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Published in: BMC Nephrology 1/2018

Open Access 01-12-2018 | Research article

Retrospective analysis of tacrolimus combined with Tripterygium wilfordii polyglycoside for treating idiopathic membranous nephropathy

Authors: Shun-Lai Shang, Guang-Yan Cai, Shu-wei Duan, Ping Li, Qing-Gang Li, Xiang-Mei Chen

Published in: BMC Nephrology | Issue 1/2018

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Abstract

Background

Idiopathic membranous nephropathy (IMN) is one of the most common adult nephrotic syndromes. Some patients with this disorder require immunosuppressive therapy. This retrospective case series was performed to assess the effects of tacrolimus (TAC) combined with Tripterygium wilfordii polyglycoside (TWG) in treating IMN.

Methods

From January 2015 to August 2016, kidney-biopsy-proven IMN patients treated with TAC in the Chinese PLA General Hospital were screened. Data were retrieved from the patients’ medical records. The first efficacy evaluation index was remission rate (complete remission and partial remission), and the secondary efficacy evaluation indices included relapse rate, proteinuria, serum albumin and estimated glomerular filtration rate (eGFR). Adverse events were also assessed.

Results

The included patients’ treatments were tacrolimus monotherapy (TAC group, n = 33), tacrolimus combined with methylprednisolone (MP) (TAC + MP group, n = 24) and tacrolimus combined with Tripterygium wilfordii polyglycoside (TAC + TWG group, n = 21). The remission rates of the TAC, TAC + MP, and TAC + TWG groups in the 10th month were 54.5, 62.5, and 85.7%, respectively (TAC + TWG group vs TAC group, P = 0.037, TAC + TWG group vs TAC + MP group, P = 0.125). Moreover, the complete remission rates of the TAC, TAC + MP, and TAC + TWG groups in the 10th month were 21.2, 20.8, and 57.1%, respectively (TAC + TWG group vs TAC group, P = 0.007, TAC + TWG group vs TAC + MP group, P = 0.012). Compared with the TAC group, the TAC + TWG group had a higher remission rate during these ten months (log-rank, P = 0.005). Compared with the TAC and TAC + MP groups, the TAC + TWG group had a higher complete remission rate (log-rank, P = 0.019 and log-rank, P = 0.005, respectively).

Conclusion

This retrospective study showed that TAC combined with TWG may be effective for treating IMN. Further randomized controlled trials (RCTs) are needed to assess the efficacy and safety of TAC combined with TWG.
Literature
1.
go back to reference du Buf-Vereijken PW, Branten AJ, Wetzels JF. Idiopathic membranous nephropathy:outline and rationale of a treatment strategy [J]. Am J Kidney Dis. 2005;46(6):1012–29.CrossRefPubMed du Buf-Vereijken PW, Branten AJ, Wetzels JF. Idiopathic membranous nephropathy:outline and rationale of a treatment strategy [J]. Am J Kidney Dis. 2005;46(6):1012–29.CrossRefPubMed
2.
go back to reference Hofstra JM, Wetzels JF. Management of patients with membranous nephropathy [J]. Nephrol Dial Transplant. 2012;27(1):6–9.CrossRefPubMed Hofstra JM, Wetzels JF. Management of patients with membranous nephropathy [J]. Nephrol Dial Transplant. 2012;27(1):6–9.CrossRefPubMed
3.
go back to reference Hofstra JM, Wetzels JF. Alkylating agents in membranous nephropathy: efficacy proven beyond doubt [J]. Nephrol Dial Transplant. 2010;25(6):1760–6.CrossRefPubMed Hofstra JM, Wetzels JF. Alkylating agents in membranous nephropathy: efficacy proven beyond doubt [J]. Nephrol Dial Transplant. 2010;25(6):1760–6.CrossRefPubMed
4.
go back to reference Radhakrishnan J, Cattran DC. The KDIGO practice guideline on glomerulonephritis: reading between the (guide) lines-application to the individual patient. Kidney Int. 2012;82(8):840–56.CrossRefPubMed Radhakrishnan J, Cattran DC. The KDIGO practice guideline on glomerulonephritis: reading between the (guide) lines-application to the individual patient. Kidney Int. 2012;82(8):840–56.CrossRefPubMed
5.
go back to reference Jha V, Ganguli A, Saha TK, Kohli HS, Sud K, et al. A randomized, controlled trial of steroids and cyclophosphamide in adults with nephrotic syndrome caused by idiopathic membranous nephropathy. J Am SocNePhrol. 2007;18(6):1899–904. Jha V, Ganguli A, Saha TK, Kohli HS, Sud K, et al. A randomized, controlled trial of steroids and cyclophosphamide in adults with nephrotic syndrome caused by idiopathic membranous nephropathy. J Am SocNePhrol. 2007;18(6):1899–904.
6.
go back to reference Praga M, Barrio V, Juarez GF, NefroPatia M. Tacrolimus monotherapy in membranous nephropathy: a randomized controlled trial. Kidney Int. 2007;71(9):924–30.CrossRefPubMed Praga M, Barrio V, Juarez GF, NefroPatia M. Tacrolimus monotherapy in membranous nephropathy: a randomized controlled trial. Kidney Int. 2007;71(9):924–30.CrossRefPubMed
7.
go back to reference Segarra A, Vila J, Pou L, et al. Combined therapy of tacrolimus and corticosteroids in cyclosporin-resistant or –dependent idiopathic focal glomerulosclerosis: a preliminary uncontrolled study with prospective follow-up. Nephrol Dial Transplant. 2002;17(4):655.CrossRefPubMed Segarra A, Vila J, Pou L, et al. Combined therapy of tacrolimus and corticosteroids in cyclosporin-resistant or –dependent idiopathic focal glomerulosclerosis: a preliminary uncontrolled study with prospective follow-up. Nephrol Dial Transplant. 2002;17(4):655.CrossRefPubMed
8.
go back to reference Ramachandran R, Hn HK, Kumar V, Nada R, Yadav AK, Goyal A, et al. Tacrolimus combined with corticosteroids versus Modified ponticelli regimen in treatment of idiopathic membranous nephropathy: randomized control trial. Nephrology (Carlton). 2016;21(2):139–46. https://doi.org/10.1111/nep.12569.CrossRef Ramachandran R, Hn HK, Kumar V, Nada R, Yadav AK, Goyal A, et al. Tacrolimus combined with corticosteroids versus Modified ponticelli regimen in treatment of idiopathic membranous nephropathy: randomized control trial. Nephrology (Carlton). 2016;21(2):139–46. https://​doi.​org/​10.​1111/​nep.​12569.CrossRef
9.
go back to reference Zhen QS, Ye X, Wei ZJ. Recent progress in research on Tripterygium: a male antifertility plant. Contraception. 1995;51(2):121–9.CrossRefPubMed Zhen QS, Ye X, Wei ZJ. Recent progress in research on Tripterygium: a male antifertility plant. Contraception. 1995;51(2):121–9.CrossRefPubMed
10.
go back to reference Wan Y, Gu L, Suzuki K, Karasawa T, et al. Multi-glycoside of tripterygium wilfordii hook f. Ameliorates proteinuria and acute mesangial injury induced by anti-Thy1.1 monoclonal antibody. Nephron Exp Nephrol. 2005;99(4):e121–9.CrossRefPubMed Wan Y, Gu L, Suzuki K, Karasawa T, et al. Multi-glycoside of tripterygium wilfordii hook f. Ameliorates proteinuria and acute mesangial injury induced by anti-Thy1.1 monoclonal antibody. Nephron Exp Nephrol. 2005;99(4):e121–9.CrossRefPubMed
11.
go back to reference Chen BJ. Triptolide, a novel immunosuppressive and anti-inflammatory agent purified from a Chinese herb tripterygium wilfordii hook F. Leuk LymPhoma. 2001;42(3):253–65.CrossRefPubMed Chen BJ. Triptolide, a novel immunosuppressive and anti-inflammatory agent purified from a Chinese herb tripterygium wilfordii hook F. Leuk LymPhoma. 2001;42(3):253–65.CrossRefPubMed
12.
go back to reference Geng Y, Fang M, Wang J, Yu H, Hu Z, Yew DT, Chen W. Triptolide down-regulates COX-2 expression and PGE2 release by suppressing the activity of NF-κB and MAP kinases in lipopolysaccharide-treated PC12 cells. Phytother Res PTR. 2012;26:337–43.PubMed Geng Y, Fang M, Wang J, Yu H, Hu Z, Yew DT, Chen W. Triptolide down-regulates COX-2 expression and PGE2 release by suppressing the activity of NF-κB and MAP kinases in lipopolysaccharide-treated PC12 cells. Phytother Res PTR. 2012;26:337–43.PubMed
13.
go back to reference Premkumar V, Dey M, Dorn R, Raskin I. MyD88-dependent and independent pathways of toll-like receptors are engaged in biological activity of triptolide in ligand-stimulated macrophages. BMC Chem Biol. 2010;10(1):3.CrossRefPubMedPubMedCentral Premkumar V, Dey M, Dorn R, Raskin I. MyD88-dependent and independent pathways of toll-like receptors are engaged in biological activity of triptolide in ligand-stimulated macrophages. BMC Chem Biol. 2010;10(1):3.CrossRefPubMedPubMedCentral
15.
go back to reference He WZ, Yin ZH, Gao JH, Ye ZZ, Xie Y, Kong WH, et al. Etanercept combinedwith Tripterygium wilfordii polyglycoside for treatment of rheumatoid arthritis in the elderly: a clinical study. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2014;34(3):267–71.PubMed He WZ, Yin ZH, Gao JH, Ye ZZ, Xie Y, Kong WH, et al. Etanercept combinedwith Tripterygium wilfordii polyglycoside for treatment of rheumatoid arthritis in the elderly: a clinical study. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2014;34(3):267–71.PubMed
16.
go back to reference Liu G, Shen Y, You L, Song W, Lu K, Li Y. Tripterygium wilfordii polyglycoside suppresses inflammatory cytokine expression in rats with diabetic nephropathy. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2014;30(7):721–4.PubMed Liu G, Shen Y, You L, Song W, Lu K, Li Y. Tripterygium wilfordii polyglycoside suppresses inflammatory cytokine expression in rats with diabetic nephropathy. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2014;30(7):721–4.PubMed
17.
go back to reference Liu S, Li X, Li H, Liang Q, Chen J. Comparison of tripterygium wilfordii multiglycosides and tacrolimus in the treatment of idiopathic membranous nephropathy: a prospective cohort study. BMC Nephrol. 2015;16:200.CrossRefPubMedPubMedCentral Liu S, Li X, Li H, Liang Q, Chen J. Comparison of tripterygium wilfordii multiglycosides and tacrolimus in the treatment of idiopathic membranous nephropathy: a prospective cohort study. BMC Nephrol. 2015;16:200.CrossRefPubMedPubMedCentral
18.
go back to reference Troyanov S, Roasio L, Pandes M, et al. Renal pathology in idiopathic membranous nephropathy: a new perspective. Kidney Int. 2006;69(9):1641–8.CrossRefPubMed Troyanov S, Roasio L, Pandes M, et al. Renal pathology in idiopathic membranous nephropathy: a new perspective. Kidney Int. 2006;69(9):1641–8.CrossRefPubMed
20.
go back to reference Glassock RJ. The pathogenesis of idiopathic membranous nephropathy: a 50-year odyssey. Am J Kidney Dis. 2010;56(1):157–67.CrossRefPubMed Glassock RJ. The pathogenesis of idiopathic membranous nephropathy: a 50-year odyssey. Am J Kidney Dis. 2010;56(1):157–67.CrossRefPubMed
21.
go back to reference Petermann A, SJ CWGS, et al. Mechanical stress reduces podocyte proliferation in vitro. Kidney Int. 2002;61:40–50.CrossRefPubMed Petermann A, SJ CWGS, et al. Mechanical stress reduces podocyte proliferation in vitro. Kidney Int. 2002;61:40–50.CrossRefPubMed
22.
go back to reference Pippin JW, Durvasula R, Petermann A, Hiromura K, Couser WG. Shankland SJ. DNA damage is a novel response to sublytic complement C5b-9-induced injury in podocytes. J Clin Invest. 2003;111(6):877–85.CrossRefPubMedPubMedCentral Pippin JW, Durvasula R, Petermann A, Hiromura K, Couser WG. Shankland SJ. DNA damage is a novel response to sublytic complement C5b-9-induced injury in podocytes. J Clin Invest. 2003;111(6):877–85.CrossRefPubMedPubMedCentral
24.
go back to reference Winn MP.2007 Yong Investigator Award. TRPing into a new era for glomerular disease [J]. J Am Soc Nephrol. 2008;19(6):1071–5.CrossRef Winn MP.2007 Yong Investigator Award. TRPing into a new era for glomerular disease [J]. J Am Soc Nephrol. 2008;19(6):1071–5.CrossRef
25.
go back to reference Nonaka K, Ubara Y, Suwabe T, et al. Intractable membranous lupus nephritis showing selective improvement of subepithelial deposits with tacrolimus therapy: a case report [J]. Clin Nephrol. 2013;80(2):140–5.CrossRefPubMed Nonaka K, Ubara Y, Suwabe T, et al. Intractable membranous lupus nephritis showing selective improvement of subepithelial deposits with tacrolimus therapy: a case report [J]. Clin Nephrol. 2013;80(2):140–5.CrossRefPubMed
26.
go back to reference Textor SC, Burnett JC Jr, Romero JC, et al. Urinary endothelin and renal vasoconstriction with cyclosporine or FK506 after liver transplantation [J]. Kidney Int. 1995;47:1426–33.CrossRefPubMed Textor SC, Burnett JC Jr, Romero JC, et al. Urinary endothelin and renal vasoconstriction with cyclosporine or FK506 after liver transplantation [J]. Kidney Int. 1995;47:1426–33.CrossRefPubMed
27.
go back to reference Chen Z-H, Qin W-S, Zeng C-H. Triptolide reduces proteinuria in experimental membranous nephropathy and protects against C5b-9-induced podocyte injury in vitro. Kidney International. 2010;77:974–88.CrossRefPubMed Chen Z-H, Qin W-S, Zeng C-H. Triptolide reduces proteinuria in experimental membranous nephropathy and protects against C5b-9-induced podocyte injury in vitro. Kidney International. 2010;77:974–88.CrossRefPubMed
30.
go back to reference Qiu D, Zhao G, Aoki Y, Shi L, Uyei A, Nazarian S, Ng JC, Kao PN. Immunosuppressant PG490 (triptolide) inhibits T-cell interleukin-2 expression at the level of purine-box/nuclear factor of activated T-cells and NF-kappaB transcriptional activation. J Biol Chem. 1999;274(19):13443–50.CrossRefPubMed Qiu D, Zhao G, Aoki Y, Shi L, Uyei A, Nazarian S, Ng JC, Kao PN. Immunosuppressant PG490 (triptolide) inhibits T-cell interleukin-2 expression at the level of purine-box/nuclear factor of activated T-cells and NF-kappaB transcriptional activation. J Biol Chem. 1999;274(19):13443–50.CrossRefPubMed
31.
go back to reference Yang Y, Liu Z, Tolosa E. Triptolide induces apoptotie death of T lymphocyte. Immunopharmaeology. 1998;40:139–49.CrossRef Yang Y, Liu Z, Tolosa E. Triptolide induces apoptotie death of T lymphocyte. Immunopharmaeology. 1998;40:139–49.CrossRef
32.
go back to reference Abboud OI, Adler S, Agarwal R, Andreoli SP, Becker GJ, Brown F, et al. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int. 2012;2(Suppl 2):186–97. Abboud OI, Adler S, Agarwal R, Andreoli SP, Becker GJ, Brown F, et al. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int. 2012;2(Suppl 2):186–97.
33.
go back to reference Chen M, Li H, Li XY, et al. Tacrolimus combined with corticosteroids in treatment of nephrotic idiopathic membranous nephropathy: a multicenter randomized controlled trial. Am J Med Sci. 2010;339:233–8.CrossRefPubMed Chen M, Li H, Li XY, et al. Tacrolimus combined with corticosteroids in treatment of nephrotic idiopathic membranous nephropathy: a multicenter randomized controlled trial. Am J Med Sci. 2010;339:233–8.CrossRefPubMed
34.
go back to reference Beck LH Jr, Bonegio RG, Lambeau G, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med. 2009;361:11.CrossRefPubMedPubMedCentral Beck LH Jr, Bonegio RG, Lambeau G, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med. 2009;361:11.CrossRefPubMedPubMedCentral
36.
go back to reference Hoxha E, Harendza S, Pinnschmidt HO, Tomas NM, Helmchen U, Panzer U, et al. Spontaneous remission of proteinuria is a frequent event in phospholipase A2 receptor antibody-negative patients with membranous nephropathy. Nephrol Dial Transplant. 2015;30(11):1862–9. https://doi.org/10.1093/ndt/gfv228. Epub 2015 Jul 3CrossRefPubMed Hoxha E, Harendza S, Pinnschmidt HO, Tomas NM, Helmchen U, Panzer U, et al. Spontaneous remission of proteinuria is a frequent event in phospholipase A2 receptor antibody-negative patients with membranous nephropathy. Nephrol Dial Transplant. 2015;30(11):1862–9. https://​doi.​org/​10.​1093/​ndt/​gfv228. Epub 2015 Jul 3CrossRefPubMed
37.
go back to reference Kidney Disease. Improving Global Outcomes (KDIGO) CKD Work Group. Clinical practice guideline for the evaluation and management of Chronic Kidney Disease. Kidney Int Suppl. 2013;3:1–150.CrossRef Kidney Disease. Improving Global Outcomes (KDIGO) CKD Work Group. Clinical practice guideline for the evaluation and management of Chronic Kidney Disease. Kidney Int Suppl. 2013;3:1–150.CrossRef
39.
go back to reference Tao X, Lipsky PE. The Chinese anti-inflammatory and immunosuppressive herbal remedy tripterygium wilfordii Hook F. Rheum Dis Clin North Am. 2000;26(1):29–50.CrossRefPubMed Tao X, Lipsky PE. The Chinese anti-inflammatory and immunosuppressive herbal remedy tripterygium wilfordii Hook F. Rheum Dis Clin North Am. 2000;26(1):29–50.CrossRefPubMed
40.
go back to reference Chen JR, Yen JH, Lin CC, et al. The effects of Chinese herbs on improving survival and inhibiting anti-ds DNA antibodyproduction in lupus mice. Am J Chinese Med. 1993;21(3–4):257–62.CrossRef Chen JR, Yen JH, Lin CC, et al. The effects of Chinese herbs on improving survival and inhibiting anti-ds DNA antibodyproduction in lupus mice. Am J Chinese Med. 1993;21(3–4):257–62.CrossRef
41.
go back to reference Abboud OI, Adler S, Agarwal R, Andreoli SP, Becker GJ, Brown F, et al. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int. 2012;2(Suppl 2):156–62. Abboud OI, Adler S, Agarwal R, Andreoli SP, Becker GJ, Brown F, et al. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int. 2012;2(Suppl 2):156–62.
Metadata
Title
Retrospective analysis of tacrolimus combined with Tripterygium wilfordii polyglycoside for treating idiopathic membranous nephropathy
Authors
Shun-Lai Shang
Guang-Yan Cai
Shu-wei Duan
Ping Li
Qing-Gang Li
Xiang-Mei Chen
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2018
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-018-0967-5

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