Skip to main content

Advertisement

SpringerLink
Log in

Uric acid and risk of diabetic kidney disease

  • Review
  • Published:
Journal of Nephrology Aims and scope Submit manuscript

Abstract

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD) in the Western world. Better control of glycemia and blood pressure, including renin-angiotensin system blockade (RASB), appear to have slowed DKD progression rate but have been unable to substantially decrease the annual incidence of new cases of DKD related ESKD. Thus, new treatment targets are needed. Higher levels of serum uric acid (SUA) have been associated with increased risk and progression of DKD in persons with types 1 (T1D) and 2 (T2D) diabetes and of chronic kidney disease (CKD) in general. This review presents the epidemiological, clinical, and clinical trial evidence regarding the hypothesis that SUA reduction could slow progression of DKD and/or CKD in general.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. de Boer IH, Sun W, Cleary PA, Lachin JM, Molitch ME, Steffes MW, Zinman B (2011) Intensive diabetes therapy and glomerular filtration rate in type 1 diabetes. N Engl J Med 365:2366–2376. https://doi.org/10.1056/NEJMoa1111732

    Article  CAS  PubMed  Google Scholar 

  2. Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde R, Raz I (2001) Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 345:851–860. https://doi.org/10.1056/NEJMoa011303

    Article  CAS  PubMed  Google Scholar 

  3. Afkarian M, Zelnick LR, Hall YN, Heagerty PJ, Tuttle K, Weiss NS, de Boer IH (2016) Clinical manifestations of kidney disease among US adults with diabetes, 1988-2014. JAMA 316:602–610. https://doi.org/10.1001/jama.2016.10924

    Article  PubMed Central  PubMed  Google Scholar 

  4. Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, Malanda B (2018) IDF diabetes Atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract 138:271–281. https://doi.org/10.1016/j.diabres.2018.02.023

    Article  CAS  PubMed  Google Scholar 

  5. Hovind P, Rossing P, Tarnow L, Johnson RJ, Parving HH (2009) Serum uric acid as a predictor for development of diabetic nephropathy in type 1 diabetes: an inception cohort study. Diabetes 58:1668–1671

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Jalal DI, Rivard CJ, Johnson RJ, Maahs DM, McFann K, Rewers M, Snell-Bergeon JK (2010) 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 Transpl 25:1865–1869

    Article  CAS  Google Scholar 

  7. Pacilli A, Viazzi F, Fioretto P, Giorda C, Ceriello A, Genovese S, Russo G, Guida P, Pontremoli R, De Cosmo S (2017) Group AM-AS: epidemiology of diabetic kidney disease in adult patients with type 1 diabetes in Italy: the AMD-Annals initiative. Diabetes Metab Res Rev. https://doi.org/10.1002/dmrr.2873

    Article  PubMed  Google Scholar 

  8. Zoppini G, Targher G, Chonchol M, Ortalda V, Abaterusso C, Pichiri I, Negri C, Bonora E (2012) Serum uric acid levels and incident chronic kidney disease in patients with type 2 diabetes and preserved kidney function. Diabetes Care 35:99–104. https://doi.org/10.2337/dc11-1346

    Article  CAS  PubMed  Google Scholar 

  9. Ficociello LH, Rosolowsky ET, Niewczas MA, Maselli NJ, Weinberg JM, Aschengrau A, Eckfeldt JH, Stanton RC, Galecki AT, Doria A, Warram JH, Krolewski AS (2010) High-normal serum uric acid increases risk of early progressive renal function loss in type 1 diabetes: results of a 6-year follow-up. Diabetes Care 33:1337–1343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hayashino Y, Okamura S, Tsujii S, Ishii H (2016) Association of serum uric acid levels with the risk of development or progression of albuminuria among Japanese patients with type 2 diabetes: a prospective cohort study [Diabetes Distress and Care Registry at Tenri (DDCRT 10)]. Acta Diabetol 53:599–607. https://doi.org/10.1007/s00592-015-0825-x

    Article  CAS  PubMed  Google Scholar 

  11. Chang YH, Lei CC, Lin KC, Chang DM, Hsieh CH, Lee YJ (2016) 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 32:557–564. https://doi.org/10.1002/dmrr.2768

    Article  CAS  PubMed  Google Scholar 

  12. Johnson RJ, Segal MS, Srinivas T, Ejaz A, Mu W, Roncal C, Sanchez-Lozada LG, Gersch M, Rodriguez-Iturbe B, Kang DH, Acosta JH (2005) Essential hypertension, progressive renal disease, and uric acid: a pathogenetic link? J Am Soc Nephrol 16:1909–1919

    Article  CAS  PubMed  Google Scholar 

  13. Mazzali M, Hughes J, Kim YG, Jefferson JA, Kang DH, Gordon KL, Lan HY, Kivlighn S, Johnson RJ (2001) Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension 38:1101–1106

    Article  CAS  PubMed  Google Scholar 

  14. Mazzali M, Kanellis J, Han L, Feng L, Xia YY, Chen Q, Kang DH, Gordon KL, Watanabe S, Nakagawa T, Lan HY, Johnson RJ (2002) Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism. Am J Physiol Renal Physiol 282:F991–F997

    Article  CAS  PubMed  Google Scholar 

  15. Siu YP, Leung KT, Tong MK, Kwan TH (2006) Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. Am J Kidney Dis 47:51–59

    Article  CAS  PubMed  Google Scholar 

  16. Goicoechea M, de Vinuesa SG, Verdalles U, Ruiz-Caro C, Ampuero J, Rincon A, Arroyo D, Luno J (2010) Effect of allopurinol in chronic kidney disease progression and cardiovascular risk. Clin J Am Soc Nephrol 5:1388–1393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Miao Y, Ottenbros SA, Laverman GD, Brenner BM, Cooper ME, Parving HH, Grobbee DE, Shahinfar S, de Zeeuw D, Lambers Heerspink HJ (2011) Effect of a reduction in uric acid on renal outcomes during Losartan treatment: a post hoc analysis of the reduction of endpoints in non-insulin-dependent diabetes mellitus with the angiotensin II Antagonist Losartan Trial. Hypertension 58:2–7

    Article  CAS  PubMed  Google Scholar 

  18. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE (2015) Investigators E-RO: empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 373:2117–2128. https://doi.org/10.1056/NEJMoa1504720

    Article  CAS  PubMed  Google Scholar 

  19. Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, Johansen OE, Woerle HJ, Broedl UC, Zinman B (2016) Investigators E-RO: empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 375:323–334. https://doi.org/10.1056/NEJMoa1515920

    Article  CAS  PubMed  Google Scholar 

  20. Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, Edwards R, Agarwal R, Bakris G, Bull S, Cannon CP, Capuano G, Chu PL, de Zeeuw D, Greene T, Levin A, Pollock C, Wheeler DC, Yavin Y, Zhang H, Zinman B, Meininger G, Brenner BM, Mahaffey KW, Investigators CT (2019) Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 380:2295–2306. https://doi.org/10.1056/NEJMoa1811744

    Article  CAS  PubMed  Google Scholar 

  21. Sato Y, Feig DI, Stack AG, Kang DH, Lanaspa MA, Ejaz AA, Sanchez-Lozada LG, Kuwabara M, Borghi C, Johnson RJ (2019) The case for uric acid-lowering treatment in patients with hyperuricaemia and CKD. Nat Rev Nephrol 15:767–775. https://doi.org/10.1038/s41581-019-0174-z

    Article  CAS  PubMed  Google Scholar 

  22. Doria A, Galecki AT, Spino C, Pop-Busui R, Cherney DZ, Lingvay I, Parsa A, Rossing P, Sigal RJ, Afkarian M, Aronson R, Caramori ML, Crandall JP, de Boer IH, Elliott TG, Goldfine AB, Haw JS, Hirsch IB, Karger AB, Maahs DM, McGill JB, Molitch ME, Perkins BA, Polsky S, Pragnell M, Robiner WN, Rosas SE, Senior P, Tuttle KR, Umpierrez GE, Wallia A, Weinstock RS, Wu C, Mauer M (2020) PERL Study Group: serum urate lowering with allopurinol and kidney function in type 1 diabetes. N Engl J Med 382:2493–2503. https://doi.org/10.1056/NEJMoa1916624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Badve S, Pascoe E, Tiku A, Boudville N, Brown FG, Cass A, Clarke P, Dalbeth N, Day RO, de Zoysa J, Douglas B, Faull R, Harris D, Hawley C, Jones GR, Kanellis J, Palmer S, Perkovic V, Rangan G, Reidlinger D, Robison L, Walker RJ, Walters G, Johnson DW (2020) CKD-FIX Study Investigators: effects of allopurinol on the progression of chronic kidney disease. N Engl J Med 382:2504–2513. https://doi.org/10.1056/NEJMoa1915833

    Article  CAS  PubMed  Google Scholar 

  24. Afkarian M, Polsky S, Parsa A, Aronson R, Caramori ML, Cherney DZ, Crandall JP, de Boer IH, Elliott TG, Galecki AT, Goldfine AB, Haw JS, Hirsch IB, Karger AB, Lingvay I, Maahs DM, McGill JB, Molitch ME, Perkins BA, Pop-Busui R, Pragnell M, Rosas SE, Rossing P, Senior P, Sigal RJ, Spino C, Tuttle KR, Umpierrez GE, Wallia A, Weinstock RS, Wu C, Mauer M, Doria A (2019) PERL Study Group: preventing early renal loss in diabetes (PERL) Study: a randomized double-blinded trial of allopurinol—rationale, design, and baseline data. Diabetes Care 42:1454–1463. https://doi.org/10.2337/dc19-0342

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. National Kidney F (2012) KDOQI clinical practice guideline for diabetes and CKD: 2012 update. Am J Kidney Dis 60:850–886. https://doi.org/10.1053/j.ajkd.2012.07.005

    Article  Google Scholar 

  26. Choi HK, Ford ES (2007) Prevalence of the metabolic syndrome in individuals with hyperuricemia. Am J Med 120:442–447. https://doi.org/10.1016/j.amjmed.2006.06.040

    Article  PubMed  Google Scholar 

  27. Ahola AJ, Sandholm N, Forsblom C, Harjutsalo V, Dahlstrom E, Groop PH, FinnDiane Study G (2017) The serum uric acid concentration is not causally linked to diabetic nephropathy in type 1 diabetes. Kidney Int 91:1178–1185. https://doi.org/10.1016/j.kint.2016.11.025

    Article  CAS  PubMed  Google Scholar 

  28. Jordan DM, Choi HK, Verbanck M, Topless R, Won HH, Nadkarni G, Merriman TR, Do R (2019) No causal effects of serum urate levels on the risk of chronic kidney disease: a Mendelian randomization study. PLoS Med 16:e1002725. https://doi.org/10.1371/journal.pmed.1002725

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and Juvenile Diabetes Research Foundation (JDRF) for their support of the Preventing Early Renal Loss in Diabetes (PERL) clinical trial.

Author information

Authors and Affiliations

  1. Department of Pediatrics and Medicine, University of Minnesota School of Medicine, 515 Delaware St SE, Room 13-271 Moos Tower, Minneapolis, MN, 55455, USA

    Michael Mauer

  2. Research Division, Section on Genetics and Epidemiology, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, One Joslin Place, Boston, MA, 02215, USA

    Alessandro Doria

Authors
  1. Michael Mauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alessandro Doria
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Michael Mauer or Alessandro Doria.

Ethics declarations

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical statement

The PERL trial was conducted in accordance with the principles of the Declaration of Helsinki. The protocol was approved by the ethical committees of all institutions participating in the study, and all participants provided written informed consent.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mauer, M., Doria, A. Uric acid and risk of diabetic kidney disease. J Nephrol 33, 995–999 (2020). https://doi.org/10.1007/s40620-020-00796-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40620-020-00796-z

Keywords

Search

Navigation