
7. Romeijnders AC, Gorter KJ. Summary of the Dutch College of General Practitioners’ “Gout” Standard. Ned Tijdschr Geneeskd 2002;146:309–13. In Dutch.
8. Zhang W, Doherty M, Bardin T, Pascual E, Barskova V, Conaghan P, et al. EULAR evidence based recommendations for gout. Part II. Management: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2006;65:1312–24.
9. Jordan KM, Cameron JS, Snaith M, Zhang W, Doherty M, Seckl J, et al. British Society for Rheumatology and British Health Professionals in Rheumatology guideline for the management of gout. Rheumatology (Oxford) 2007;46:1372–4.
10. Richette P, Doherty M, Pascual E, Barskova V, Becce F, Castaneda-Sanabria J, et al. 2016 updated EULAR evidence based recommendations for the management of gout. Ann Rheum Dis 2017;76:29–42.
11. Kuo CF, Grainge MJ, Mallen C, Zhang W, Doherty M. Rising burden of gout in the UK but continuing suboptimal management: a nationwide population study. Ann Rheum Dis 2015;74:661–7.
12. Briesacher BA, Andrade SE, Fouayzi H, Chan KA. Comparison of drug adherence rates among patients with seven different medical conditions. Pharmacotherapy 2008;28:437–43.
13. Duarte-Garcia A, Zamore R, Wong JB. The evidence basis for the American College of Rheumatology practice guidelines. JAMA Intern Med 2018;178:146–8.
14. McLean RM. The long and winding road to clinical guidelines on the diagnosis and management of gout. Ann Intern Med 2017;166: 73–4.
15. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336:924–6.
16. Hultcrantz M, Rind D, Akl EA, Treweek S, Mustafa RA, Iorio A, et al. The GRADE Working Group clarifies the construct of certainty of evidence. J Clin Epidemiol 2017;87:4–13.
17. Alper BS, Oettgen P, Kunnamo I, Iorio A, Ansari MT, Murad MH, et al. Defining certainty of net benefit: a GRADE concept paper. BMJ Open 2019;9:e027445.
18. De Lautour H, Dalbeth N, Taylor WJ. Outcome measures for gout clinical trials: a summary of progress. Curr Treatm Opt Rheumatol 2015;1:156–66.
19. Taylor WJ, Brown M, Aati O, Weatherall M, Dalbeth N. Do patient preferences for core outcome domains for chronic gout studies support the validity of composite response criteria? Arthritis Care Res (Hoboken) 2013;65:1259–64.
20. Schunemann HJ, Mustafa RA, Brozek J, Santesso N, Bossuyt PM, Steingart KR, et al. GRADE guidelines: 22. The GRADE approach for tests and strategies-from test accuracy to patient-important outcomes and recommendations. J Clin Epidemiol 2019;111:69–82.
21. Baraf HS, Becker MA, Gutierrez-Urena SR, Treadwell EL, Vazquez-Mellado J, Rehrig CD, et al. Tophus burden reduction with pegloticase: results from phase 3 randomized trials and open-label extension in patients with chronic gout refractory to conventional therapy. Arthritis Res Ther 2013;15:R137.
22. Strand V, Khanna D, Singh JA, Forsythe A, Edwards NL. Improved health-related quality of life and physical function in patients with refractory chronic gout following treatment with pegloticase: evidence from phase III randomized controlled trials. J Rheumatol 2012;39:1450–7.
23. Sundy JS, Baraf HS, Yood RA, Edwards NL, Gutierrez-Urena SR, Treadwell EL, et al. Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials. JAMA 2011;306:711–20.
24. Tausche AK, Alten R, Dalbeth N, Kopicko J, Fung M, Adler S, et al. Lesinurad monotherapy in gout patients intolerant to a xanthine oxidase inhibitor: a 6-month phase 3 clinical trial and extension study. Rheumatology (Oxford) 2017;56:2170–8.
25. Dalbeth N, Jones G, Terkeltaub R, Khanna D, Kopicko J, Bhakta N, et al. Lesinurad, a selective uric acid reabsorption inhibitor, in combination with febuxostat in patients with tophaceous gout: findings of a phase III clinical trial. Arthritis Rheumatol 2017;69:1903–13.
26. Shoji A, Yamanaka H, Kamatani N. A retrospective study of the relationship between serum urate level and recurrent attacks of gouty arthritis: evidence for reduction of recurrent gouty arthritis with antihyperuricemic therapy. Arthritis Rheum 2004;51:321–5.
27. Dalbeth N, Saag KG, Palmer WE, Choi HK, Hunt B, MacDonald PA, et al. Effects of febuxostat in early gout: a randomized, double-blind, placebo-controlled study. Arthritis Rheumatol 2017;69:2386–95.
28. Levy GD, Rashid N, Niu F, Cheetham TC. Effect of urate-lowering therapies on renal disease progression in patients with hyperuricemia. J Rheumatol 2014;41:955–62.
29. Lu CC, Wu SK, Chen HY, Chung WS, Lee MC, Yeh CJ. Clinical characteristics of and relationship between metabolic components and renal function among patients with early-onset juvenile tophaceous gout. J Rheumatol 2014;41:1878–83.
30. Dalbeth N, House ME, Horne A, Taylor WJ. Reduced creatinine clearance is associated with early development of subcutaneous tophi in people with gout. BMC Musculoskelet Disord 2013;14:363.
Patient global assessment (PGA)
A significant input for the ACR2020 project is the use of Patient global assessment (PGA) as part of the evidence grading. So the best explanation I’ve found so far is for rheumatoid arthritis (RA). Therefore, if necessary, I will include:
Nikiphorou, Elena, Helga Radner, Katerina Chatzidionysiou, Carole Desthieux, Codruta Zabalan, Yvonne van Eijk-Hustings, William G. Dixon, Kimme L. Hyrich, Johan Askling, and Laure Gossec. “Patient global assessment in measuring disease activity in rheumatoid arthritis: a review of the literature.” Arthritis research & therapy 18, no. 1 (2016): 251.
Japanese Gout Guidelines
Hisatome, Ichiro, Kimiyoshi Ichida, Ikuo Mineo, Akira Ohtahara, Kazuhide Ogino, Masanari Kuwabara, Nobukazu Ishizaka et al. “Japanese Society of Gout and Uric & Nucleic Acids 2019 Guidelines for Management of Hyperuricemia and Gout 3rd edition.” Gout and Uric & Nucleic Acids 44, no. Supplement (2020): sp-1.
Beet/Beetroot (Beta Vulgaris)
Mentioned on Facebook which prompted a look at old forums so definitely of interest:

  • El Gamal, Ali A et al. “Beetroot (Beta vulgaris L.) extract ameliorates gentamicin-induced nephrotoxicity associated oxidative stress, inflammation, and apoptosis in rodent model.” Mediators of inflammation vol. 2014 (2014): 983952. doi:10.1155/2014/983952
    I have completed my review of this study. But not yet incorporated it into the Gout Food pages pending a format review.
  • Also chard is same species. But though related, the evidence isn’t strong enough to warrant a separate article or a full study. Because it shows no effect on uric acid in normal rats. But when they are poisoned to artificially raise uric acid, chard will limit some of that increase. (There are no useful quotes.)
    Ozsoy-Sacan, Ozlem et al. “Effects of chard (Beta vulgaris L. var cicla) on the liver of the diabetic rats: a morphological and biochemical study.” Bioscience, biotechnology, and biochemistry vol. 68,8 (2004): 1640-8. doi:10.1271/bbb.68.1640
  • Two related studies consider anti-inflammatory effects of beetroot extracts. Specifically betanin and betalains. One shows reduced inflammation in injured rats.
    Motawi, Tarek K., Samia A. Ahmed, Noha A. El-Boghdady, Nadia S. Metwally, and Noha N. Nasr. “Impact of betanin against paracetamol and diclofenac induced hepato-renal damage in rats.” Biomarkers 25, no. 1 (2020): 86-93.

    The other reviews many health benefits from test-tube, animal, and arthritis patients:

    it is obvious that red beetroot can protect against metabolic syndrome, neurodegenerative diseases, cancer and inflammatory conditions in animal models and possibly in humans.

    Hadipour, Elham, Akram Taleghani, Nilufar Tayarani‐Najaran, and Zahra Tayarani‐Najaran. “Biological effects of red beetroot and betalains: A review.” Phytotherapy Research (2020).

    All these studies indicate that beets and beetroot are potentially excellent for gout sufferers. But without specific studies on gout patients it is impossible to quantify the benefits. Also impossible to say how they might be used in a treatment plan.

Normal Uric Acid
I continue to review the growing number of studies that support the notion that normal uric acid is meaningless and misleading. Because these support my gout campaign: NUANT: Normal Uric Acid? No Thanks! Some studies to review include:

  • Casiglia, Edoardo, Valérie Tikhonoff, Agostino Virdis, Stefano Masi, Carlo M. Barbagallo, Michele Bombelli, Bernardino Bruno et al. “Serum uric acid and fatal myocardial infarction: detection of prognostic cut-off values: The URRAH (Uric Acid Right for Heart Health) study.” Journal of hypertension 38, no. 3 (2020): 412.
  • Desideri, G., G. Castaldo, A. Lombardi, M. Mussap, A. Testa, R. Pontremoli, L. Punzi, and C. Borghi. “Is it time to revise the normal range of serum uric acid levels.” Eur Rev Med Pharmacol Sci 18, no. 9 (2014): 1295-306.
  • Helmersson-Karlqvist, Johanna, Peter Ridefelt, Lars Lind, and Anders Larsson. “Reference values for 34 frequently used laboratory tests in 80-year-old men and women.” Maturitas 92 (2016): 97-101.
  • Yang, Yuanqing, Hongmin Jiang, Aiguo Tang, and Zhongyuan Xiang. “Reference intervals for serum bilirubin, urea, and uric acid in healthy Chinese geriatric population.” Journal of clinical laboratory analysis 32, no. 3 (2018): e22318.
  • Shani, Michal, Shlomo Vinker, Dganit Dinour, Merav Leiba, Gilad Twig, Eliezer J. Holtzman, and Adi Leiba. “High normal uric acid levels are associated with an increased risk of diabetes in lean, normoglycemic healthy women.” The Journal of Clinical Endocrinology & Metabolism 101, no. 10 (2016): 3772-3778.
    Cited in True Normal Uric Acid Range
  • Borghi, Claudio, Enrico Agabiti Rosei, Thomas Bardin, Jesse Dawson, Anna Dominiczak, Jan T. Kielstein, Athanasios J. Manolis, Fernando Perez-Ruiz, and Giuseppe Mancia. “Serum uric acid and the risk of cardiovascular and renal disease.” Journal of hypertension 33, no. 9 (2015): 1729-1741.
  • Feig, Daniel I., Duk-Hee Kang, and Richard J. Johnson. “Uric acid and cardiovascular risk.” New England Journal of Medicine 359, no. 17 (2008): 1811-1821.
  • Niskanen, Leo K., David E. Laaksonen, Kristiina Nyyssönen, Georg Alfthan, Hanna-Maaria Lakka, Timo A. Lakka, and Jukka T. Salonen. “Uric acid level as a risk factor for cardiovascular and all-cause mortality in middle-aged men: a prospective cohort study.” Archives of internal medicine 164, no. 14 (2004): 1546-1551.
  • Verdecchia, Paolo, Giuseppe Schillaci, GianPaolo Reboldi, Fausto Santeusanio, Carlo Porcellati, and Paolo Brunetti. “Relation between serum uric acid and risk of cardiovascular disease in essential hypertension: the PIUMA study.” Hypertension 36, no. 6 (2000): 1072-1078.
  • Another problem with Normal Uric Acid is joint temperature. It is bad enough that the cut-off for healthy people is mismanaged by laboratories when they calculate the range. Because hyperuricemia is a recognized illness that should exclude some results (need to find the “illness code” for hyperuricemia). This is made much worse by the fact that hyperuricemia definition should recognise joint temperatures. So the two relevant studies are:
    • Loeb, John N. “The influence of temperature on the solubility of monosodium urate.” Arthritis & Rheumatism: Official Journal of the American College of Rheumatology 15, no. 2 (1972): 189-192.
    • Oosterveld, F. G. J., Johannes J. Rasker, J. W. G. Jacobs, and H. J. A. Overmars. “The effect of local heat and cold therapy on the intraarticular and skin surface temperature of the knee.” Arthritis & Rheumatism: Official Journal of the American College of Rheumatology 35, no. 2 (1992): 146-151.

GoutPal Research Articles

These are sources of information that relate to existing articles. So when I get time, I will publish a review here. Then I will update the related article.

Is Allopurinol Taken For Life?
3 out of 5 references to publish:

  • Li-Yu, J., E. O. Salido, S. Manahan, J. J. Lichauco, J. P. Lorenzo, K. T. Torralba, A. A. Raso, L. C. Roberto, P. Santos Estrella, and L. M. Maceda. “Philippine Clinical Practice Guidelines for the Management of Gout Technical Review Committee Members.”
  • Stamp, Lisa K. “Major unanswered questions in the clinical gout field.” Current opinion in rheumatology 29, no. 2 (2017): 171-177.
  • Perez-Ruiz, Fernando, Ana Maria Herrero-Beites, and Loreto Carmona. “A two-stage approach to the treatment of hyperuricemia in gout: The “dirty dish” hypothesis.” Arthritis & Rheumatism 63, no. 12 (2011): 4002-4006.
Low Purine Diet
3 out of 4 references to publish:

  • Lockyer, S., and S. Stanner. “Diet and gout–what is the role of purines?.” Nutrition Bulletin 41, no. 2 (2016): 155-166.
  • Al-Masri, Soheir Ahmed. “BENEFICIAL ROLE OF HIGH PLANT PROTEINS IN THE TREATMENT AGAINST HYPERURICEMIA IN EXPERIMENTAL RATS.” JAPS, Journal of Animal and Plant Sciences 26, no. 3 (2016): 619-626.
  • Chiu, Tina HT, Chin-Hsiu Liu, Chia-Chen Chang, Ming-Nan Lin, and Chin-Lon Lin. “Vegetarian diet and risk of gout in two separate prospective cohort studies.” Clinical Nutrition 39, no. 3 (2020): 837-844.
    Note: this study also needs to update Why Vegan Diet is Worst for Gout. Also, it is probably significant enough to add as a fourth Gout Foundation Diet choice. Though that depends on the strength of evidence revealed by this study and those that cite it.
Stress and Gout
Following readers comments, I will review studies of gout related to anxiety and depression. So far, I’ve spotted three a few to start with. But there may be others…

  1. Fu, Ting, Haixia Cao, Rulan Yin, Lijuan Zhang, Qiuxiang Zhang, Liren Li, and Zhifeng Gu. “Associated factors with functional disability and health-related quality of life in Chinese patients with gout: a case-control study.” BMC Musculoskeletal Disorders 18, no. 1 (2017): 429.
  2. Kawada, Tomoyuki. “Gout and erectile dysfunction with special reference to depression.” European Journal of Internal Medicine 31 (2016): e13.
  3. WAN, Ling-ling, Xue-fang LIU, and Fang ChEN. “Effect of mental nursing interventions on the anxiety-depressing emotion and the life quality of patients who with gout arthritis [J].” Jilin Medical Journal 25 (2013).
  4. Hsu, Chao-Yu, Cheng-Li Lin, and Chia-Hung Kao. “Gout is associated with organic and psychogenic erectile dysfunction.” European journal of internal medicine 26, no. 9 (2015): 691-695.
  5. Fu, Ting, Haixia Cao, Rulan Yin, Lijuan Zhang, Qiuxiang Zhang, Liren Li, Xingmei Feng, and Zhifeng Gu. “Depression and anxiety correlate with disease-related characteristics and quality of life in Chinese patients with gout: a case-control study.” Psychology, health & medicine 23, no. 4 (2018): 400-410.
  6. Mak, Anselm, Catherine So-Kum Tang, Moon-Fai Chan, Alicia Ai-Cia Cheak, and Roger Chun-Man Ho. “Damage accrual, cumulative glucocorticoid dose and depression predict anxiety in patients with systemic lupus erythematosus.” Clinical rheumatology 30, no. 6 (2011): 795-803.
  7. Prior, James Andrew, Christian D. Mallen, Priyanka Chandratre, Sara Muller, Jane Richardson, and Edward Roddy. “Gout characteristics associate with depression, but not anxiety, in primary care: baseline findings from a prospective cohort study.” Joint Bone Spine 83, no. 5 (2016): 553-558.
  8. Prior, J. A., R. Ogollah, S. Muller, P. Chandratre, E. Roddy, and C. D. Mallen. “Gout, anxiety, and depression in primary care: a matched retrospective cohort study.” Scandinavian journal of rheumatology 44, no. 3 (2015): 257-258.

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