Horm Metab Res 2024; 56(06): 455-462
DOI: 10.1055/a-2294-6749
Original Article: Endocrine Care

Serum Uric Acid Combined with Homocysteine as a Predictive Biomarker of Lupus Nephritis

Juan Zhang
1   Department of Rheumatology, Lanzhou University Second Hospital, Lanzhou, Gansu, China
Jingjing Tian
1   Department of Rheumatology, Lanzhou University Second Hospital, Lanzhou, Gansu, China
Xiaoyuan Wang
1   Department of Rheumatology, Lanzhou University Second Hospital, Lanzhou, Gansu, China
Haili Shen
1   Department of Rheumatology, Lanzhou University Second Hospital, Lanzhou, Gansu, China
› Author Affiliations
Funding Information Innovation Base and Talent Plan of Gansu Province — Grant number 21JR7RA437 Science and Technology Project of Gansu Province — Grant number 21JR1RA134 Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital (CY2021-MS-A18).


Serum uric acid (UA) and homocysteine (Hcy) are potential biomarkers of systemic lupus erythematosus (SLE). In this study, the expressions of UA and Hcy in SLE patients and the predictive value of these two parameters for lupus nephritis (LN) were studied. A total of 476 SLE patients were recruited to this case-control study, of which 176 SLE patients diagnosed with LN and 300 without LN. Serum UA and Hcy levels were analyzed. Multivariate logistic regression analysis was used to evaluate the relationship between serum UA and Hcy and LN. The receiver operating characteristic (ROC) curves were used to predict the role of combination of serum UA and Hcy in LN. We found that serum UA and Hcy levels in SLE patients with LN were significantly higher than those in controls (p<0.05). Multivariate logistic regressions showed that serum UA (OR+=+1.003, 95+% CI: 1.001–1.006, p+=+0.003), apolipoprotein B (Apo B) (OR+=+21.361, 95+% CI: 2.312–195.373, p+=+0.007) and Hcy (OR+=+1.042, 95+% CI: 1.011–1.080, p+=+0.014) were independent markers of LN. Combined serum UA and Hcy revealed a better result (AUC+=+0.718, 95+% CI: 0.670–0.676, p<0.001) in prediction of LN compared to that of the serum UA (AUC+=+0.710) and Hcy (AUC+=+0.657) independently. In conclusion, serum UA and Hcy could be predictive biomarkers of LN, and joint detection of serum UA and Hcy might be useful in the clinical setting.

Publication History

Received: 26 May 2023

Accepted after revision: 11 March 2024

Article published online:
06 May 2024

© 2024. Thieme. All rights reserved.

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  • References

  • 1 Almaani S, Meara A, Rovin BH. Update on lupus nephritis. Clin J Am Soc Nephrol 2016; 12: 825-835
  • 2 Morell M, Pérez-Cózar F, Marañón C. Immune-related urine biomarkers for the diagnosis of lupus nephritis. Int J Mol Sci 2020; 22: 7143
  • 3 Lech M, Anders HJ. The pathogenesis of lupus nephritis. J Am Soc Nephrol 2013; 24: 1357-1366
  • 4 Anders HJ, Saxena R, Zhao MH. et al. Lupus nephritis. Nat Rev Dis Primers 2020; 6: 7
  • 5 Yavuz S, Lipsky PE. Current status of the evaluation and management of lupus patients and future prospects. Front Med 2021; 8: 682544
  • 6 Dos Santos M, Veronese FV, Moresco RN. Uric acid and kidney damage in systemic lupus erythematosus. Clin Chim Acta 2020; 508: 197-205
  • 7 Ugolini-Lopes MR, Gavinier SS, Leon E. et al. Is serum uric acid a predictor of long-term renal outcome in lupus nephritis?. Clin Rheumatol 2019; 38: 2777-2783
  • 8 Calich AL, Borba EF, Ugolini-Lopes MR. et al. Serum uric acid levels are associated with lupus nephritis in patients with normal renal function. Clin Rheumatol 2018; 37: 1223-1228
  • 9 Moroni G, Novembrino C, Quaglini S. et al. Oxidative stress and homocysteine metabolism in patients with lupus nephritis. Lupus 2010; 19: 65-72
  • 10 Sam NB, Zhang Q, Li BZ. et al. Serum/plasma homocysteine levels in patients with systemic lupus erythematosus: a systematic review and meta-analysis. Clin Rheumatol 2020; 39: 1725-1736
  • 11 Tsai TY, Lee TH, Wang HH. et al. Serum homocysteine, folate, and vitamin B levels in patients with systemic lupus erythematosus: a meta-analysis and meta-regression. J Am Coll Nutr 2020; 40: 443-453
  • 12 Aringer M, Johnson SR. Classifying and diagnosing systemic lupus erythematosus in the 21st century. Rheumatology 2020; 59: v4-v11
  • 13 Jaryal A, Vikrant S. Current status of lupus nephritis. Indian J Med Res 2017; 145: 167-178
  • 14 La Paglia GMC, Leone MC, Lepri G. et al. One year in review 2017: systemic lupus erythematosus. Clin Exp Rheumatol 2017; 35: 551-561
  • 15 Kwon OC, Lee JS, Ghang B. et al. Predicting eventual development of lupus nephritis at the time of diagnosis of systemic lupus erythematosus. Semin Arthritis Rheum 2018; 48: 462-466
  • 16 Kronbichler A, Brezina B, Gauckler P. et al. Refractory lupus nephritis: when, why and how to treat. Autoimmun Rev 2019; 18: 510-518
  • 17 Zampeli E, Klinman DM, Gershwin ME. et al. A comprehensive evaluation for the treatment of lupus nephritis. J Autoimmun 2017; 78: 1-10
  • 18 Parodis I, Tamirou F, Houssiau FA. Prediction of prognosis and renal outcome in lupus nephritis. Lupus Sci Med 2020; 7: e000389
  • 19 Umeda R, Ogata S, Hara S. et al. Comparison of the 2018 and 2003 International Society of Nephrology/Renal Pathology Society classification in terms of renal prognosis in patients of lupus nephritis: a retrospective cohort study. Arthritis Res Ther 2020; 22: 260
  • 20 Yap DY, Yung S, Chan TM. Lupus nephritis: An update on treatments and pathogenesis. Nephrology (Carlton) 2018; 23: 80-83
  • 21 Ames BN, Cathcart R, Schwiers E. et al. Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci U S A 1981; 78: 6858-6862
  • 22 Ejaz AA, Mu W, Kang D-H. et al. Could uric acid have a role in acute renal failure?. Clin J Am Soc Nephrol 2007; 2: 16-21
  • 23 Roncal CA, Mu W, Croker B. et al. Effect of elevated serum uric acid on cisplatin-induced acute renal failure. Am J Physiol Renal Physiol 2007; 292: F116-F122
  • 24 Oh TR, Choi HS, Kim CS. et al. Serum uric acid is associated with renal prognosis of lupus nephritis in women but not in Men. J Clin Med 2020; 9: 773
  • 25 Giclas PC, Ginsberg MH, Cooper NR. Immunoglobulin G independent activation of the classical complement pathway by monosodium urate crystals. J Clin Med 1979; 63: 759-764
  • 26 Yang Z, Liang Y, Xi W. et al. Association of serum uric acid with lupus nephritis in systemic lupus erythematosus. Rheumatol Int 2011; 31: 743-748
  • 27 Zaric BL, Obradovic M, Bajic V. et al. Homocysteine and hyperhomocysteinaemia. Curr Med Chem 2019; 26: 2948-2961
  • 28 Berglund S, Södergren A, Wållberg Jonsson S. et al. Atherothrombotic events in rheumatoid arthritis are predicted by homocysteine – a six-year follow-up study. Clin Exp Rheumatol 2009; 27: 822-825
  • 29 Bonciani D, Antiga E, Bonciolini V. et al. Homocysteine serum levels are increased and correlate with disease severity in patients with lupus erythematosus. Clin Exp Rheumatol 2016; 34: 76-81
  • 30 Timlin H, Manno R, Douglas H. Hyperhomocysteinemia and lupus nephritis. Cureus 2019; 11: e5065
  • 31 Karmin O, Siow YL. Metabolic imbalance of homocysteine and hydrogen sulfide in Kidney Disease. Curr Med Chem 2018; 25: 367-377