Sage Journals: Discover world-class research

Abstract

Lupus nephritis (LN) is the leading cause of mortality in lupus patients. This study aimed to investigate the treatment outcome and renal histological risk factors of LN in a tertiary referral center. Between 2006 and 2017, a retrospective observational study enrolled 148 biopsy-proven LN patients. After propensity score matching, 75 cases were included for further analysis. The classification and scoring of LN were assessed according to the International Society of Nephrology/Renal Pathology Society. Treatment response was evaluated by daily urine protein and urinalysis at two years after commencing induction treatment and the development of end-stage renal disease (ESRD). In total, 50.7% patients achieved complete remission (CR) or partial remission (PR), while 49.3% patients were categorized as nonresponders. Therapeutic responses in terms of CR/PR rates were associated with Systemic Lupus Erythematosus Disease Activity Index scores (odds ratio (OR): 1.34, 95% confidence interval (CI): 1.12–1.60, p = 0.001). Moreover, higher baseline creatinine levels (hazard ratio (HR): 2.10, 95% CI: 1.29–3.40, p = 0.003), higher renal activity index (HR: 1.30, 95% CI: 1.07–1.58, p = 0.008) and chronicity index (HR: 1.40, 95% CI: 1.06–1.85, p = 0.017) predicted ESRD. Among pathological scores, cellular crescents (HR: 4.42, 95% CI: 1.01–19.38, p = 0.049) and fibrous crescents (HR: 5.93, 95% CI: 1.41–24.92, p = 0.015) were independent risk factors for ESRD. In conclusion, higher lupus activity was a good prognostic marker for renal remission. Renal histology was predictive of ESRD. Large-scale prospective studies are required to verify the efficacy of mycophenolate in combination with azathioprine or cyclosporine in LN patients.

Keywords

Induction therapy lupus nephritis remission systemic lupus erythematosus

Get full access to this article

View all access options for this article.

References

Bono

Cameron

Hicks

. The very long-term prognosis and complications of lupus nephritis and its treatment. QJM 1999; 92: 211–218.

Doria

Iaccarino

Ghirardello

et al.

Long-term prognosis and causes of death in systemic lupus erythematosus. Am J Med 2006; 119: 700–706.

Jakes

Bae

Louthrenoo

Mok

Navarra

Kwon

. Systematic review of the epidemiology of systemic lupus erythematosus in the Asia-Pacific region: Prevalence, incidence, clinical features, and mortality. Arthritis Care Res (Hoboken) 2012; 64: 159–168.

Osio-Salido

Manapat-Reyes

. Epidemiology of systemic lupus erythematosus in Asia. Lupus 2010; 19: 1365–1373.

Schwartz

Lan

Bonsib

Gephardt

Sharma

. Clinical outcome of three discrete histologic patterns of injury in severe lupus glomerulonephritis. Am J Kidney Dis 1989; 13: 273–283.

Leaker

Fairley

Dowling

Kincaid-Smith

. Lupus nephritis: Clinical and pathological correlation. Q J Med 1987; 62: 163–179.

Moroni

Pasquali

Quaglini

et al.

Clinical and prognostic value of serial renal biopsies in lupus nephritis. Am J Kidney Dis 1999; 34: 530–539.

Najafi

Korbet

Lewis

et al.

Significance of histologic patterns of glomerular injury upon long-term prognosis in severe lupus glomerulonephritis. Kidney Int 2001; 59: 2156–2163.

Korbet

Lewis

Schwartz

Reichlin

Evans

Rohde

. Factors predictive of outcome in severe lupus nephritis. Lupus Nephritis Collaborative Study Group. Am J Kidney Dis 2000; 35: 904–914.

10.

Fiehn

Hajjar

Mueller

Waldherr

Andrassy

. Improved clinical outcome of lupus nephritis during the past decade: Importance of early diagnosis and treatment. Ann Rheum Dis 2003; 62: 435–439.

11.

Faurschou

Starklint

Halberg

Jacobsen

. Prognostic factors in lupus nephritis: Diagnostic and therapeutic delay increases the risk of terminal renal failure. J Rheumatol 2006; 33: 1563–1569.

12.

Yap

Chan

. Lupus nephritis in Asia: Clinical features and management. Kidney Dis (Basel) 2015; 1: 100–109.

13.

Sprangers

Monahan

Appel

. Diagnosis and treatment of lupus nephritis flares—an update. Nat Rev Nephrol 2012; 8: 709–717.

14.

Chan

Tang

et al.

Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou Nephrology Study Group. N Engl J Med 2000; 343: 1156–1162.

15.

Zavada

Pesickova

Rysava

et al.

Cyclosporine A or intravenous cyclophosphamide for lupus nephritis: The Cyclofa-Lune study. Lupus 2010; 19: 1281–1289.

16.

Kamijo

Hashimoto

Takahashi

Ehara

Shigematsu

Higuchi

. Treatment with cyclosporine A improves SLE disease activity of Japanese patients with diffuse proliferative lupus nephritis. Clin Nephrol 2011; 76: 136–143.

17.

Tanaka

Oki

Tsugawa

Nonaka

Suzuki

Ito

. Effective treatment of young patients with pediatric-onset, long-standing lupus nephritis with tacrolimus given as a single daily dose: An open-label pilot study. Lupus 2007; 16: 896–900.

18.

Liu

Zhang

Liu

et al.

Multitarget therapy for induction treatment of lupus nephritis: A randomized trial. Ann Intern Med 2015; 162: 18–26.

19.

Mok

Ying

Yim

et al.

Tacrolimus versus mycophenolate mofetil for induction therapy of lupus nephritis: A randomised controlled trial and long-term follow-up. Ann Rheum Dis 2016; 75: 30–36.

20.

Hochberg

. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 1997; 40: 1725–1725.

21.

Hansen

Bowers

. Covariate balance in simple, stratified and clustered comparative studies. Stat Sci 2008; 23: 219–235.

22.

Bertsias

Tektonidou

Amoura

et al.

The Joint European League Against Rheumatism and European Renal Association/European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis 2012; 71: 1771–1782.

23.

Petri

Bockenstedt

Colman

et al.

Serial assessment of glomerular filtration rate in lupus nephropathy. Kidney Int 1988; 34: 832–839.

24.

Bombardier

Gladman

Urowitz

Caron

Chang

. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 1992; 35: 630–640.

25.

Weening

D’Agati

Schwartz

et al . The classification of glomerulonephritis in systemic lupus erythematosus revised. J Am Soc Nephrol 2004; 15: 241–250.

26.

Austin

3rd Boumpas

Vaughman

Balow

. Predicting renal outcome in severe lupus nephritis: Contributions of clinical and histologic data. Kidney Int 1994; 45: 544–550.

27.

Hahn

McMahon

Wilkinson

et al.

American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken) 2012; 64: 797–808.

28.

Zhang

Liu

Zhou

et al.

Multitarget therapy for maintenance treatment of lupus nephritis. J Am Soc Nephrol 2017; 28: 3671–3678.

29.

Aragon

Chan

Lau

Tan

Yap

. Good outcomes with mycophenolate-cyclosporine-based induction protocol in children with severe proliferative lupus nephritis. Lupus 2010; 19: 965–973.

30.

Aragon

Resontoc

Chan

et al.

Long-term outcomes with multi-targeted immunosuppressive protocol in children with severe proliferative lupus nephritis. Lupus 2016; 25: 399–406.

31.

Kasitanon

Boripatkosol

Louthrenoo

. Response to combination of mycophenolate mofetil, cyclosporin A and corticosteroid treatment in lupus nephritis patients with persistent proteinuria. Int J Rheum Dis 2018; 21: 200–207.

32.

Jesus

Rodrigues

da Silva

JAP

Inês

. Multitarget therapy of mycophenolate mofetil and cyclosporine A for induction treatment of refractory lupus nephritis. Lupus 2018; 27: 1358–1362.

33.

Mok

Chan

Lau

Wong

. Outcome and prognostic indicators of diffuse proliferative lupus glomerulonephritis treated with sequential oral cyclophosphamide and azathioprine. Arthritis Rheum 2002; 46: 1003–1013.

34.

Mok

Ying

et al.

Long-term outcome of diffuse proliferative lupus glomerulonephritis treated with cyclophosphamide. Am J Med 2006; 119: 355.e25–355.e33.

35.

Park

Choi

et al.

Chronicity index, especially glomerular sclerosis, is the most powerful predictor of renal response following immunosuppressive treatment in patients with lupus nephritis. Int J Rheum Dis 2018; 21: 458–467.

36.

Tang

Zhang

et al.

Clinicopathological and outcome analysis of adult lupus nephritis patients in China. Int Urol Nephrol 2015; 47: 513–520.

37.

Tektonidou

Dasgupta

Ward

. Risk of end-stage renal disease in patients with lupus nephritis, 1971–2015: A systematic review and Bayesian meta-analysis. Arthritis Rheumatol 2016; 68: 1432–1441.

38.

Davidson

et al.

Renal remission status and longterm renal survival in patients with lupus nephritis: A retrospective cohort analysis. J Rheumatol 2018; 45: 671–677.

39.

Hanaoka

Kiyokawa

Iida

et al.

Comparison of renal response to four different induction therapies in Japanese patients with lupus nephritis class III or IV: A single-centre retrospective study. PLoS One 2017; 12: e0175152–e0175152.

40.

Joo

Kang

Kim

et al.

Outcome and predictors of renal survival in patients with lupus nephritis: Comparison between cyclophosphamide and mycophenolate mofetil. Int J Rheum Dis 2018; 21: 1031–1039.

41.

Chen

Tang

Zhang

Liu

. Prediction of renal outcomes in patients with crescentic lupus nephritis. Am J Med Sci 2015; 349: 298–305.

42.

Moroni

Vercelloni

Quaglini

et al.

Changing patterns in clinical-histological presentation and renal outcome over the last five decades in a cohort of 499 patients with lupus nephritis. Ann Rheum Dis 2018; 77: 1318–1325.

43.

Ichinose

Kitamura

Sato

et al.

Factors predictive of long-term mortality in lupus nephritis: A multicenter retrospective study of a Japanese cohort. Lupus 2019; 28: 295–303.

44.

Norby

Mjøen

Bjørneklett

et al.

Outcome in biopsy-proven lupus nephritis: Evaluation of biopsies from the Norwegian Kidney Biopsy Registry. Lupus 2017; 26: 881–885.

45.

Zandman-Goddard

Shoenfeld

. Infections and SLE. Autoimmunity 2005; 38: 473–485.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.53 MB

Combination immunosuppressant therapy and lupus nephritis outcome: a hospital-based study

Abstract

Keywords

Get full access to this article

References

Supplementary Material