Original Research
6 January 2015

Multitarget Therapy for Induction Treatment of Lupus Nephritis: A Randomized Trial

Publication: Annals of Internal Medicine
Volume 162, Number 1

Abstract

Background:

Treatment of lupus nephritis (LN) remains challenging.

Objective:

To assess the efficacy and safety of a multitarget therapy consisting of tacrolimus, mycophenolate mofetil, and steroid compared with intravenous cyclophosphamide and steroid as induction therapy for LN.

Design:

24-week randomized, open-label, multicenter study. (ClinicalTrials.gov: NCT00876616)

Setting:

26 renal centers in China.

Patients:

Adults (aged 18 to 65 years) with biopsy-proven LN.

Intervention:

Tacrolimus, 4 mg/d, and mycophenolate mofetil, 1.0 g/d, versus intravenous cyclophosphamide with a starting dose of 0.75 (adjusted to 0.5 to 1.0) g/m2 of body surface area every 4 weeks for 6 months. Both groups received 3 days of pulse methylprednisolone followed by a tapering course of oral prednisone therapy.

Measurements:

The primary end point was complete remission at 24 weeks. Secondary end points included overall response (complete and partial remission), time to overall response, and adverse events.

Results:

After 24 weeks of therapy, more patients in the multitarget group (45.9%) than in the intravenous cyclophosphamide group (25.6%) showed complete remission (difference, 20.3 percentage points [95% CI, 10.0 to 30.6 percentage points]; P  < 0.001). The overall response incidence was higher in the multitarget group than in the intravenous cyclophosphamide group (83.5% vs. 63.0%; difference, 20.4 percentage points [CI, 10.3 to 30.6 percentage points]; P < 0.001), and the median time to overall response was shorter in the multitarget group (difference, −4.1 weeks [CI, −7.9 to −2.1 weeks]). Incidence of adverse events did not differ between the multitarget and intravenous cyclophosphamide groups (50.3% [91 of 181] vs. 52.5% [95 of 181]).

Limitation:

The study was limited to 24 weeks of follow-up.

Conclusion:

Multitarget therapy provides superior efficacy compared with intravenous cyclophosphamide as induction therapy for LN.

Primary Funding Source:

National Basic Research Program of China, National Key Technology R&D Program.

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Supplemental Material

Supplement. Data supplement

References

1.
Chen YEKorbet SMKatz RSSchwartz MMLewis EJCollaborative Study Group. Value of a complete or partial remission in severe lupus nephritis. Clin J Am Soc Nephrol. 2008;3:46-53. [PMID: 18003764]
2.
Moroni GQuaglini SGallelli BBanfi GMessa PPonticelli C. The long-term outcome of 93 patients with proliferative lupus nephritis. Nephrol Dial Transplant. 2007;22:2531-9. [PMID: 17510096]
3.
Appel GBContreras GDooley MAGinzler EMIsenberg DJayne Det alAspreva Lupus Management Study Group. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol. 2009;20:1103-12. [PMID: 19369404]  doi: 10.1681/ASN.2008101028
4.
Ginzler EMDooley MAAranow CKim MYBuyon JMerrill JTet al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med. 2005;353:2219-28. [PMID: 16306519]
5.
Lu FTu YPeng XWang LWang HSun Zet alMMF in Induction Therapy for Active Lupus Nephritis in Mainland China Study Group. A prospective multicentre study of mycophenolate mofetil combined with prednisolone as induction therapy in 213 patients with active lupus nephritis. Lupus. 2008;17:622-9. [PMID: 18625634]  doi: 10.1177/0961203308089428
6.
Weng MYWeng CTLiu MF. The efficacy of low-dose mycophenolate mofetil for treatment of lupus nephritis in Taiwanese patients with systemic lupus erythematosus. Clin Rheumatol. 2010;29:771-5. [PMID: 20195879]  doi: 10.1007/s10067-010-1403-9
7.
Li XRen HZhang QZhang WWu XXu Yet al. Mycophenolate mofetil or tacrolimus compared with intravenous cyclophosphamide in the induction treatment for active lupus nephritis. Nephrol Dial Transplant. 2012;27:1467-72. [PMID: 21917733]  doi: 10.1093/ndt/gfr484
8.
Bao HLiu ZHXie HLHu WXZhang HTLi LS. Successful treatment of class V+IV lupus nephritis with multitarget therapy. J Am Soc Nephrol. 2008;19:2001-10. [PMID: 18596121]  doi: 10.1681/ASN.2007121272
9.
Bomback ASAppel GB. Updates on the treatment of lupus nephritis. J Am Soc Nephrol. 2010;21:2028-35. [PMID: 21051743]  doi: 10.1681/ASN.2010050472
10.
Ekberg HTedesco-Silva HDemirbas AVíitko SNashan BGürkan Aet alELITE-Symphony Study. Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med. 2007;357:2562-75. [PMID: 18094377]
11.
Ekberg HBernasconi CNöldeke JYussim AMjörnstedt LErken Uet al. Cyclosporine, tacrolimus and sirolimus retain their distinct toxicity profiles despite low doses in the Symphony study. Nephrol Dial Transplant. 2010;25:2004-10. [PMID: 20106825]  doi: 10.1093/ndt/gfp778
12.
Ekberg HvanGelder TKaplan BBernasconi C. Relationship of tacrolimus exposure and mycophenolate mofetil dose with renal function after renal transplantation. Transplantation. 2011;92:82-7. [PMID: 21562449]  doi: 10.1097/TP.0b013e31821fad06
13.
Dooley MAJayne DGinzler EMIsenberg DOlsen NJWofsy Det alALMS Group. Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N Engl J Med. 2011;365:1886-95. [PMID: 22087680]  doi: 10.1056/NEJMoa1014460v
14.
Dall'Era M. Mycophenolate mofetil in the treatment of systemic lupus erythematosus. Curr Opin Rheumatol. 2011;23:454-8. [PMID: 21720247]  doi: 10.1097/BOR.0b013e328349a1e5
15.
Faul CDonnelly MMerscher-Gomez SChang YHFranz SDelfgaauw Jet al. The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med. 2008;14:931-8. [PMID: 18724379]  doi: 10.1038/nm.1857
16.
Wang LChang JHPaik SYTang YEisner WSpurney RF. Calcineurin (CN) activation promotes apoptosis of glomerular podocytes both in vitro and in vivo. Mol Endocrinol. 2011;25:1376-86. [PMID: 21622531]  doi: 10.1210/me.2011-0029
17.
Szeto CCKwan BCLai FMTam LSLi EKChow KMet al. Tacrolimus for the treatment of systemic lupus erythematosus with pure class V nephritis. Rheumatology (Oxford). 2008;47:1678-81. [PMID: 18753192]  doi: 10.1093/rheumatology/ken335
18.
Austin HA 3rdIllei GGBraun MJBalow JE. Randomized, controlled trial of prednisone, cyclophosphamide, and cyclosporine in lupus membranous nephropathy. J Am Soc Nephrol. 2009;20:901-11. [PMID: 19297556]  doi: 10.1681/ASN.2008060665
19.
Lee YHLee HSChoi SJDaiJi JSong GG. Efficacy and safety of tacrolimus therapy for lupus nephritis: a systematic review of clinical trials. Lupus. 2011;20:636-40. [PMID: 21382917]  doi: 10.1177/0961203310389486
20.
Uchino ATsukamoto HNakashima HYoshizawa SFurugo IMitoma Het al. Tacrolimus is effective for lupus nephritis patients with persistent proteinuria. Clin Exp Rheumatol. 2010;28:6-12. [PMID: 20346231]
21.
Chen WTang XLiu QChen WFu PLiu Fet al. Short-term outcomes of induction therapy with tacrolimus versus cyclophosphamide for active lupus nephritis: A multicenter randomized clinical trial. Am J Kidney Dis. 2011;57:235-44. [PMID: 21177013]  doi: 10.1053/j.ajkd.2010.08.036
22.
Weening JJD'Agati VDSchwartz MMSeshan SVAlpers CEAppel GBet al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol. 2004;15:241-50. [PMID: 14747370]
23.
Chan TMLi FKTang CSWong RWFang GXJi YLet al. Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou Nephrology Study Group. N Engl J Med. 2000;343:1156-62. [PMID: 11036121]
24.
Ong LMHooi LSLim TOGoh BLAhmad GGhazalli Ret al. Randomized controlled trial of pulse intravenous cyclophosphamide versus mycophenolate mofetil in the induction therapy of proliferative lupus nephritis. Nephrology (Carlton). 2005;10:504-10. [PMID: 16221103]
25.
Little RJD'Agostino RCohen MLDickersin KEmerson SSFarrar JTet al. The prevention and treatment of missing data in clinical trials. N Engl J Med. 2012;367:1355-60. [PMID: 23034025]  doi: 10.1056/NEJMsr1203730
26.
Localio ARBerlin JATen Have TRKimmel SE. Adjustments for center in multicenter studies: an overview. Ann Intern Med. 2001;135:112-23. [PMID: 11453711]
27.
Kulkarni OPAnders HJ. Lupus nephritis. How latest insights into its pathogenesis promote novel therapies. Curr Opin Rheumatol. 2012;24:457-65. [PMID: 22810362]  doi: 10.1097/BOR.0b013e328354c877
28.
Yap DYYu XChen XMLu FChen NLi XWet al. Pilot 24 month study to compare mycophenolate mofetil and tacrolimus in the treatment of membranous lupus nephritis with nephrotic syndrome. Nephrology (Carlton). 2012;17:352-7. [PMID: 22295934]  doi: 10.1111/j.1440-1797.2012.01574.x
29.
Wang HYCui TGHou FFNi ZHChen XMLu FMet alChina Leflunomide Lupus Nephritis Study Group. Induction treatment of proliferative lupus nephritis with leflunomide combined with prednisone: a prospective multi-centre observational study. Lupus. 2008;17:638-44. [PMID: 18625636]  doi: 10.1177/0961203308089408
30.
Korbet SMSchwartz MMEvans JLewis EJCollaborative Study Group. Severe lupus nephritis: racial differences in presentation and outcome. J Am Soc Nephrol. 2007;18:244-54. [PMID: 17167111]
31.
Isenberg DAppel GBContreras GDooley MAGinzler EMJayne Det al. Influence of race/ethnicity on response to lupus nephritis treatment: the ALMS study. Rheumatology (Oxford). 2010;49:128-40. [PMID: 19933596]  doi: 10.1093/rheumatology/kep346
32.
Daleboudt GMBajema IMGoemaere NNvan Laar JMBruijn JABerger SP. The clinical relevance of a repeat biopsy in lupus nephritis flares. Nephrol Dial Transplant. 2009;24:3712-7. [PMID: 19622571]  doi: 10.1093/ndt/gfp359
33.
Rice J. Mathematical Statistics and Data Analysis. 3rd ed. Belmont, CA: Duxbury; 2007.
34.
Hedeker DGibbons RD. Application of random-effects pattern-mixture models for missing data in longitudinal studies. Psychological Methods. 1997;2:64-78.
35.
Pickles ACrouchley R. A comparison of frailty models for multivariate survival data. Stat Med. 1995;14:1447-61. [PMID: 7481183]
36.
Hougaard P. Frailty models for survival data. Lifetime Data Anal. 1995;1:255-73. [PMID: 9385105]
37.
MacFarlane GDScheller DGErsfeld DLShaw LMVenkatarmanan RSarkozi Let al. Analytical validation of the PRO-Trac II ELISA for the determination of tacrolimus (FK506) in whole blood. Clin Chem. 1999;45:1449-58. [PMID: 10471647]
38.
Shaw LMNicholls AHale MArmstrong VWOellerich MYatscoff Ret al. Therapeutic monitoring of mycophenolic acid. A consensus panel report. Clin Biochem. 1998;31:317-22. [PMID: 9721428]
39.
Austin HA 3rdMuenz LRJoyce KMAntonovych TAKullick MEKlippel JHet al. Prognostic factors in lupus nephritis. Contribution of renal histologic data. Am J Med. 1983;75:382-91. [PMID: 6351607]
40.
Austin HA 3rdBoumpas DTVaughan EMBalow JE. Predicting renal outcomes in severe lupus nephritis: contributions of clinical and histologic data. Kidney Int. 1994;45:544-50. [PMID: 8164443]
41.
Austin HA 3rdMuenz LRJoyce KMAntonovych TTBalow JE. Diffuse proliferative lupus nephritis: identification of specific pathologic features affecting renal outcome. Kidney Int. 1984;25:689-95. [PMID: 6482173]

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Alexandre Braga Libório, Dulce Maria Silva Barreto5 December 2014
Comment
We read with interest the article by Liu et al. [1] evaluating a multitarget therapy for induction treatment of lupus nephritis. In this article, the authors conclude that patients receiving triple therapy (prednisone, mycophenolate and tacrolimus) achieved more complete remission than patients receiving prednisone and cyclophosphamide alone. Complete remission criteria utilized by the authors include renal function, urine sediment, serum albumin and 24h-proteinuria. At appendix table 5, it is clear that multitarget therapy was better regarding proteinuria reduction, but not in relation to renal function. In fact, there was a greater renal function improvement in the cyclophosphamide-treated group (although non-statistically significant). Some questions remain about the results: (1) taking into consideration only nephritic remission criteria (renal function and urinary sediment), was there any difference between the groups?; (2) if only proteinuria remission was responsible for the difference between the groups, how many patients received angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-II receptor blocker (ARB)? Moreover, we believe that systematic use of ACEI/ARB must be part of a treatment protocol when evaluating a drug with possible immunosuppressive-independent antiproteinuric action such as calcineurin inhibitor.
The authors declare no potential conflict of interest.

1. Liu, Z., Zhang, H., Liu, Z., Xing, C., Fu, P., Ni, Z., Chen, J., Lin, H., Liu, F., He, Y., He, Y., Miao, L., Chen, N., Li, Y., Gu, Y., Shi, W., Hu, W., Liu, Z., Bao, H., Zeng, C. & Zhou, M., 2014, Multitarget Therapy for Induction Treatment of Lupus Nephritis: A Randomized, Controlled Trial, Annals of internal medicine.

Alexandre Braga Libório*
Dulce Maria Silva Barreto#
* Professor, Clinical Medicine Department, Universidade Federal do Ceará,
# Chief of Glomerulopathy Section, Nephrology service, Hospital Geral de Fortaleza.
Y.K.O. Teng, T.W.J. Huizinga, A.J. Rabelink22 December 2014
Comment on Multitarget therapy in Lupus Nephritis
We read with interest the article of Zhihong et al. in which they compared triple therapy with cellcept, tacrolimus and steroids to monthly cyclophosphamide. The authors included patients of Asian origin with new-onset lupus nephritis or a flare while on azathioprine maintenance therapy. Patients were included from 2009-2011 and the 24-weeks results are described which are in favor of triple therapy.
As this study stopped including patients 3,5 years ago, it is of highly interest for the practicing clinician to know what maintenance therapy was given. We know from kidney transplantation literature that calcineurin-induced (CNI) nephrotoxicity was found in 25% of patients after 24 weeks, 33% after 1 year and almost 100% after 10 year (NEJM 2003;349:2326). Because the authors were able to analyse 23 repeat biopsies, it would be interesting to establish microscopic signs of CNI nephrotoxicity which would explain the lower eGFR in the multitarget treatment group.
Whether multitarget therapy is really superior to high dose cyclophosphamide will need to be proven when further follow-up of the study is shared. The present study was designed as a non-superiority trial with an estimated power of 80% and the hypothetical power of superiority of multitarget therapy was not calculated. From a statistical point of view, there was a 14% drop-out in each group which was not reflected in the statistical non-responder analysis. Despite this, the present study shows very promising results and definitely warrants further study in a general (non-Asian) lupus nephritis population. Because the follow-up was short, and, as with any successful induction therapy in lupus nephritis, two questions remain unsolved: how long and how intense should this therapy be given in order to achieve long-term remission without cumulative side-effects?

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Information

Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 162Number 16 January 2015
Pages: 18 - 26

History

Published online: 6 January 2015
Published in issue: 6 January 2015

Keywords

Authors

Affiliations

Zhihong Liu, MD
From Jinling Hospital, Nanjing University School of Medicine and The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; West China Hospital, Chengdu, China; Renji Hospital, Ruijin Hospital, and Huashan Hospital, Shanghai, China; The First Affiliated Hospital of Zhejiang University, Hangzhou, China; The First Affiliated Hospital of Dalian Medical University, Dalian, China;
The Second Xiangya Hospital of Central South University, Changsha, China; Shenzhen Second People's Hospital, Shenzhen, China; Daping Hospital, Chongqing, China; The Second Affiliated Hospital of Jilin University, Changchun, China; The Third Hospital of Hebei Medical University, Hebei, China; and Guangdong General Hospital, Guangdong, China.
Haitao Zhang, MD
From Jinling Hospital, Nanjing University School of Medicine and The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; West China Hospital, Chengdu, China; Renji Hospital, Ruijin Hospital, and Huashan Hospital, Shanghai, China; The First Affiliated Hospital of Zhejiang University, Hangzhou, China; The First Affiliated Hospital of Dalian Medical University, Dalian, China;
The Second Xiangya Hospital of Central South University, Changsha, China; Shenzhen Second People's Hospital, Shenzhen, China; Daping Hospital, Chongqing, China; The Second Affiliated Hospital of Jilin University, Changchun, China; The Third Hospital of Hebei Medical University, Hebei, China; and Guangdong General Hospital, Guangdong, China.
Zhangsuo Liu, MD
From Jinling Hospital, Nanjing University School of Medicine and The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; West China Hospital, Chengdu, China; Renji Hospital, Ruijin Hospital, and Huashan Hospital, Shanghai, China; The First Affiliated Hospital of Zhejiang University, Hangzhou, China; The First Affiliated Hospital of Dalian Medical University, Dalian, China;
The Second Xiangya Hospital of Central South University, Changsha, China; Shenzhen Second People's Hospital, Shenzhen, China; Daping Hospital, Chongqing, China; The Second Affiliated Hospital of Jilin University, Changchun, China; The Third Hospital of Hebei Medical University, Hebei, China; and Guangdong General Hospital, Guangdong, China.
Changying Xing, PhD
From Jinling Hospital, Nanjing University School of Medicine and The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; West China Hospital, Chengdu, China; Renji Hospital, Ruijin Hospital, and Huashan Hospital, Shanghai, China; The First Affiliated Hospital of Zhejiang University, Hangzhou, China; The First Affiliated Hospital of Dalian Medical University, Dalian, China;
The Second Xiangya Hospital of Central South University, Changsha, China; Shenzhen Second People's Hospital, Shenzhen, China; Daping Hospital, Chongqing, China; The Second Affiliated Hospital of Jilin University, Changchun, China; The Third Hospital of Hebei Medical University, Hebei, China; and Guangdong General Hospital, Guangdong, China.
Ping Fu, MD
From Jinling Hospital, Nanjing University School of Medicine and The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; West China Hospital, Chengdu, China; Renji Hospital, Ruijin Hospital, and Huashan Hospital, Shanghai, China; The First Affiliated Hospital of Zhejiang University, Hangzhou, China; The First Affiliated Hospital of Dalian Medical University, Dalian, China;
The Second Xiangya Hospital of Central South University, Changsha, China; Shenzhen Second People's Hospital, Shenzhen, China; Daping Hospital, Chongqing, China; The Second Affiliated Hospital of Jilin University, Changchun, China; The Third Hospital of Hebei Medical University, Hebei, China; and Guangdong General Hospital, Guangdong, China.
Zhaohui Ni, MD
From Jinling Hospital, Nanjing University School of Medicine and The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; West China Hospital, Chengdu, China; Renji Hospital, Ruijin Hospital, and Huashan Hospital, Shanghai, China; The First Affiliated Hospital of Zhejiang University, Hangzhou, China; The First Affiliated Hospital of Dalian Medical University, Dalian, China;
The Second Xiangya Hospital of Central South University, Changsha, China; Shenzhen Second People's Hospital, Shenzhen, China; Daping Hospital, Chongqing, China; The Second Affiliated Hospital of Jilin University, Changchun, China; The Third Hospital of Hebei Medical University, Hebei, China; and Guangdong General Hospital, Guangdong, China.
Jianghua Chen, MD
From Jinling Hospital, Nanjing University School of Medicine and The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; West China Hospital, Chengdu, China; Renji Hospital, Ruijin Hospital, and Huashan Hospital, Shanghai, China; The First Affiliated Hospital of Zhejiang University, Hangzhou, China; The First Affiliated Hospital of Dalian Medical University, Dalian, China;
The Second Xiangya Hospital of Central South University, Changsha, China; Shenzhen Second People's Hospital, Shenzhen, China; Daping Hospital, Chongqing, China; The Second Affiliated Hospital of Jilin University, Changchun, China; The Third Hospital of Hebei Medical University, Hebei, China; and Guangdong General Hospital, Guangdong, China.
Hongli Lin, MD
From Jinling Hospital, Nanjing University School of Medicine and The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; West China Hospital, Chengdu, China; Renji Hospital, Ruijin Hospital, and Huashan Hospital, Shanghai, China; The First Affiliated Hospital of Zhejiang University, Hangzhou, China; The First Affiliated Hospital of Dalian Medical University, Dalian, China;
The Second Xiangya Hospital of Central South University, Changsha, China; Shenzhen Second People's Hospital, Shenzhen, China; Daping Hospital, Chongqing, China; The Second Affiliated Hospital of Jilin University, Changchun, China; The Third Hospital of Hebei Medical University, Hebei, China; and Guangdong General Hospital, Guangdong, China.
Fuyou Liu, MD
From Jinling Hospital, Nanjing University School of Medicine and The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; West China Hospital, Chengdu, China; Renji Hospital, Ruijin Hospital, and Huashan Hospital, Shanghai, China; The First Affiliated Hospital of Zhejiang University, Hangzhou, China; The First Affiliated Hospital of Dalian Medical University, Dalian, China;
The Second Xiangya Hospital of Central South University, Changsha, China; Shenzhen Second People's Hospital, Shenzhen, China; Daping Hospital, Chongqing, China; The Second Affiliated Hospital of Jilin University, Changchun, China; The Third Hospital of Hebei Medical University, Hebei, China; and Guangdong General Hospital, Guangdong, China.
Yongcheng He, MD
From Jinling Hospital, Nanjing University School of Medicine and The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; West China Hospital, Chengdu, China; Renji Hospital, Ruijin Hospital, and Huashan Hospital, Shanghai, China; The First Affiliated Hospital of Zhejiang University, Hangzhou, China; The First Affiliated Hospital of Dalian Medical University, Dalian, China;
The Second Xiangya Hospital of Central South University, Changsha, China; Shenzhen Second People's Hospital, Shenzhen, China; Daping Hospital, Chongqing, China; The Second Affiliated Hospital of Jilin University, Changchun, China; The Third Hospital of Hebei Medical University, Hebei, China; and Guangdong General Hospital, Guangdong, China.
Yani He, MD
From Jinling Hospital, Nanjing University School of Medicine and The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; West China Hospital, Chengdu, China; Renji Hospital, Ruijin Hospital, and Huashan Hospital, Shanghai, China; The First Affiliated Hospital of Zhejiang University, Hangzhou, China; The First Affiliated Hospital of Dalian Medical University, Dalian, China;
The Second Xiangya Hospital of Central South University, Changsha, China; Shenzhen Second People's Hospital, Shenzhen, China; Daping Hospital, Chongqing, China; The Second Affiliated Hospital of Jilin University, Changchun, China; The Third Hospital of Hebei Medical University, Hebei, China; and Guangdong General Hospital, Guangdong, China.
Lining Miao, MD
From Jinling Hospital, Nanjing University School of Medicine and The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; West China Hospital, Chengdu, China; Renji Hospital, Ruijin Hospital, and Huashan Hospital, Shanghai, China; The First Affiliated Hospital of Zhejiang University, Hangzhou, China; The First Affiliated Hospital of Dalian Medical University, Dalian, China;
The Second Xiangya Hospital of Central South University, Changsha, China; Shenzhen Second People's Hospital, Shenzhen, China; Daping Hospital, Chongqing, China; The Second Affiliated Hospital of Jilin University, Changchun, China; The Third Hospital of Hebei Medical University, Hebei, China; and Guangdong General Hospital, Guangdong, China.
Nan Chen, MD
From Jinling Hospital, Nanjing University School of Medicine and The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; West China Hospital, Chengdu, China; Renji Hospital, Ruijin Hospital, and Huashan Hospital, Shanghai, China; The First Affiliated Hospital of Zhejiang University, Hangzhou, China; The First Affiliated Hospital of Dalian Medical University, Dalian, China;
The Second Xiangya Hospital of Central South University, Changsha, China; Shenzhen Second People's Hospital, Shenzhen, China; Daping Hospital, Chongqing, China; The Second Affiliated Hospital of Jilin University, Changchun, China; The Third Hospital of Hebei Medical University, Hebei, China; and Guangdong General Hospital, Guangdong, China.
Ying Li, MD
From Jinling Hospital, Nanjing University School of Medicine and The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; West China Hospital, Chengdu, China; Renji Hospital, Ruijin Hospital, and Huashan Hospital, Shanghai, China; The First Affiliated Hospital of Zhejiang University, Hangzhou, China; The First Affiliated Hospital of Dalian Medical University, Dalian, China;
The Second Xiangya Hospital of Central South University, Changsha, China; Shenzhen Second People's Hospital, Shenzhen, China; Daping Hospital, Chongqing, China; The Second Affiliated Hospital of Jilin University, Changchun, China; The Third Hospital of Hebei Medical University, Hebei, China; and Guangdong General Hospital, Guangdong, China.
Yong Gu, MD
From Jinling Hospital, Nanjing University School of Medicine and The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; West China Hospital, Chengdu, China; Renji Hospital, Ruijin Hospital, and Huashan Hospital, Shanghai, China; The First Affiliated Hospital of Zhejiang University, Hangzhou, China; The First Affiliated Hospital of Dalian Medical University, Dalian, China;
The Second Xiangya Hospital of Central South University, Changsha, China; Shenzhen Second People's Hospital, Shenzhen, China; Daping Hospital, Chongqing, China; The Second Affiliated Hospital of Jilin University, Changchun, China; The Third Hospital of Hebei Medical University, Hebei, China; and Guangdong General Hospital, Guangdong, China.
Wei Shi, MD
From Jinling Hospital, Nanjing University School of Medicine and The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; West China Hospital, Chengdu, China; Renji Hospital, Ruijin Hospital, and Huashan Hospital, Shanghai, China; The First Affiliated Hospital of Zhejiang University, Hangzhou, China; The First Affiliated Hospital of Dalian Medical University, Dalian, China;
The Second Xiangya Hospital of Central South University, Changsha, China; Shenzhen Second People's Hospital, Shenzhen, China; Daping Hospital, Chongqing, China; The Second Affiliated Hospital of Jilin University, Changchun, China; The Third Hospital of Hebei Medical University, Hebei, China; and Guangdong General Hospital, Guangdong, China.
Weixin Hu, MD
From Jinling Hospital, Nanjing University School of Medicine and The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; West China Hospital, Chengdu, China; Renji Hospital, Ruijin Hospital, and Huashan Hospital, Shanghai, China; The First Affiliated Hospital of Zhejiang University, Hangzhou, China; The First Affiliated Hospital of Dalian Medical University, Dalian, China;
The Second Xiangya Hospital of Central South University, Changsha, China; Shenzhen Second People's Hospital, Shenzhen, China; Daping Hospital, Chongqing, China; The Second Affiliated Hospital of Jilin University, Changchun, China; The Third Hospital of Hebei Medical University, Hebei, China; and Guangdong General Hospital, Guangdong, China.
Zhengzhao Liu, MD
From Jinling Hospital, Nanjing University School of Medicine and The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; West China Hospital, Chengdu, China; Renji Hospital, Ruijin Hospital, and Huashan Hospital, Shanghai, China; The First Affiliated Hospital of Zhejiang University, Hangzhou, China; The First Affiliated Hospital of Dalian Medical University, Dalian, China;
The Second Xiangya Hospital of Central South University, Changsha, China; Shenzhen Second People's Hospital, Shenzhen, China; Daping Hospital, Chongqing, China; The Second Affiliated Hospital of Jilin University, Changchun, China; The Third Hospital of Hebei Medical University, Hebei, China; and Guangdong General Hospital, Guangdong, China.
Hao Bao, MD
From Jinling Hospital, Nanjing University School of Medicine and The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; West China Hospital, Chengdu, China; Renji Hospital, Ruijin Hospital, and Huashan Hospital, Shanghai, China; The First Affiliated Hospital of Zhejiang University, Hangzhou, China; The First Affiliated Hospital of Dalian Medical University, Dalian, China;
The Second Xiangya Hospital of Central South University, Changsha, China; Shenzhen Second People's Hospital, Shenzhen, China; Daping Hospital, Chongqing, China; The Second Affiliated Hospital of Jilin University, Changchun, China; The Third Hospital of Hebei Medical University, Hebei, China; and Guangdong General Hospital, Guangdong, China.
Caihong Zeng, PhD
From Jinling Hospital, Nanjing University School of Medicine and The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; West China Hospital, Chengdu, China; Renji Hospital, Ruijin Hospital, and Huashan Hospital, Shanghai, China; The First Affiliated Hospital of Zhejiang University, Hangzhou, China; The First Affiliated Hospital of Dalian Medical University, Dalian, China;
The Second Xiangya Hospital of Central South University, Changsha, China; Shenzhen Second People's Hospital, Shenzhen, China; Daping Hospital, Chongqing, China; The Second Affiliated Hospital of Jilin University, Changchun, China; The Third Hospital of Hebei Medical University, Hebei, China; and Guangdong General Hospital, Guangdong, China.
Minlin Zhou, MD
From Jinling Hospital, Nanjing University School of Medicine and The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; West China Hospital, Chengdu, China; Renji Hospital, Ruijin Hospital, and Huashan Hospital, Shanghai, China; The First Affiliated Hospital of Zhejiang University, Hangzhou, China; The First Affiliated Hospital of Dalian Medical University, Dalian, China;
The Second Xiangya Hospital of Central South University, Changsha, China; Shenzhen Second People's Hospital, Shenzhen, China; Daping Hospital, Chongqing, China; The Second Affiliated Hospital of Jilin University, Changchun, China; The Third Hospital of Hebei Medical University, Hebei, China; and Guangdong General Hospital, Guangdong, China.
Grant Support: By the National Basic Research Program of China (973 Program, No. 2012CB517600, No. 2012CB517606), National Key Technology R&D Program (2011BA I10B04, 2013BAI09B04).
Reproducible Research Statement: Study protocol: Available at www.annals.org. Statistical code: Available from Dr. Zhang at [email protected]. Data set: not available.
Corresponding Author: Zhihong Liu, MD, National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing 210016, China; e-mail, [email protected].
Current Author Addresses: Drs. Zhihong Liu, Zhang, Hu, Zhengzhao Liu, Bao, Zeng, and Zhou: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, China, 210016.
Dr. Zhangsuo Liu: The First Affiliated Hospital, Zhengzhou University, No. 1 Jianshe Road, Zhengzhou, Henan, China, 450052.
Dr. Xing: The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, China, 210029.
Dr. Fu: West China Hospital, 37 Guoxue Xiang, Wuhou District, Chengdu, China, 610041.
Dr. Ni: Renji Hospital, Shanghai Jiaotong University School of Medicine, 160 Pujian Road, Shanghai, China, 200127.
Dr. Jianghua Chen: The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang, China, 310003.
Dr. Lin: The First Affiliated Hospital of Dalian Medical University, NO 222, Zhongshan Road, Dalian, China, 116011.
Dr. Fuyou Liu: The Second Xiangya Hospital, Central South University, No. 139 Renmin Middle Road, Changsha, Hunan, China, 410011.
Dr. Yongcheng He: Shenzhen Second People's Hospital, 3002 West Sungang Road, Futian District, Shenzhen, China, 518035.
Dr. Yani He: Daping Hospital, Third Military Medical University, 10 Changjiangzhilu Daping, Yuzhong District, Chongqing, China, 400042.
Dr. Miao: The Second Hospital of Jilin University, Ziqiang Street 218, Changchun, China, 130041.
Dr. Nan Chen: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 RuiJin Er Lu, Shanghai, China, 200025.
Dr. Li: The Third Hospital of Hebei Medical University, 102 Youyi North Street, Shijiazhuang, Hebei Province, China, 050081.
Dr. Gu: Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040.
Dr. Shi: Guangdong General Hospital, Guangdong Academy of Medical Science, 106 Zhongshan Er Road, Guangzhou, China, 510080.
Author Contributions: Conception and design: Zhihong Liu, H. Zhang, Zhangsuo Liu. P. Fu.
Analysis and interpretation of the data: Zhihong Liu, H. Zhang, Zhangsuo Liu, P. Fu, Zhengzhao Liu, H. Bao, C. Zeng.
Drafting of the article: Zhihong Liu, H. Zhang, P. Fu, H. Bao, C. Zeng.
Critical revision of the article for important intellectual content: Zhihong Liu, H. Zhang, Zhangsuo Liu, P. Fu, Zhengzhao Liu, H. Bao, C. Zeng, M. Zhou.
Final approval of the article: Zhihong Liu, H. Zhang, Zhangsuo Liu, C. Xing, P. Fu, Z. Ni, J. Chen, H. Lin, F. Liu, Yani He, L. Miao, N. Chen, Y. Gu, W. Shi, W. Hu, H. Bao, C. Zeng, M. Zhou.
Provision of study materials or patients: Zhihong Liu, H. Zhang, C. Xing, P. Fu, Z. Ni, J. Chen, H. Lin, F. Liu, Yongcheng He, Yani He, L. Miao, N. Chen, Y. Li, Y. Gu, W. Shi, W. Hu, Zhengzhao Liu, C. Zeng.
Statistical expertise: P. Fu, M. Zhou.
Obtaining of funding: Zhihong Liu, H. Zhang, P. Fu.
Administrative, technical, or logistic support: Zhihong Liu, H. Zhang, Zhengzhao Liu.
Collection and assembly of data: Zhihong Liu, H. Zhang, Zhangsuo Liu, C. Xing, P. Fu, J. Chen, H. Lin, F. Liu, Yongcheng He, N. Chen, W. Hu, Zhengzhao Liu, C. Zeng.
This article was published online first at www.annals.org on 11 November 2014.

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Zhihong Liu, Haitao Zhang, Zhangsuo Liu, et al. Multitarget Therapy for Induction Treatment of Lupus Nephritis: A Randomized Trial. Ann Intern Med.2015;162:18-26. [Epub 6 January 2015]. doi:10.7326/M14-1030

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