Skip to main content

Advertisement

SpringerLink
Log in

Serum uric acid as a sensitive concordant marker with lupus nephritis and new onset of renal damage: a prospective cohort study

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Objective

The objectives of this study are to assess serum different uric acid levels among systemic lupus erythematosus patients with or without active lupus nephritis in comparison to healthy controls and to study the relation of baseline uric acid levels to the development of new-onset renal damage in lupus nephritis.

Methods

This is a case-control study followed by a prospective cohort of systemic lupus erythematosus (SLE) patients. Three groups were included; all were having normal kidney function, 25 SLE patients with recently diagnosed active lupus nephritis (LN), 26 SLE patients without LN, and 38 healthy controls. Serum uric acid (SUA)and serum creatinine were done for all groups; for SLE patients, 24-h protein in the urine, urinalysis, C3, C4 levels, anti-DNA, anti-ENA antibodies, SLE Disease Activity Index (SLEDAI), and SLICC/ACR damage index (SDI) evaluation were also calculated. Follow-up was done with clinical and laboratory assessment including SUA, with SLEDAI and SDI evaluation.

Results

Serum uric acid was significantly higher in SLE patients with active LN than the other two groups (p < 0.05), a cutoff value of serum uric acid associated with lupus nephritis onset was 0.41 mmol/L with a sensitivity of 58% and specificity of 100%, however, C3 and C4 showed very low sensitivity and specificity. During follow-up, all patients with LN with baseline serum uric acid ≥ 0.52 mmol/L were associated with new-onset renal damage within 43 months.

Conclusions

High-serum uric acid levels showed a significant association with lupus nephritis onset and new onset of renal damage.

Key Points

• Serum uric acid is a cheap, rapid, and popular test available in most of the worldwide laboratories; its higher levels showed a significant association with lupus nephritis onset and new onset of renal damage

• The current work is the largest study done on lupus nephritis with strict control to the confound risk factors that are associated with the increase of the uric acid levels; moreover, it is the first study to assess such relation in Saudi population

• Uric acid could have a role in the pathogenesis of lupus nephritis patients and consequent renal damage

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

Data available on reasonable request.

References

  1. Von Feldt JM (1995) Systemic lupus erythematosus: recognizing its various presentations. Postgrad Med 97(4):79–94

    Article  Google Scholar 

  2. Danila MI, Pons-Estel GJ, Zhang J, Vila LM, Reveille JD, Alarcon GS (2009) Renal damage is the most important predictor of mortality within the damage index: data from LUMINA LXIV, a multiethnic US cohort. Rheumatology. 48(5):542–545

    Article  Google Scholar 

  3. Chi S, Yu Y, Shi J, Zhang Y, Yang J, Yang L, Liu X (2015) Antibodies against C1q are a valuable serological marker for identification of systemic lupus erythematosus patients with active lupus nephritis. Dis Markers. 2015:450351. https://doi.org/10.1155/2015/450351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Bardin T, Richette P (2014) Definition of hyperuricemia and gouty conditions. Curr Opin Rheumatol 26(2):186–191

    Article  CAS  Google Scholar 

  5. Chen LY, Zhu WH, Chen ZW, Dai HL, Ren JJ, Chen JH, Chen LQ, Fang LZ (2007) Relationship between hyperuricemia and metabolic syndrome. J Zhejiang Univ Sci B 8(8):593–598

    Article  CAS  Google Scholar 

  6. Kim SY, Guevara JP, Kim KM, Choi HK, Heitjan DF, Albert DA (2010) Hyperuricemia and coronary heart disease: a systematic review and meta-analysis. Arthritis Care Res 62(2):170–180

    Google Scholar 

  7. Li M, Hou W, Zhang X, Hu L, Tang Z (2014) Hyperuricemia and risk of stroke: a systematic review and meta-analysis of prospective studies. Atherosclerosis. 232(2):265–270

    Article  CAS  Google Scholar 

  8. Li L, Yang C, Zhao Y, Zeng X, Liu F, Fu P (2014) Is hyperuricemia an independent risk factor for new-onset chronic kidney disease: a systematic review and meta-analysis based on observational cohort studies. BMC Nephrol 15(1):122

    Article  Google Scholar 

  9. Sheikh M, Movassaghi S, Khaledi M, Moghaddassi M (2015) Hyperuricemia in systemic lupus erythematosus: is it associated with the neuropsychiatric manifestations of the disease? Rev Bras Reumatol (Engl Ed) 56(6):471–477

    Article  Google Scholar 

  10. Kim KJ, Baek IW, Park YJ, Yoon CH, Kim WU, Cho CS (2015) High levels of uric acid in systemic lupus erythematosus is associated with pulmonary hypertension. Int J Rheum Dis 18(5):524–532

    Article  CAS  Google Scholar 

  11. Kang D, Kanellis J (2005) Uric acid as a mediator of endothelial dysfunction, inflammation and vascular disease. Semin Nephrol 25(1):39–42

    Article  Google Scholar 

  12. Yang Z, Liang Y, Xi W, Zhu Y, Li C, Zhong R (2011) Association of serum uric acid with lupus nephritis in systemic lupus erythematosus. Rheumatol Int 31(6):743–748

    Article  CAS  Google Scholar 

  13. Calich AL, Borba E, Ugolini-Lopes M, da Rocha L, Bonfá E, Fuller R (2018) Serum uric acid levels are associated with lupus nephritis in patients with normal renal function. Clin Rheumatol 37(5):1223–1228

    Article  Google Scholar 

  14. Reátegui-Sokolova C, Ugarte-Gil MF, Gamboa-Cárdenas RV, Zevallos F, Cucho-Venegas JM, Alfaro-Lozano JL, Medina M, Rodriguez-Bellido Z, Pastor-Asurza CA, Alarcón GS, Perich-Campos RA (2017) Serum uric acid levels contribute to new renal damage in systemic lupus erythematosus patients. Clin Rheumatol 36(4):845–852

    Article  Google Scholar 

  15. Hochberg M (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40(9):1725–1725

    Article  CAS  Google Scholar 

  16. Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD et al (2012) American College of Rheumatology Guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res 64(6):797–808

    Article  Google Scholar 

  17. Gladman DD, Ibanez D, Urowitz MB (2002) Systemic lupus erythematosus disease activity index 2000. J Rheumatol 29(2):288–291

    PubMed  Google Scholar 

  18. Gladman D, Ginzler E, Goldsmith C, Fortin P, Liang M, Urowitz M et al (1996) The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum 39(3):363–369

    Article  CAS  Google Scholar 

  19. Gromadziński L, Januszko-Giergielewicz B, Pruszczyk P (2015) Hyperuricemia is an independent predictive factor for left ventricular diastolic dysfunction in patients with chronic kidney disease. Adv Clin Exp Med 24(1):47–54

    Article  Google Scholar 

  20. Kushiyama A, Nakatsu Y, Matsunaga Y, Yamamotoya T, Mori K, Ueda K, Inoue Y et al (2016) Role of uric acid metabolism-related inflammation in the pathogenesis of metabolic syndrome components such as atherosclerosis and nonalcoholic steatohepatitis. Mediators Inflamm 2016:8603164

    Article  Google Scholar 

  21. Mazzali M, Hughes J, Kim Y, Jeffnerson J, Kang D, Gordon K, Lan H, Kivlighn S, Johnson R (2001) Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension. 38(5):1101–1106

    Article  CAS  Google Scholar 

  22. Ohara Y, Peterson TE, Harrison DG (1993) Hypercholesterolemia increases endothelial superoxide anion production. J Clin Investig 91(6):2546–2551. https://doi.org/10.1172/JCI116491

    Article  CAS  PubMed  Google Scholar 

  23. Ejaz A, Mu W, Kang D, Roncal C, Sautin Y, Henderson G, Tabah-Fisch I, Keller B, Beaver T, Nakagawa T, Johnson R (2007) Could uric acid have a role in acute renal failure?.Clinical. J Am Soc Nephrol 2(1):16–21

    Article  CAS  Google Scholar 

  24. Ruggiero C, Cherubini A, Ble A, Bos A, Maggio M, Dixit V, Lauretani F, Bandinelli S, Senin U, Ferrucci L (2006) Uric acid and inflammatory markers. Eur Heart J 27(10):1174–1181

    Article  CAS  Google Scholar 

  25. Giclas P, Ginsberg M, Cooper N (1979) Immunoglobulin G independent activation of the classical complement pathway by monosodium urate crystals. J Clin Investig 63(4):759–764

    Article  CAS  Google Scholar 

  26. Martinon F, Pétrilli V, Mayor A, Tardivel A, Tschopp J (2006) Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 440(7081):237–241. https://doi.org/10.1038/nature04516

    Article  CAS  PubMed  Google Scholar 

  27. Fu R, Guo C, Wang S, Huang Y, Jin O, Hu H, Chen J, Xu B, Zhou M, Zhao J, Sung SSJ, Wang H, Gaskin F, Yang N, Fu SM (2017) Podocyte activation of NLRP3 inflammasomes contributes to the development of proteinuria in lupus nephritis. Arthritis Rheum 69:1636–1646. https://doi.org/10.1002/art.40155

    Article  CAS  Google Scholar 

  28. Ka SM, Lin JC, Lin TJ, Liu FC, Chao LK, Ho CL, Yeh LT, Sytwu HK, Hua KF, Chen A (2015) Citral alleviates an accelerated and severe lupus nephritis model by inhibiting the activation signal of NLRP3 inflammasome and enhancing Nrf2 activation. Arthritis Res Ther 17:331. https://doi.org/10.1186/s13075-015-0844-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Goicoechea M, de Vinuesa S, 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(8):1388–1393

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the support provided by the officials of the studied hospital for facilitating the administrative aspects of the research. Special thanks to the participant patients for their cooperation.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department of Rheumatology, Rehabilitation and Physical Medicine, Benha University, Benha, Egypt

    Basant Elnady

  2. Department of Rheumatology, Al Hada Armed Forces Hospital, Al Hada, Saudi Arabia

    Basant Elnady & Mohammed Attar

  3. Department of Internal Medicine, King Faisal Medical Complex, Taif, Saudi Arabia

    Abdulaziz Almalki

  4. Research administration, Al-Hada Armed Forces Hospital, Al Hada, Saudi Arabia

    Moataz M. Abdel-Fattah

  5. Department of Public Health and Community Medicine, Menoufia University, Sheben Al Koom, Egypt

    Dalia El-Sayed Desouky

Authors
  1. Basant Elnady
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abdulaziz Almalki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Moataz M. Abdel-Fattah
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dalia El-Sayed Desouky
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohammed Attar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Basant Elnady.

Ethics declarations

Conflict of interest

The authors declare that there is no conflict of interest.

Ethics approval

This study complies with the Declaration of Helsinki and was approved by the local ethical research committee. All patients provided a written informed consent.

Consent to participate

All authors declare their participation.

Consent for publication

All authors agree for publication.

Code availability

Not applicable.

Additional information

Publisher’s note

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

Electronic supplementary material

ESM 1

Receiver-operating characteristic (ROC) curve of uric acid and new renal damage (JPG 34 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Elnady, B., Almalki, A., Abdel-Fattah, M.M. et al. Serum uric acid as a sensitive concordant marker with lupus nephritis and new onset of renal damage: a prospective cohort study. Clin Rheumatol 40, 1827–1834 (2021). https://doi.org/10.1007/s10067-020-05473-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-020-05473-x

Keywords

Search

Navigation