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Published in: International Urology and Nephrology 11/2019

01-11-2019 | Leflunomide | Nephrology - Review

Efficacy and safety of leflunomide in IgA nephropathy: a systematic review and meta-analysis

Authors: Jianwei Yi, Zhihong He, Shizhang Xu, Si Feng

Published in: International Urology and Nephrology | Issue 11/2019

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Abstract

Background

The optimal therapy for immunoglobulin A nephropathy (IgAN) remains uncertain. Leflunomide (LEF) is an immunosuppressive drug which may reduce deposition of glomerular autoantibodies and immune complexes. Several clinical trials were designed to evaluate the efficacy of LEF, but their results were controversial.

Methods

Ovid Medline, Embase, the Cochrane Library, PubMed, and CNKI were systematically searched. Search terms included (“glomerulonephritis” OR “nephritis”) AND (“immunoglobulin A” OR “IgA”) AND “leflunomide”. Studies in which patients were diagnosed with IgAN based on renal biopsy were included. Studies needed to report clinical outcomes via either short- or long-term clinical examination, remission rate, or complication rate.

Results

Forty-four studies encompassing 1802 patients were included, of which 35 were randomized controlled trials. Results of 24 h post-treatment urine protein tests and serum creatinine tests were significantly lower in patients treat with LEF and corticosteroids (CS) or valsartan (ACEI) (CS + LEF or CS + ACEI) compared with patients treated with CS or ACEI alone (P < 0.05). More patients treated with CS + LEF (31.2%) achieved complete remission (CR) than patients treated with CS alone (22.2%) (RR = 0.71, 95% CI 0.59–0.85, P < 0.05). Although there was no significant difference in CR between patients treated with cyclophosphamide and CS (CS + CTX) and those treated with CS + LEF, the complication rate in the former group was higher (28.4%) than in the latter one (11.4%) (RR = 2.46, 95% CI 1.47–4.13, P < 0.005).

Conclusion

LEF appears to improve renal function while decreasing loss of urine protein. Combination regimens including LEF were better and safer compared with CS or ACEI alone or combinations including CTX.
Appendix
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Literature
1.
go back to reference Conley M, Cooper M, Michael A (1980) Selective deposition of immunoglobulin A1 in immunoglobulin A nephropathy, anaphylactoid purpura nephritis, and systemic lupus erythematosus. J Clin Investig 66(6):1432–1436CrossRefPubMedPubMedCentral Conley M, Cooper M, Michael A (1980) Selective deposition of immunoglobulin A1 in immunoglobulin A nephropathy, anaphylactoid purpura nephritis, and systemic lupus erythematosus. J Clin Investig 66(6):1432–1436CrossRefPubMedPubMedCentral
2.
go back to reference McGrogan A, Franssen CF, de Vries CS (2010) The incidence of primary glomerulonephritis worldwide: a systematic review of the literature. Oxford University Press, Oxford McGrogan A, Franssen CF, de Vries CS (2010) The incidence of primary glomerulonephritis worldwide: a systematic review of the literature. Oxford University Press, Oxford
3.
go back to reference Koyama A, Igarashi M, Kobayashi M (1997) Natural history and risk factors for immunoglobulin A nephropathy in Japan. Am J Kidney Dis 29(4):526–532CrossRefPubMed Koyama A, Igarashi M, Kobayashi M (1997) Natural history and risk factors for immunoglobulin A nephropathy in Japan. Am J Kidney Dis 29(4):526–532CrossRefPubMed
4.
go back to reference Zimmerman SW, Burkholder PM (1975) Immunoglobulin A nephropathy. Arch Intern Med 135(9):1217–1223CrossRefPubMed Zimmerman SW, Burkholder PM (1975) Immunoglobulin A nephropathy. Arch Intern Med 135(9):1217–1223CrossRefPubMed
5.
go back to reference Li PKT, Ho KKL, Szeto CC, Yu L, Lai FMM (2002) Prognostic indicators of IgA nephropathy in the Chinese—clinical and pathological perspectives. Nephrol Dial Transplant 17(1):64–69CrossRefPubMed Li PKT, Ho KKL, Szeto CC, Yu L, Lai FMM (2002) Prognostic indicators of IgA nephropathy in the Chinese—clinical and pathological perspectives. Nephrol Dial Transplant 17(1):64–69CrossRefPubMed
6.
go back to reference Szeto C-C, Lai FM-M, To K-F, Wong TY-H, Chow K-M, Choi PC-L, Lui S-F, Li PK-T (2001) The natural history of immunoglobulin a nephropathy among patients with hematuria and minimal proteinuria. Am J Med 110(6):434–437CrossRefPubMed Szeto C-C, Lai FM-M, To K-F, Wong TY-H, Chow K-M, Choi PC-L, Lui S-F, Li PK-T (2001) The natural history of immunoglobulin a nephropathy among patients with hematuria and minimal proteinuria. Am J Med 110(6):434–437CrossRefPubMed
7.
go back to reference Emancipator SN, Lamm ME (1990) IgA nephropathy: pathogenesis of the most common form of glomerulonephritis. Humana Press, Totowa, NJ, pp 113–128 Emancipator SN, Lamm ME (1990) IgA nephropathy: pathogenesis of the most common form of glomerulonephritis. Humana Press, Totowa, NJ, pp 113–128
9.
go back to reference Boyd JK, Cheung CK, Molyneux K, Feehally J, Barratt J (2012) An update on the pathogenesis and treatment of IgA nephropathy. Kidney Int 81(9):833–843CrossRefPubMed Boyd JK, Cheung CK, Molyneux K, Feehally J, Barratt J (2012) An update on the pathogenesis and treatment of IgA nephropathy. Kidney Int 81(9):833–843CrossRefPubMed
11.
go back to reference Zhang Z, Yang Y, Jiang S-M, Li W-G (2019) Efficacy and safety of immunosuppressive treatment in IgA nephropathy: a meta-analysis of randomized controlled trials. arXiv:515023 Zhang Z, Yang Y, Jiang S-M, Li W-G (2019) Efficacy and safety of immunosuppressive treatment in IgA nephropathy: a meta-analysis of randomized controlled trials. arXiv:​515023
12.
go back to reference Zhang C, Chu M (2018) Leflunomide: a promising drug with good antitumor potential. Biochem Biophys Res Commun 496(2):726–730CrossRefPubMed Zhang C, Chu M (2018) Leflunomide: a promising drug with good antitumor potential. Biochem Biophys Res Commun 496(2):726–730CrossRefPubMed
13.
go back to reference Jiang X, Mo Y, Sun L, Yue Z, Chen S, Wu W (2009) Efficacy of methylprednisolone, cyclophosphamide in pediatric IgA nephropathy assessed by renal biopsy. Clin Nephrol 71(6):625–631CrossRefPubMed Jiang X, Mo Y, Sun L, Yue Z, Chen S, Wu W (2009) Efficacy of methylprednisolone, cyclophosphamide in pediatric IgA nephropathy assessed by renal biopsy. Clin Nephrol 71(6):625–631CrossRefPubMed
14.
go back to reference Tam L, Li E, Wong C, Lam CW, Szeto C (2004) Double-blind, randomized, placebo-controlled pilot study of leflunomide in systemic lupus erythematosus. Lupus 13(8):601–604CrossRefPubMed Tam L, Li E, Wong C, Lam CW, Szeto C (2004) Double-blind, randomized, placebo-controlled pilot study of leflunomide in systemic lupus erythematosus. Lupus 13(8):601–604CrossRefPubMed
16.
go back to reference Lou T, Wang C, Chen Z, Shi C, Tang H, Liu X, Yin P, Yu X (2006) Randomised controlled trial of leflunomide in the treatment of immunoglobulin A nephropathy. Nephrology 11(2):113–116CrossRefPubMed Lou T, Wang C, Chen Z, Shi C, Tang H, Liu X, Yin P, Yu X (2006) Randomised controlled trial of leflunomide in the treatment of immunoglobulin A nephropathy. Nephrology 11(2):113–116CrossRefPubMed
17.
go back to reference Cheng G, Liu D, Margetts P, Liu L, Zhao Z, Liu Z, Tang L, Fang Y, Li H, Guo Y (2015) Valsartan combined with clopidogrel and/or leflunomide for the treatment of progressive immunoglobulin A nephropathy. Nephrology 20(2):77–84CrossRefPubMed Cheng G, Liu D, Margetts P, Liu L, Zhao Z, Liu Z, Tang L, Fang Y, Li H, Guo Y (2015) Valsartan combined with clopidogrel and/or leflunomide for the treatment of progressive immunoglobulin A nephropathy. Nephrology 20(2):77–84CrossRefPubMed
18.
go back to reference Min L, Wang Q, Cao L, Zhou W, Yuan J, Zhang M, Che X, Mou S, Fang W, Gu L, Zhu M, Wang L, Yu Z, Qian J, Ni Z (2017) Comparison of combined leflunomide and low-dose corticosteroid therapy with full-dose corticosteroid monotherapy for progressive IgA nephropathy. Oncotarget 8(29):48375–48384CrossRefPubMedPubMedCentral Min L, Wang Q, Cao L, Zhou W, Yuan J, Zhang M, Che X, Mou S, Fang W, Gu L, Zhu M, Wang L, Yu Z, Qian J, Ni Z (2017) Comparison of combined leflunomide and low-dose corticosteroid therapy with full-dose corticosteroid monotherapy for progressive IgA nephropathy. Oncotarget 8(29):48375–48384CrossRefPubMedPubMedCentral
19.
go back to reference Mao F (2018) Effect of leflunomide combined with prednisone on renal function in patients with progressive IgA nephropathy. Zhong Guo Liao Yang Yi Xue 27(05):535–536 Mao F (2018) Effect of leflunomide combined with prednisone on renal function in patients with progressive IgA nephropathy. Zhong Guo Liao Yang Yi Xue 27(05):535–536
20.
go back to reference Bian F (2019) Efficacy and safety of leflunomide in the treatment of patients with IgA nephropathy. Ji Cen Yi Xue Lun Tan 23(04):504–505 Bian F (2019) Efficacy and safety of leflunomide in the treatment of patients with IgA nephropathy. Ji Cen Yi Xue Lun Tan 23(04):504–505
21.
go back to reference Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097CrossRefPubMedPubMedCentral Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097CrossRefPubMedPubMedCentral
22.
go back to reference Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, Savović J, Schulz KF, Weeks L, Sterne JA (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928CrossRefPubMedPubMedCentral Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, Savović J, Schulz KF, Weeks L, Sterne JA (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928CrossRefPubMedPubMedCentral
23.
go back to reference Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25(9):603–605CrossRefPubMed Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25(9):603–605CrossRefPubMed
24.
go back to reference Guo M (2012) Comparison of steroid combined with leflunomide or cyclophosphamide in the treatment of chronic progressive IgA nephropathy. Zhong Guo Yi Yao Za Zhi 10(28):142–143 Guo M (2012) Comparison of steroid combined with leflunomide or cyclophosphamide in the treatment of chronic progressive IgA nephropathy. Zhong Guo Yi Yao Za Zhi 10(28):142–143
25.
go back to reference Luo N (2015) Clinical study of steroid combined with leflunomide or cyclophosphamide in the treatment of chronic progressive IgA nephropathy. Master Degree Thesis, Da Lian Yi Ke Da Xue Luo N (2015) Clinical study of steroid combined with leflunomide or cyclophosphamide in the treatment of chronic progressive IgA nephropathy. Master Degree Thesis, Da Lian Yi Ke Da Xue
26.
go back to reference Shen J, Li D, Zhu X, Yang J, Tang J (2010) A prospective controlled study of leflunomide and ACEI in the treatment of IgAN. Zhong Hua Quan Ke Yi Xue 8(10):1217–1219 Shen J, Li D, Zhu X, Yang J, Tang J (2010) A prospective controlled study of leflunomide and ACEI in the treatment of IgAN. Zhong Hua Quan Ke Yi Xue 8(10):1217–1219
27.
go back to reference Hu Y, Ke G, Xiang Y, Huang X, Peng X (2018) Effect of leflunomide on serum vascular endothelial growth factor and endothelin levels in patients with IgA nephropathy. Chong Qing Yi Xue 47(09):1191–1193 Hu Y, Ke G, Xiang Y, Huang X, Peng X (2018) Effect of leflunomide on serum vascular endothelial growth factor and endothelin levels in patients with IgA nephropathy. Chong Qing Yi Xue 47(09):1191–1193
28.
go back to reference Su X, Bao B, You X, Li G, Liu T (2013) A comparative study of leflunomide and cyclophosphamide in the treatment of IgA nephropathy (Haas type III ~ IV). Xian Dai Shi Yong Yi Xue 25(08):851–853 Su X, Bao B, You X, Li G, Liu T (2013) A comparative study of leflunomide and cyclophosphamide in the treatment of IgA nephropathy (Haas type III ~ IV). Xian Dai Shi Yong Yi Xue 25(08):851–853
29.
go back to reference Zhong Z, Chen G (2011) A comparative study of leflunomide and cyclophosphamide in the treatment of IgA nephropathy with nephrotic syndrome. Hua Bei Mei Tan Yi Xue Yuan Xue Bao 13(05):593–594 Zhong Z, Chen G (2011) A comparative study of leflunomide and cyclophosphamide in the treatment of IgA nephropathy with nephrotic syndrome. Hua Bei Mei Tan Yi Xue Yuan Xue Bao 13(05):593–594
30.
go back to reference Feng H (2012) Therapeutic effect of leflunomide combined with hormone on IgA nephropathy. Dang Dai Yi Xue 18(30):139–140 Feng H (2012) Therapeutic effect of leflunomide combined with hormone on IgA nephropathy. Dang Dai Yi Xue 18(30):139–140
31.
go back to reference Tao J (2016) Clinical observation of leflunomide combined with hormone in the treatment of IgA nephropathy. Ji Cen Yi Xue Lun Tan 20(36):5109–5110 Tao J (2016) Clinical observation of leflunomide combined with hormone in the treatment of IgA nephropathy. Ji Cen Yi Xue Lun Tan 20(36):5109–5110
32.
go back to reference Yang D, Luo C, Jiang W, Tao Z (2010) Therapeutic effect of leflunomide combined with steroid on patients with IgA nephropathy. Zhong Guo Dang Dai Yi Yao 17(13):74–75 Yang D, Luo C, Jiang W, Tao Z (2010) Therapeutic effect of leflunomide combined with steroid on patients with IgA nephropathy. Zhong Guo Dang Dai Yi Yao 17(13):74–75
33.
go back to reference Zhang C, Liu L, Zhu X (2014) Clinical analysis of leflunomide combined with hormone therapy in patients with IgA nephropathy. Zhong Guo She Qu Yi Shi 30(31):40–41 Zhang C, Liu L, Zhu X (2014) Clinical analysis of leflunomide combined with hormone therapy in patients with IgA nephropathy. Zhong Guo She Qu Yi Shi 30(31):40–41
34.
go back to reference Zhao X, Liu B, Zhang W, Zhang L, Li G (2017) Clinical efficacy of leflunomide combined with hormone therapy for IgA nephropathy with tubulointerstitial damage. Ying Xiang Yan Jiu Yu Yi Xue Ying Yong 1(11):224–226 Zhao X, Liu B, Zhang W, Zhang L, Li G (2017) Clinical efficacy of leflunomide combined with hormone therapy for IgA nephropathy with tubulointerstitial damage. Ying Xiang Yan Jiu Yu Yi Xue Ying Yong 1(11):224–226
35.
go back to reference Zhang L (2010) Therapeutic effect of leflunomide combined with hormone on chronic progressive IgA nephropathy. Zhong Guo Xian Dai Yao Wu Guan Li 4(20):116–118 Zhang L (2010) Therapeutic effect of leflunomide combined with hormone on chronic progressive IgA nephropathy. Zhong Guo Xian Dai Yao Wu Guan Li 4(20):116–118
36.
go back to reference Xu C, Jiao H (2018) Clinical observation of leflunomide combined with steroid in the treatment of refractory IgA nephropathy. Shi Jie Zui Xin Yi Xue Xin Xi Wen Zhai 18(74):106 Xu C, Jiao H (2018) Clinical observation of leflunomide combined with steroid in the treatment of refractory IgA nephropathy. Shi Jie Zui Xin Yi Xue Xin Xi Wen Zhai 18(74):106
37.
go back to reference Chen L (2016) Clinical observation of leflunomide combined with hormone in the treatment of refractory IgA nephropathy. Dang Dai Yi Xue 22(23):118–119 Chen L (2016) Clinical observation of leflunomide combined with hormone in the treatment of refractory IgA nephropathy. Dang Dai Yi Xue 22(23):118–119
38.
go back to reference Lin Y, Wang F, Sun M (2009) Clinical efficacy of leflunomide combined with steroid therapy in young women with IgA nephropathy. Zhong Guo Fu You Bao Jian 24(34):4929–4930 Lin Y, Wang F, Sun M (2009) Clinical efficacy of leflunomide combined with steroid therapy in young women with IgA nephropathy. Zhong Guo Fu You Bao Jian 24(34):4929–4930
39.
go back to reference Zhang J, Zhang C, Geng Y, Ding T (2012) A comparative study of leflunomide combined with kesuiya and simple application of kesuiya in the treatment of IgA nephropathy. Wu Jing Yi Xue 23(07):599–600, 604 Zhang J, Zhang C, Geng Y, Ding T (2012) A comparative study of leflunomide combined with kesuiya and simple application of kesuiya in the treatment of IgA nephropathy. Wu Jing Yi Xue 23(07):599–600, 604
40.
go back to reference Sui J (2011) Clinical study of leflunomide combined with tripterygium glycosides in the treatment of IgA nephropathy. Zhong Guo Yi Yao Dao Bao 8(11):67–68 Sui J (2011) Clinical study of leflunomide combined with tripterygium glycosides in the treatment of IgA nephropathy. Zhong Guo Yi Yao Dao Bao 8(11):67–68
41.
go back to reference Cui Y, Wu S (2018) Effect of leflunomide combined with prednisone in the treatment of IgA nephropathy. Dang Dai Yi Xue 16(15):121–122 Cui Y, Wu S (2018) Effect of leflunomide combined with prednisone in the treatment of IgA nephropathy. Dang Dai Yi Xue 16(15):121–122
42.
go back to reference Liu D (2017) Therapeutic effect of leflunomide combined with prednisone on patients with refractory primary IgA nephropathy. Dang Dai Yi Xue 23(34):114–115 Liu D (2017) Therapeutic effect of leflunomide combined with prednisone on patients with refractory primary IgA nephropathy. Dang Dai Yi Xue 23(34):114–115
43.
go back to reference He X, Zhu Z, Ke T, Huang T, Chen W (2013) Therapeutic effect of leflunomide combined with prednisone on patients with refractory primary IgA nephropathy. Zhong Guo Yi Yao Dao Bao 10(12):81–83 He X, Zhu Z, Ke T, Huang T, Chen W (2013) Therapeutic effect of leflunomide combined with prednisone on patients with refractory primary IgA nephropathy. Zhong Guo Yi Yao Dao Bao 10(12):81–83
44.
go back to reference Zeng L, Yin C, Huang L (2015) Effect of leflunomide combined with glucocorticoid on the efficacy of patients with IgA nephropathy. Zhong Guo Dang Dai Yi Sheng 53(34):21–24 Zeng L, Yin C, Huang L (2015) Effect of leflunomide combined with glucocorticoid on the efficacy of patients with IgA nephropathy. Zhong Guo Dang Dai Yi Sheng 53(34):21–24
45.
go back to reference Zhang H, Zhang Y, Chen W (2013) Therapeutic effect of leflunomide combined with glucocorticoid versus cyclophosphamide combined with glucocorticoid on IgA nephropathy. Tai Shan Yi Xue Yuan Xue Bao 34(06):434–436 Zhang H, Zhang Y, Chen W (2013) Therapeutic effect of leflunomide combined with glucocorticoid versus cyclophosphamide combined with glucocorticoid on IgA nephropathy. Tai Shan Yi Xue Yuan Xue Bao 34(06):434–436
46.
go back to reference Hu C (2015) Therapeutic effect of leflunomide combined with glucocorticoid on IgA nephropathy. He Nan Yi Xue Yan Jiu 24(05):100 Hu C (2015) Therapeutic effect of leflunomide combined with glucocorticoid on IgA nephropathy. He Nan Yi Xue Yan Jiu 24(05):100
47.
go back to reference Wu S, Wang J (2014) Therapeutic effect of leflunomide combined with glucocorticoid on IgA nephropathy. Zhong Guo Shi Yong Zhen Duan Yu Zhi Liao Za Zhi 28(05):504–506 Wu S, Wang J (2014) Therapeutic effect of leflunomide combined with glucocorticoid on IgA nephropathy. Zhong Guo Shi Yong Zhen Duan Yu Zhi Liao Za Zhi 28(05):504–506
48.
go back to reference Yang Y, Chang X, Cheng M, Yang Y, Zhao M (2016) Efficacy of leflunomide combined with glucocorticoids in the treatment of progressive IgA nephropathy and its effect on VCAM-1 levels. Xian Dai Sheng Wu Yi Xue Jin Zhan 16(11):2134–2137 Yang Y, Chang X, Cheng M, Yang Y, Zhao M (2016) Efficacy of leflunomide combined with glucocorticoids in the treatment of progressive IgA nephropathy and its effect on VCAM-1 levels. Xian Dai Sheng Wu Yi Xue Jin Zhan 16(11):2134–2137
49.
go back to reference Shi C (2017) Efficacy of leflunomide combined with glucocorticoids in the treatment of progressive IgA nephropathy and its effect on VCAM-1 levels. Zhong Guo Dang Dai Yi Yao 24(31):80–82 Shi C (2017) Efficacy of leflunomide combined with glucocorticoids in the treatment of progressive IgA nephropathy and its effect on VCAM-1 levels. Zhong Guo Dang Dai Yi Yao 24(31):80–82
50.
go back to reference Li T, Feng A, Liu Y, Wu X, Huang Y, Chen Y (2011) Study of leflunomide combined with glucocorticoids in the treatment of progressive IgA nephropathy. Xian Dai Zhong Xi Yi Jie He Za Zhi 20(01):13–15 Li T, Feng A, Liu Y, Wu X, Huang Y, Chen Y (2011) Study of leflunomide combined with glucocorticoids in the treatment of progressive IgA nephropathy. Xian Dai Zhong Xi Yi Jie He Za Zhi 20(01):13–15
51.
go back to reference Zhao Q, Li W (2015) Clinical effect analysis of leflunomide combined with glucocorticoids in the treatment of IgA nephropathy. You Jiang Min Zu Yi Xue Yuan Xue Bao 37(02):222–225 Zhao Q, Li W (2015) Clinical effect analysis of leflunomide combined with glucocorticoids in the treatment of IgA nephropathy. You Jiang Min Zu Yi Xue Yuan Xue Bao 37(02):222–225
52.
go back to reference Shen P (2012) Therapeutic effect of leflunomide combined with low-dose steriod on IgA nephropathy. Zhong Hua Quan Ke Yi Xue 10(10):1580–1581 Shen P (2012) Therapeutic effect of leflunomide combined with low-dose steriod on IgA nephropathy. Zhong Hua Quan Ke Yi Xue 10(10):1580–1581
53.
go back to reference Dong J, Wang X, Wang J, Zou D (2017) Effect of leflunomide combined with low-dose prednisone on proliferative IgA nephropathy. Shan Dong Yi Yao 57(28):51–53 Dong J, Wang X, Wang J, Zou D (2017) Effect of leflunomide combined with low-dose prednisone on proliferative IgA nephropathy. Shan Dong Yi Yao 57(28):51–53
54.
go back to reference Zhao J, Ji Y (2018) Clinical efficacy of leflunomide combined with moderate dose of prednisone in the treatment of IgA nephropathy and its effect on serum ICAM-1 MCP-1 TGF-β_1. He Bei Yi Xue 24(06):914–918 Zhao J, Ji Y (2018) Clinical efficacy of leflunomide combined with moderate dose of prednisone in the treatment of IgA nephropathy and its effect on serum ICAM-1 MCP-1 TGF-β_1. He Bei Yi Xue 24(06):914–918
55.
go back to reference Feng L, Xu X, Liu Q, Liang W, Zhao J (2018) Clinical effect and safety analysis of leflunomide combined with moderate dose prednisone in the treatment of IgA nephropathy. Jie Fang Jun Yi Yao Za Zhi 30(09):97–100 Feng L, Xu X, Liu Q, Liang W, Zhao J (2018) Clinical effect and safety analysis of leflunomide combined with moderate dose prednisone in the treatment of IgA nephropathy. Jie Fang Jun Yi Yao Za Zhi 30(09):97–100
56.
go back to reference Cao L, Ni Z, Yan Y, Fang Y, Zhang W, Mu S, Wang Q, Zhang M, Qian J (2009) Study of leflunomide combined with low-dose glucocorticoids in the treatment of progressive IgA nephropathy. Shang Hai Yi Xue 32(09):791–795 Cao L, Ni Z, Yan Y, Fang Y, Zhang W, Mu S, Wang Q, Zhang M, Qian J (2009) Study of leflunomide combined with low-dose glucocorticoids in the treatment of progressive IgA nephropathy. Shang Hai Yi Xue 32(09):791–795
57.
go back to reference Sun Z, Wang L, Liu B, Wu X, Liu X, Zhang Z, Zhang Y, You Y, Shan W (2009) Comparative analysis of the efficacy of leflunomide and cyclophosphamide in the treatment of IgA nephropathy with renal dysfunction. Su Zhou Da Xue Xue Bao 29(05):961–963 Sun Z, Wang L, Liu B, Wu X, Liu X, Zhang Z, Zhang Y, You Y, Shan W (2009) Comparative analysis of the efficacy of leflunomide and cyclophosphamide in the treatment of IgA nephropathy with renal dysfunction. Su Zhou Da Xue Xue Bao 29(05):961–963
58.
go back to reference Chang J, Zhang W, Song X, Qiu X, Yuan D, Zheng Y (2011) A comparative study of leflunomide and tripterygium glycosides in the treatment of IgA nephropathy. Zhong Guo Shi Yong Yi Yao 6(25):9–10 Chang J, Zhang W, Song X, Qiu X, Yuan D, Zheng Y (2011) A comparative study of leflunomide and tripterygium glycosides in the treatment of IgA nephropathy. Zhong Guo Shi Yong Yi Yao 6(25):9–10
59.
go back to reference Shen S, Yang Z, Cai J, Xie Q, Hu Y, Sun L, Jiang Z (2016) Clinical efficacy and safety of leflunomide and prednisone in immunoglobulin A nephropathy. Zhong Guo Lin Chuang Yao Li 32(01):6–8 Shen S, Yang Z, Cai J, Xie Q, Hu Y, Sun L, Jiang Z (2016) Clinical efficacy and safety of leflunomide and prednisone in immunoglobulin A nephropathy. Zhong Guo Lin Chuang Yao Li 32(01):6–8
60.
go back to reference Xiang H (2017) Therapeutic effect of leflunomide combined with prednisone in the treatment of progressive IgA nephropathy. Beng Bu Yi Xue Yuan Xue Bao 42(12):1656–1658 Xiang H (2017) Therapeutic effect of leflunomide combined with prednisone in the treatment of progressive IgA nephropathy. Beng Bu Yi Xue Yuan Xue Bao 42(12):1656–1658
61.
go back to reference Wang X (2016) Efficacy and safety of leflunomide in the treatment of IgA nephropathy. Zhong Guo shi Yong Yi Yao 11(21):148–149 Wang X (2016) Efficacy and safety of leflunomide in the treatment of IgA nephropathy. Zhong Guo shi Yong Yi Yao 11(21):148–149
62.
go back to reference Shi X, Chen T (2017) Analysis of the effect of glucocorticoid combined with leflunomide in the treatment of IgA nephropathy. Lin Chuang Yi Xue Yan Jiu Yu Shi Jian 2(07):29–30 Shi X, Chen T (2017) Analysis of the effect of glucocorticoid combined with leflunomide in the treatment of IgA nephropathy. Lin Chuang Yi Xue Yan Jiu Yu Shi Jian 2(07):29–30
63.
go back to reference Cabral DBC, de Sandes-Freitas TV, Medina-Pestana JO, Mastroianni-Kirsztajn G (2018) Clinical features, treatment and prognostic factors of post-transplant immunoglobulin a nephropathy. Ann Transplant 23:166CrossRefPubMedCentral Cabral DBC, de Sandes-Freitas TV, Medina-Pestana JO, Mastroianni-Kirsztajn G (2018) Clinical features, treatment and prognostic factors of post-transplant immunoglobulin a nephropathy. Ann Transplant 23:166CrossRefPubMedCentral
64.
go back to reference Rauen T, Fitzner C, Eitner F, Sommerer C, Zeier M, Otte B, Panzer U, Peters H, Benck U, Mertens PR (2018) Effects of two immunosuppressive treatment protocols for IgA nephropathy. J Am Soc Nephrol 29(1):317–325CrossRefPubMed Rauen T, Fitzner C, Eitner F, Sommerer C, Zeier M, Otte B, Panzer U, Peters H, Benck U, Mertens PR (2018) Effects of two immunosuppressive treatment protocols for IgA nephropathy. J Am Soc Nephrol 29(1):317–325CrossRefPubMed
65.
go back to reference Rauen T, Eitner F, Fitzner C, Sommerer C, Zeier M, Otte B, Panzer U, Peters H, Benck U, Mertens PR (2015) Intensive supportive care plus immunosuppression in IgA nephropathy. N Engl J Med 373(23):2225–2236CrossRefPubMed Rauen T, Eitner F, Fitzner C, Sommerer C, Zeier M, Otte B, Panzer U, Peters H, Benck U, Mertens PR (2015) Intensive supportive care plus immunosuppression in IgA nephropathy. N Engl J Med 373(23):2225–2236CrossRefPubMed
66.
go back to reference Xie L, Tan C, Fan J, Fu P, Tang Y, Tao Y, Qin W (2013) Mycophenolic acid reverses IgA 1 aberrant glycosylation through up-regulating Cosmc expression in IgA nephropathy. Int Urol Nephrol 45(2):571–579CrossRefPubMed Xie L, Tan C, Fan J, Fu P, Tang Y, Tao Y, Qin W (2013) Mycophenolic acid reverses IgA 1 aberrant glycosylation through up-regulating Cosmc expression in IgA nephropathy. Int Urol Nephrol 45(2):571–579CrossRefPubMed
67.
go back to reference Xu G, Tu W, Jiang D, Xu C (2009) Mycophenolate mofetil treatment for IgA nephropathy: a meta-analysis. Am J Nephrol 29(5):362–367CrossRefPubMed Xu G, Tu W, Jiang D, Xu C (2009) Mycophenolate mofetil treatment for IgA nephropathy: a meta-analysis. Am J Nephrol 29(5):362–367CrossRefPubMed
68.
go back to reference Du B, Jia Y, Zhou W, Min X, Miao L, Cui W (2017) Efficacy and safety of mycophenolate mofetil in patients with IgA nephropathy: an update meta-analysis. BMC Nephrol 18(1):245CrossRefPubMedPubMedCentral Du B, Jia Y, Zhou W, Min X, Miao L, Cui W (2017) Efficacy and safety of mycophenolate mofetil in patients with IgA nephropathy: an update meta-analysis. BMC Nephrol 18(1):245CrossRefPubMedPubMedCentral
69.
go back to reference Yoshikawa N, Nakanishi K, Ishikura K, Hataya H, Iijima K, Honda M, Group JPINTS (2008) Combination therapy with mizoribine for severe childhood IgA nephropathy: a pilot study. Pediatric Nephrology 23(5):757–763CrossRefPubMed Yoshikawa N, Nakanishi K, Ishikura K, Hataya H, Iijima K, Honda M, Group JPINTS (2008) Combination therapy with mizoribine for severe childhood IgA nephropathy: a pilot study. Pediatric Nephrology 23(5):757–763CrossRefPubMed
70.
go back to reference Kim Y-C, Chin HJ, Koo HS, Kim S (2013) Tacrolimus decreases albuminuria in patients with IgA nephropathy and normal blood pressure: a double-blind randomized controlled trial of efficacy of tacrolimus on IgA nephropathy. PLoS One 8(8):e71545CrossRefPubMedPubMedCentral Kim Y-C, Chin HJ, Koo HS, Kim S (2013) Tacrolimus decreases albuminuria in patients with IgA nephropathy and normal blood pressure: a double-blind randomized controlled trial of efficacy of tacrolimus on IgA nephropathy. PLoS One 8(8):e71545CrossRefPubMedPubMedCentral
71.
go back to reference Zhang Q, Shi S-f, Zhu L, Lv J-C, Liu L-J, Chen Y-Q, Zhang H, Wang H-Y (2012) Tacrolimus improves the proteinuria remission in patients with refractory IgA nephropathy. Am J Nephrol 35(4):312–320CrossRefPubMed Zhang Q, Shi S-f, Zhu L, Lv J-C, Liu L-J, Chen Y-Q, Zhang H, Wang H-Y (2012) Tacrolimus improves the proteinuria remission in patients with refractory IgA nephropathy. Am J Nephrol 35(4):312–320CrossRefPubMed
72.
go back to reference Liu Y, Xiao J, Shi X, Hao G, Chen Q, Zhou J, Wei X (2016) Immunosuppressive agents versus steroids in the treatment of IgA nephropathy-induced proteinuria: a meta-analysis. Exp Therap Med 11(1):49–56CrossRef Liu Y, Xiao J, Shi X, Hao G, Chen Q, Zhou J, Wei X (2016) Immunosuppressive agents versus steroids in the treatment of IgA nephropathy-induced proteinuria: a meta-analysis. Exp Therap Med 11(1):49–56CrossRef
73.
go back to reference Liu X, Li D, Xu G, Sun S (2010) Comparison of the therapeutic effects of leflunomide and mycophenolate mofetil in the treatment of immunoglobulin A nephropathy manifesting with nephrotic syndrome. Int J Clin Pharmacol Ther 48(8):509–513CrossRefPubMed Liu X, Li D, Xu G, Sun S (2010) Comparison of the therapeutic effects of leflunomide and mycophenolate mofetil in the treatment of immunoglobulin A nephropathy manifesting with nephrotic syndrome. Int J Clin Pharmacol Ther 48(8):509–513CrossRefPubMed
74.
go back to reference Meng X-M, Chung AC, Lan HY (2013) Role of the TGF-β/BMP-7/Smad pathways in renal diseases. Clin Sci 124(4):243–254CrossRef Meng X-M, Chung AC, Lan HY (2013) Role of the TGF-β/BMP-7/Smad pathways in renal diseases. Clin Sci 124(4):243–254CrossRef
75.
go back to reference Bartlett R, Raiss R, Popovic S (1988) Development of auto immunity in MRL/Ipr mice and the effects of drugs on this murine disease. Scand J Rheumatol 17(sup75):290–299CrossRef Bartlett R, Raiss R, Popovic S (1988) Development of auto immunity in MRL/Ipr mice and the effects of drugs on this murine disease. Scand J Rheumatol 17(sup75):290–299CrossRef
76.
go back to reference Chen YZ, Zhao XZ, Wu J, Mei CL (2010) Combination regimen of leflunomide plus methylprednisolone in a female patient with reactive arthritis and concomitant IgA nephropathy. Chin Med J 123(3):375–378PubMed Chen YZ, Zhao XZ, Wu J, Mei CL (2010) Combination regimen of leflunomide plus methylprednisolone in a female patient with reactive arthritis and concomitant IgA nephropathy. Chin Med J 123(3):375–378PubMed
77.
go back to reference Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, Barasch J, Devarajan P (2003) Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol 14(10):2534–2543CrossRefPubMed Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, Barasch J, Devarajan P (2003) Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol 14(10):2534–2543CrossRefPubMed
78.
go back to reference Nangaku M (2004) Mechanisms of tubulointerstitial injury in the kidney: final common pathways to end-stage renal failure. Int Med 43(1):9–17CrossRef Nangaku M (2004) Mechanisms of tubulointerstitial injury in the kidney: final common pathways to end-stage renal failure. Int Med 43(1):9–17CrossRef
Metadata
Title
Efficacy and safety of leflunomide in IgA nephropathy: a systematic review and meta-analysis
Authors
Jianwei Yi
Zhihong He
Shizhang Xu
Si Feng
Publication date
01-11-2019
Publisher
Springer Netherlands
Keyword
Leflunomide
Published in
International Urology and Nephrology / Issue 11/2019
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-019-02255-6

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