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Is serum uric acid a predictor of long-term renal outcome in lupus nephritis?

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Abstract

Background/objective

Recent studies observed an association between increased serum uric acid (SUA) levels and renal damage in lupus. However, the predictive value of UA for the development of long-term renal dysfunction in lupus nephritis (LN) is still unknown. The aim of this study was to evaluate if SUA may be a predictor of long-term renal outcome in LN.

Methods

Eighty biopsy-proven LN patients > 7 years of follow-up were selected. SUA levels were measured in sera stored at − 70 °C. All patients had serum stored from LN baseline, and 32 also had stored serum from 6 and 12 months after LN. Renal outcome was addressed after 7 years of follow-up to determine if SUA could be a predictor of long-term renal outcome. A good long-term renal outcome in 7 years was defined as a creatinine clearance (CrCl) ≥ 90.0 mL/min/1.73 m2, and poor if CrCl < 90 mL/min/1.73 m2. Patients were divided in two groups according to the renal outcome to assess whether SUA levels at different time points of follow-up could differentiate such groups. An ROC curve was plotted to assess accuracy.

Results

SUA levels at baseline and 6 months were not able to differentiate good from poor long-term renal outcomes in LN (respectively p = 0.37, p = 0.28), but at 12 months (p = 0.02), they could clearly differentiate the two groups. ROC curve (12 months) accuracy was 0.76. SUA cutoff was 6.05 mg/dL (sensitivity = 0.67, specificity = 0.89, positive predictive value = 0.85, negative predictive value = 0.73).

Conclusion

SUA levels < 6.05 mg/dL at 12 months of follow-up is a predictor of good long-term renal outcome in lupus nephritis.

Key Points

• Previous studies reported an association between increased serum uric acid level and short-term renal damage in lupus patients.

• The predictive value of serum uric acid for the development of long-term renal dysfunction in lupus nephritis was never assessed.

• At 12 months of follow-up serum uric acid clearly differentiated good from poor long-term renal outcome in lupus nephritis.

• SUA level < 6.05 mg/dL at 12 months of follow-up was a predictor of good long-term renal outcome in lupus nephritis.

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References

  1. 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, Lam MF, Chan TM (2017) Serum uric acid levels contribute to new renal damage in systemic lupus erythematosus patients. Clin Rheumatol 36(4):845–852. https://doi.org/10.1007/s10067-017-3538-4

    Article  PubMed  Google Scholar 

  2. Yap DY, Tang CS, Ma MK, Lam MF, Chan TM (2012) Survival analysis and causes of mortality in patients with lupus nephritis. Nephrol Dial Transplant 27(8):3248–3254. https://doi.org/10.1093/ndt/gfs073

    Article  PubMed  Google Scholar 

  3. Liu S, Gong Y, Ren H, Zhang W, Chen X, Zhou T, Li X, Chen N (2017) The prevalence, subtypes and associated factors of hyperuricemia in lupus nephritis patients at chronic kidney disease stages 1-3. Oncotarget. 8(34):57099–57108. https://doi.org/10.18632/oncotarget.19051.eCollection2017

  4. Calich AL, Borba EF, Ugolini-Lopes MR, da Rocha LF, 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. https://doi.org/10.1007/s10067-018-3991-8

    Article  PubMed  Google Scholar 

  5. Liu H, Cai X, Dai L, Ma J, Mo Y (2018) Elevated uric acid levels in premenopausal female systemic lupus erythematosus patients: association with potential or existing renal damage. Eur J Inflamm 16:1–6. sagepub.com/journals-permissions. journals.sagepub.com/home/eji. https://doi.org/10.1177/2058739218802442

    Article  Google Scholar 

  6. Bomback AS, Appel GB (2010) Updates on the treatment of lupus nephritis. J Am Soc Nephrol 21:2028–2035. https://doi.org/10.1681/ASN.2010050472

    Article  CAS  PubMed  Google Scholar 

  7. Majdan M (2015) Treat-to-target in rheumatology. Wiad Lek 68:259–264

    PubMed  Google Scholar 

  8. Van Vollenhoven RF, Mosca M, Bertsias G, van Vollenhoven RF, Mosca M, Bertsias G, Isenberg D, Kuhn A, Lerstrøm K, Aringer M, Bootsma H, Boumpas D, Bruce IN, Cervera R, Clarke A, Costedoat-Chalumeau N, Czirják L, Derksen R, Dörner T, Gordon C, Graninger W, Houssiau F, Inanc M, Jacobsen S, Jayne D, Jedryka-Goral A, Levitsky A, Levy R, Mariette X, Morand E, Navarra S, Neumann I, Rahman A, Rovensky J, Smolen J, Vasconcelos C, Voskuyl A, Voss A, Zakharova H, Zoma A, Schneider M (2014) Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. Ann Rheum Dis 73:958–967. https://doi.org/10.1136/annrheumdis-2013-205139

    Article  PubMed  Google Scholar 

  9. Tamirou F, Lauwerys BR, Dall'Era M, Mackay M, Rovin B, Cervera R, Houssiau FA, Nephritis Trial Investigators MAINTAIN (2015) A proteinuria cut-off level of 0.7 g/day after 12 months of treatment best predicts long-term renal outcome in lupus nephritis: data from the MAINTAIN Nephritis Trial. Lupus Sci Med 2(1):e000123. https://doi.org/10.1136/lupus-2015-000123 eCollection 2015

    Article  PubMed  PubMed Central  Google Scholar 

  10. Dall'Era M, Cisternas MG, Smilek DE, Straub L, Houssiau FA, Cervera R, Rovin BH, Mackay M (2015) Predictors of long-term renal outcome in lupus nephritis trials: lessons learned from the Euro-Lupus Nephritis cohort. Arthritis Rheum 67:1305–1313. https://doi.org/10.1002/art.39026

    Article  CAS  Google Scholar 

  11. Ugolini-Lopes MR, Seguro LPC, Castro MXF, Daffre D, Lopes AC, Borba EF, Bonfá E (2017) Early proteinuria response: a valid real-life situation predictor of long-term lupus renal outcome in an ethnically diverse group with severe biopsy-proven nephritis? Lupus Sci Med 4(1):e000213. https://doi.org/10.1136/lupus-2017-000213 . eCollection 2017

    Article  PubMed  PubMed Central  Google Scholar 

  12. Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR, Bruce IN, Isenberg D, Wallace DJ, Nived O, Sturfelt G, Ramsey-Goldman R, Bae SC, Hanly JG, Sánchez-Guerrero J, Clarke A, Aranow C, Manzi S, Urowitz M, Gladman D, Kalunian K, Costner M, Werth VP, Zoma A, Bernatsky S, Ruiz-Irastorza G, Khamashta MA, Jacobsen S, Buyon JP, Maddison P, Dooley MA, van Vollenhoven RF, Ginzler E, Stoll T, Peschken C, Jorizzo JL, Callen JP, Lim SS, Fessler BJ, Inanc M, Kamen DL, Rahman A, Steinsson K, Franks AG Jr, Sigler L, Hameed S, Fang H, Pham N, Brey R, Weisman MH, McGwin G Jr, Magder LS (2012) Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 64(8):2677–2686. https://doi.org/10.1002/art.34473

    Article  PubMed  PubMed Central  Google Scholar 

  13. Levey AS, Coresh J, Balk E, Kausz AT, Levin A, Steffes MW, Hogg RJ, Perrone RD, Lau J, Eknoyan G, National Kidney Foundation (2003) National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 139:137–147

    Article  PubMed  Google Scholar 

  14. Giannico G, Fogo AB (2013) Lupus nephritis: is the kidney biopsy currently necessary in the management of lupus nephritis? Clin J Am Soc Nephrol 8(1):138–145. https://doi.org/10.2215/CJN.03400412

    Article  PubMed  Google Scholar 

  15. Houssiau FA, Vasconcelos C, D'Cruz D, Sebastiani GD, Garrido Ed Ede R, Danieli MG, Abramovicz D, Blockmans D, Mathieu A, Direskeneli H, Galeazzi M, Gül A, Levy Y, Petera P, Popovic R, Petrovic R, Sinico RA, Cattaneo R, Font J, Depresseux G, Cosyns JP, Cervera R (2002) Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum 46:2121–2131. https://doi.org/10.1002/art.10461

    Article  CAS  PubMed  Google Scholar 

  16. Boumpas DT, Austin HA 3rd, Vaughn EM, Klippel JH, Steinberg AD, Yarboro CH, Balow JE (1992) Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis. Lancet. 340(8822):741–745

    Article  CAS  PubMed  Google Scholar 

  17. Appel GB, Cohen DJ, Pirani CL, Meltzer JI, Estes D (1987) Long-term follow-up of patients with lupus nephritis. A study based on the classification of the World Health Organization. Am J Med 83:877–885

    Article  CAS  PubMed  Google Scholar 

  18. Moroni G, Quaglini S, Maccario M, Banfi G, Ponticelli C (1996) "Nephritic flares" are predictors of bad long-term renal outcome in lupus nephritis. Kidney Int 50(6):2047–2053

    Article  CAS  PubMed  Google Scholar 

  19. Cuhadar S, Atay A, Koseoglu M, Dirican A, Hur A (2012) Stability studies of common biochemical analytes in serum separator tubes with or without gel barrier subjected to various storage conditions. Biochem Med (Zagreb) 22(2):202–214

    Article  CAS  Google Scholar 

  20. Cuhadar S, Koseoglu M, Atay A, Dirican A (2013) The effect of storage time and freeze-thaw cycles on the stability of serum samples. Biochem Med (Zagreb) 23(1):70–77

    Article  CAS  Google Scholar 

  21. Kachhawa K, Kachhawa P, Varma M, Behera R, Agrawal D, Kumar S (2017) Study of the stability of various biochemical analytes in samples stored at different predefined storage conditions at an accredited laboratory of India. J Lab Physicians 9(1):11–15. https://doi.org/10.4103/0974-2727.187928

    Article  PubMed  PubMed Central  Google Scholar 

  22. Martínez-Martínez MU, Borjas-García JA, Magaña-Aquino M, Cuevas-Orta E, Llamazares-Azuara L, Abud-Mendoza C (2012) Renal function assessment in patients with systemic lupus erythematosus. Rheumatol Int 32(8):2293–2299. https://doi.org/10.1007/s00296-011-1940-9

    Article  PubMed  Google Scholar 

  23. Collaborative Study Group, Korbet SM, Whittier WL, Lewis EJ (2016) The impact of baseline serum creatinine on complete remission rate and long-term outcome in patients with severe lupus nephritis. Nephron Extra 6(2):12–21. https://doi.org/10.1159/000448487

    Article  Google Scholar 

  24. McQuarrie EP, Traynor JP, Taylor AH, Freel EM, Fox JG, Jardine AG, Mark PB (2014) Association between urinary sodium, creatinine, albumin, and long-term survival in chronic kidney disease. Hypertension. 64(1):111–117. https://doi.org/10.1161/HYPERTENSIONAHA.113.03093

    Article  CAS  PubMed  Google Scholar 

  25. Feig DI (2014) Serum uric acid and the risk of hypertension and chronic kidney disease. Curr Opin Rheumatol 26(2):176–185. https://doi.org/10.1097/BOR.0000000000000033

    Article  CAS  PubMed  Google Scholar 

  26. 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 15:122. https://doi.org/10.1186/1471-2369-15-122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hsieh YP, Chang CC, Yang Y, Wen YK, Chiu PF, Lin CC (2017) The role of uric acid in chronic kidney disease patients. Nephrology (Carlton) 22(6):441–448. https://doi.org/10.1111/nep.12679

    Article  CAS  Google Scholar 

  28. Kang DH, Nakagawa T, Feng L, Watanabe S, Han L, Mazzali M, Truong L, Harris R, Johnson RJ (2002) A role for uric acid in the progression of renal disease. J Am Soc Nephrol 13(12):2888–2897

    Article  CAS  PubMed  Google Scholar 

  29. Kang DH, Nakagawa T (2005) Uric acid and chronic renal disease: possible implication of hyperuricemia on progression of renal disease. Semin Nephrol 25(1):43–49

    Article  CAS  PubMed  Google Scholar 

  30. Xie T, Chen M, Tang X, Yin H, Wang X, Li G, Li J, Zuo X, Zhang W (2016) Hyperuricemia is an independent risk factor for renal pathological damage and poor prognosis in lupus nephritis patients. Zhong Nan Da Xue Xue Bao Yi Xue Ban 41(10):1052–1057. https://doi.org/10.11817/j.issn.1672-7347.2016.10.007. Access Sept 2018

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

    Article  CAS  PubMed  Google Scholar 

  32. Feig DI, Kang DH, Johnson RJ (2008) Uric acid and cardiovascular risk. N Engl J Med 359(17):1811–1821. https://doi.org/10.1056/NEJMra0800885

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This study was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (#305068/2014-8 to EB and #307226/2014-0 to EFB).

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Authors and Affiliations

  1. Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Av. Dr. Arnaldo 455 – 3rd floor - Room 3190 CEP, São Paulo, SP, 1246-903, Brazil

    Michelle Remião Ugolini-Lopes, Samara S. Gavinier, Elaine Leon, Vilma Trindade Viana, Eduardo Ferreira Borba & Eloisa Bonfá

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  1. Michelle Remião Ugolini-Lopes
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Correspondence to Michelle Remião Ugolini-Lopes.

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The study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments and was approved by the Local Ethics committee.

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Ugolini-Lopes, M.R., Gavinier, S.S., Leon, E. et al. Is serum uric acid a predictor of long-term renal outcome in lupus nephritis?. Clin Rheumatol 38, 2777–2783 (2019). https://doi.org/10.1007/s10067-019-04620-3

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