Skip to main content
Log in

Urinary MCP-1 and TWEAK as non-invasive markers of disease activity and treatment response in patients with lupus nephritis in South Africa

  • Nephrology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Background

Treatment of patients with lupus nephritis (LN) requires judicious use of immunosuppression. Novel biomarkers may be useful for monitoring disease activity and treatment response. We assessed the utility of urinary monocyte chemoattractant protein-1 (uMCP-1) and urinary tumour necrosis factor-like weak inducer of apoptosis (uTWEAK) for disease activity and treatment response monitoring in South Africans with LN.

Methods

We recruited consenting patients with active LN confirmed on kidney biopsy. Urinary levels of MCP-1 and TWEAK were assayed at baseline and after completion of induction therapy using ELISA methods. We also collected relevant demographic, clinical and biochemical data for patients included in this study.

Results

The mean age of patients in this study was 29.8 ± 10.7 years, 60% were patients of mixed ancestry, 70% had proliferative LN and mean spot urine proteinuria at baseline was 0.37 (0.18–0.59) g/mmolCr. At completion of induction therapy, the level of uMCP-1 had reduced to 314.5 (IQR: 197.0–622) pg/mgCr from a baseline of 1092.7 (IQR 578.6–1848) pg/mgCr (P = 0.06) while uTWEAK had reduced to 36.0 (IQR 17.0–88.0) pg/mgCr from 159.0 (IQR: 88.5–295.5) pg/mgCr (P = 0.03). For patients reaching early complete or partial remission (n = 17), both biomarkers had significantly declined in their urine: uMCP-1 (P = 0.018) and uTWEAK (P = 0.015). There was no reduction of both biomarkers in patients not achieving remission and no association between uMCP-1 or uTWEAK with renal histological features.

Conclusion

Our study shows that uMCP-1 and uTWEAK are elevated in patients with active LN, correlated with the remission status (response to treatment) at the end of induction therapy and can, therefore, be useful for monitoring disease activity and treatment response.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

The datasets used and analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Wilhelmus S, Bajema IM, Bertsias GK, Boumpas DT, Gordon C, Lightstone L, Tesar V, Jayne DR (2016) Lupus nephritis management guidelines compared. Nephrol Dial Transplant 31(6):904–913. https://doi.org/10.1093/ndt/gfv102

    Article  PubMed  Google Scholar 

  2. Wadee S, Tikly M, Hopley M (2007) Causes and predictors of death in South Africans with systemic lupus erythematosus. Rheumatology (Oxford, England) 46(9):1487–1491. https://doi.org/10.1093/rheumatology/kem180

    Article  CAS  Google Scholar 

  3. Ayodele OE, Okpechi IG, Swanepoel CR (2010) Predictors of poor renal outcome in patients with biopsy-proven lupus nephritis. Nephrology 15(4):482–490

    Article  Google Scholar 

  4. Ayodele OE, Okpechi IG, Swanepoel CR (2013) Long-term renal outcome and complications in South Africans with proliferative lupus nephritis. Int UrolNephrol 45(5):1289–1300

    Google Scholar 

  5. Ameh OI, Kengne AP, Jayne D, Bello AK, Hodkinson B, Gcelu A, Okpechi IG (2016) Standard of treatment and outcomes of adults with lupus nephritis in Africa: a systematic review. Lupus. https://doi.org/10.1177/0961203316640915

    Article  PubMed  Google Scholar 

  6. Haladyj E, Cervera R (2016) Do we still need renal biopsy in lupus nephritis? Reumatologia 54(2):61–66. https://doi.org/10.5114/reum.2016.60214

    Article  PubMed  PubMed Central  Google Scholar 

  7. Nachman PH (2018) Repeat kidney biopsy for lupus nephritis: an important step forward. Kidney Int 94(4):659–661. https://doi.org/10.1016/j.kint.2018.06.026

    Article  PubMed  Google Scholar 

  8. Lateef A, Petri M (2012) Unmet medical needs in systemic lupus erythematosus. Arthritis Res Therapy 14(Suppl 4):S4. https://doi.org/10.1186/ar3919

    Article  Google Scholar 

  9. Medina-Rosas J, Su J, Cook RJ, Sabapathy A, Touma Z (2017) Comparison of spot urine protein to creatinine ratio to 24-hour proteinuria to identify important change over time in proteinuria in lupus. J ClinRheumatol: Practical Rep Rheumatic Musculoskeletal Dis 23(6):301–307. https://doi.org/10.1097/rhu.0000000000000557

    Article  Google Scholar 

  10. Soliman S, Mohan C (2017) Lupus nephritis biomarkers. ClinImmunol (Orlando, Fla) 185:10–20. https://doi.org/10.1016/j.clim.2016.08.001

    Article  CAS  Google Scholar 

  11. Xuejing Z, Jiazhen T, Jun L, Xiangqing X, Shuguang Y, Fuyou L (2012) Urinary TWEAK level as a marker of lupus nephritis activity in 46 cases. J Biomed Biotechnol 2012:359647. https://doi.org/10.1155/2012/359647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Taha H, Abdallah N, Salem M, Hamouda A, Abd Elazeem M, Eesa N (2017) Urinary and tissue monocyte chemoattractant protein1 (MCP1) in lupus nephritis patients. Egypt Rheumatol 39(3):145–150. https://doi.org/10.1016/j.ejr.2017.01.004

    Article  Google Scholar 

  13. Schwartz N, Su L, Burkly LC, Mackay M, Aranow C, Kollaros M, Michaelson JS, Rovin B, Putterman C (2006) Urinary TWEAK and the activity of lupus nephritis. J Autoimmun 27(4):242–250. https://doi.org/10.1016/j.jaut.2006.12.003

    Article  CAS  PubMed  Google Scholar 

  14. Lee YH, Song GG (2017) Urinary MCP-1 as a biomarker for lupus nephritis: a meta-analysis. Z Rheumatol 76(4):357–363. https://doi.org/10.1007/s00393-016-0109-z

    Article  CAS  PubMed  Google Scholar 

  15. Gao HX, Campbell SR, Burkly LC, Jakubowski A, Jarchum I, Banas B, Saleem MA, Mathieson PW, Berman JW, Michaelson JS, Putterman C (2009) TNF-like weak inducer of apoptosis (TWEAK) induces inflammatory and proliferative effects in human kidney cells. Cytokine 46(1):24–35. https://doi.org/10.1016/j.cyto.2008.12.001

    Article  CAS  PubMed  Google Scholar 

  16. Decker JL, Klippel JH, Plotz PH, Steinberg AD (1975) Cyclophosphamide or azathioprine in lupus glomerulonephritis. A controlled trial: results at 28 months. Ann Intern Med 83(5):606–615. https://doi.org/10.7326/0003-4819-83-5-606

    Article  CAS  PubMed  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 DD, Urowitz MB (1999) The SLICC/ACR damage index: progress report and experience in the field. Lupus 8(8):632–637. https://doi.org/10.1191/096120399680411335

    Article  CAS  PubMed  Google Scholar 

  19. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612

    Article  Google Scholar 

  20. Weening JJ, D’Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, Balow JE, Bruijn JA, Cook T, Ferrario F, Fogo AB, Ginzler EM, Hebert L, Hill G, Hill P, Jennette JC, Kong NC, Lesavre P, Lockshin M, Looi LM, Makino H, Moura LA, Nagata M (2004) The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int 65(2):521–530. https://doi.org/10.1111/j.1523-1755.2004.00443.x

    Article  PubMed  Google Scholar 

  21. Hill GS, Delahousse M, Nochy D, Tomkiewicz E, Remy P, Mignon F, Mery JP (2000) A new morphologic index for the evaluation of renal biopsies in lupus nephritis. Kidney Int 58(3):1160–1173. https://doi.org/10.1046/j.1523-1755.2000.00272.x

    Article  CAS  PubMed  Google Scholar 

  22. KDIGO (2012) Glomerulonephritis work group. KDIGO clinical practice guideline for glomerulonephritis. Kidney Int Suppl 2:139–274

    Article  Google Scholar 

  23. Sandhu V, Quan M (2017) SLE and serum complement: causative, concomitant or coincidental? Open Rheumatol J 11:113–122. https://doi.org/10.2174/1874312901711010113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Reyes-Thomas J, Blanco I, Putterman C (2011) Urinary biomarkers in lupus nephritis. Clin Rev Allergy Immunol 40(3):138–150. https://doi.org/10.1007/s12016-010-8197-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Suttichet TB, Kittanamongkolchai W, Phromjeen C, Anutrakulchai S, Panaput T, Ingsathit A, Kamanamool N, Ophascharoensuk V, Sumethakul V, Avihingsanon Y (2019) Urine TWEAK level as a biomarker for early response to treatment in active lupus nephritis: a prospective multicentre study. Lupus Sci Med 6(1):e000298. https://doi.org/10.1136/lupus-2018-000298

    Article  PubMed  PubMed Central  Google Scholar 

  26. Gigante A, Gasperini ML, Afeltra A, Barbano B, Margiotta D, Cianci R, De Francesco I, Amoroso A (2011) Cytokines expression in SLE nephritis. Eur Rev Med Pharmacol Sci 15(1):15–24

    CAS  PubMed  Google Scholar 

  27. Lu J, Hu ZB, Chen PP, Lu CC, Zhang JX, Li XQ, Yuan BY, Huang SJ, Ma KL (2019) Urinary podocyte microparticles are associated with disease activity and renal injury in systemic lupus erythematosus. BMC Nephrol 20(1):303. https://doi.org/10.1186/s12882-019-1482-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Perez-Hernandez J, Olivares MD, Forner MJ, Chaves FJ, Cortes R, Redon J (2016) Urinary dedifferentiated podocytes as a non-invasive biomarker of lupus nephritis. Nephrol Dial Transplant 31(5):780–789. https://doi.org/10.1093/ndt/gfw002

    Article  CAS  PubMed  Google Scholar 

  29. Zhao Z, Burkly LC, Campbell S, Schwartz N, Molano A, Choudhury A, Eisenberg RA, Michaelson JS, Putterman C (2007) TWEAK/Fn14 interactions are instrumental in the pathogenesis of nephritis in the chronic graft-versus-host model of systemic lupus erythematosus. J Immunol 179(11):7949–7958. https://doi.org/10.4049/jimmunol.179.11.7949

    Article  CAS  PubMed  Google Scholar 

  30. Tesar V, Hruskova Z (2015) Lupus nephritis: a different disease in european patients? Kidney Dis (Basel, Switzerland) 1(2):110–118. https://doi.org/10.1159/000438844

    Article  Google Scholar 

  31. Singh RG, Usha RSS, Behura SK, Singh NK (2012) Urinary MCP-1 as diagnostic and prognostic marker in patients with lupus nephritis flare. Lupus 21(11):1214–1218. https://doi.org/10.1177/0961203312452622

    Article  CAS  PubMed  Google Scholar 

  32. Schwartz N, Rubinstein T, Burkly LC, Collins CE, Blanco I, Su L, Hojaili B, Mackay M, Aranow C, Stohl W, Rovin BH, Michaelson JS, Putterman C (2009) Urinary TWEAK as a biomarker of lupus nephritis: a multicenter cohort study. Arthritis Res Therapy 11(5):R143. https://doi.org/10.1186/ar2816

    Article  CAS  Google Scholar 

  33. Dong X, Zheng Z, Luo X, Ding J, Li Y, Li Z, Li S, Rong M, Fu Y, Wu Z, Zhu P (2018) Combined utilization of untimed single urine of MCP-1 and TWEAK as a potential indicator for proteinuria in lupus nephritis: a case-control study. Medicine (Baltimore) 97(16):e0343. https://doi.org/10.1097/md.0000000000010343

    Article  CAS  Google Scholar 

Download references

Funding

This project was supported by grants from the South African National Research Fund (NRF) (CPRR150703122950).

Author information

Authors and Affiliations

Authors

Contributions

MWM, JAR, FO, DJ and IGO conceived the study. MWM, JAR, CD and IGO were involved in data collection, MWM, JAR, FO, UE, and IGO were involved in data analysis, writing up and interpretation, all authors were involved in revision of the manuscript for intellectual content. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Ikechi G. Okpechi.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Ethics approval and consent to participate

Ethics approval was obtained from the University of Cape Town Human Research Ethics Committee (HREC #332/2017). All participating patients provided signed consent form.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (XLSX 26 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Moloi, M.W., Rusch, J.A., Omar, F. et al. Urinary MCP-1 and TWEAK as non-invasive markers of disease activity and treatment response in patients with lupus nephritis in South Africa. Int Urol Nephrol 53, 1865–1873 (2021). https://doi.org/10.1007/s11255-020-02780-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-020-02780-9

Keywords

Navigation