Skip to main content
Top
Published in: BMC Nephrology 1/2016

Open Access 01-12-2016 | Research article

Outcome of low dose cyclophosphamide for induction phase treatment of lupus nephritis, a single center study

Authors: Mahesh R. Sigdel, Mukunda P. Kafle, Dibya Singh Shah

Published in: BMC Nephrology | Issue 1/2016

Login to get access

Abstract

Background

The current standard for induction phase treatment of lupus nephritis is steroid combined with mycophenolate mofetil or pulse intravenous cyclophosphamide (IVC). The lowest dose of IVC recommended for induction therapy is that used in the Euro-Lupus Trial. It is not known whether same cumulative dose of IVC would be effective when given over six months.

Methods

We carried out a prospective, observational study on 41 patients of biopsy-proven lupus nephritis (class III, IV, V or mixed). For induction, patients received six pulses of monthly IVC (500 mg each), along with steroid. Patients were followed up monthly until one month beyond completion of the sixth pulse. The outcomes assessed were complete remission (proteinuria < 200 mg/day or urine albumin nil with serum albumin >35 gm/L, stable estimated glomerular filtration rate (eGFR) if normal at baseline or increase in eGFR by 25 % if abnormal at baseline and normal urinary sediment), response (complete or partial remissions), complications of therapy and death.

Results

Twenty two patients (53.7 %) had class IV nephritis. Eighteen patients (43.9 %) achieved complete remission, 16 (39.0 %) achieved partial remission, yielding an overall response rate of 82.9 %. Nephrotic range proteinuria (UTP ≥ 3 g/day) and severe hypoalbuminemia (serum albumin < 20 g/L) at baseline influenced remission (p <0.05). Infection, seen in 12 patients (29.3 %), was the most common complication. Four deaths (9.6 %) were observed, all due to infection.

Conclusions

For induction phase treatment, Nepalese patients with lupus nephritis responded favorably to steroid and low dose IVC of 3 grams given as six monthly pulses.
Literature
1.
go back to reference Bomback AS, Appel GB. Updates on the treatment of lupus nephritis. J Am Soc Nephrol. 2010;21:2028–35.CrossRefPubMed Bomback AS, Appel GB. Updates on the treatment of lupus nephritis. J Am Soc Nephrol. 2010;21:2028–35.CrossRefPubMed
2.
go back to reference Hahn BH, McMahon MA, Wilkinson A, et al. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res. 2012;64:797–808.CrossRef Hahn BH, McMahon MA, Wilkinson A, et al. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res. 2012;64:797–808.CrossRef
3.
go back to reference Appel GB, Contreras G, Dooley MA, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol. 2009;20:1103–12.CrossRefPubMedPubMedCentral Appel GB, Contreras G, Dooley MA, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol. 2009;20:1103–12.CrossRefPubMedPubMedCentral
4.
go back to reference Bertsias GK, Tektonidou M, Amoura Z, et al. 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;71:1771–82.CrossRefPubMedPubMedCentral Bertsias GK, Tektonidou M, Amoura Z, et al. 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;71:1771–82.CrossRefPubMedPubMedCentral
5.
go back to reference Bhat P, Radhakrishnan J. B lymphocytes and lupus nephritis: new insights into pathogenesis and targeted therapies. Kidney Int. 2008;73:261–8.CrossRefPubMed Bhat P, Radhakrishnan J. B lymphocytes and lupus nephritis: new insights into pathogenesis and targeted therapies. Kidney Int. 2008;73:261–8.CrossRefPubMed
6.
go back to reference Weening JJ, D’Agati VD, Schwartz MM, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int. 2004;65:521–30.CrossRefPubMed Weening JJ, D’Agati VD, Schwartz MM, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int. 2004;65:521–30.CrossRefPubMed
7.
go back to reference Kidney Disease. Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int Suppl. 2012;2:139–274. Kidney Disease. Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int Suppl. 2012;2:139–274.
8.
go back to reference Masood S, Jayne D, Karim Y. Beyond immunosuppression - challenges in the clinical management of lupus nephritis. Lupus. 2009;18:106–15.CrossRefPubMed Masood S, Jayne D, Karim Y. Beyond immunosuppression - challenges in the clinical management of lupus nephritis. Lupus. 2009;18:106–15.CrossRefPubMed
9.
go back to reference Ponticelli C, Glassock RJ, Moroni G. Induction and maintenance therapy in proliferative lupus nephritis. J Nephrol. 2010;23:9–16.PubMed Ponticelli C, Glassock RJ, Moroni G. Induction and maintenance therapy in proliferative lupus nephritis. J Nephrol. 2010;23:9–16.PubMed
10.
go back to reference Felson DT, Anderson J. Evidence for the superiority of immunosuppressive drugs and prednisone over prednisone alone in lupus nephritis. Results of a pooled analysis. N Engl J Med. 1984;311:1528–33.CrossRefPubMed Felson DT, Anderson J. Evidence for the superiority of immunosuppressive drugs and prednisone over prednisone alone in lupus nephritis. Results of a pooled analysis. N Engl J Med. 1984;311:1528–33.CrossRefPubMed
11.
go back to reference Austin 3rd HA, Klippel JH, Balow JE, et al. Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs. N Engl J Med. 1986;314:614–9.CrossRefPubMed Austin 3rd HA, Klippel JH, Balow JE, et al. Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs. N Engl J Med. 1986;314:614–9.CrossRefPubMed
12.
go back to reference Gourley MF, Austin 3rd HA, Scott D, et al. Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. Ann Intern Med. 1996;125:549–57.CrossRefPubMed Gourley MF, Austin 3rd HA, Scott D, et al. Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. Ann Intern Med. 1996;125:549–57.CrossRefPubMed
13.
go back to reference Houssiau FA, Vasconcelos C, D’Cruz D, et al. Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum. 2002;46:2121–31.CrossRefPubMed Houssiau FA, Vasconcelos C, D’Cruz D, et al. Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum. 2002;46:2121–31.CrossRefPubMed
14.
go back to reference Contreras G, Pardo V, Leclercq B, et al. Sequential therapies for proliferative lupus nephritis. N Engl J Med. 2004;350:971–80.CrossRefPubMed Contreras G, Pardo V, Leclercq B, et al. Sequential therapies for proliferative lupus nephritis. N Engl J Med. 2004;350:971–80.CrossRefPubMed
15.
go back to reference Houssiau FA, Vasconcelos C, D’Cruz D, et al. The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide. Ann Rheum Dis. 2010;69:61–4.CrossRefPubMed Houssiau FA, Vasconcelos C, D’Cruz D, et al. The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide. Ann Rheum Dis. 2010;69:61–4.CrossRefPubMed
16.
go back to reference Walsh M, James M, Jayne D, et al. Mycophenolate mofetil for induction therapy of lupus nephritis: a systematic review and meta-analysis. Clin J Am Soc Nephrol. 2007;2:968–75.CrossRefPubMed Walsh M, James M, Jayne D, et al. Mycophenolate mofetil for induction therapy of lupus nephritis: a systematic review and meta-analysis. Clin J Am Soc Nephrol. 2007;2:968–75.CrossRefPubMed
17.
go back to reference Chan TM, Li FK, Tang CS, et al. Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou Nephrology Study Group. N Engl J Med. 2000;343:1156–62.CrossRefPubMed Chan TM, Li FK, Tang CS, et al. Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou Nephrology Study Group. N Engl J Med. 2000;343:1156–62.CrossRefPubMed
18.
go back to reference Hu W, Liu Z, Chen H, et al. Mycophenolate mofetil vs cyclophosphamide therapy for patients with diffuse proliferative lupus nephritis. Chin Med J (Engl). 2002;115:705–9. Hu W, Liu Z, Chen H, et al. Mycophenolate mofetil vs cyclophosphamide therapy for patients with diffuse proliferative lupus nephritis. Chin Med J (Engl). 2002;115:705–9.
19.
go back to reference Ginzler EM, Dooley MA, Aranow C, et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med. 2005;353:2219–28.CrossRefPubMed Ginzler EM, Dooley MA, Aranow C, et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med. 2005;353:2219–28.CrossRefPubMed
20.
go back to reference Chan TM, Tse KC, Tang CS, et al. Long-term study of mycophenolate mofetil as continuous induction and maintenance treatment for diffuse proliferative lupus nephritis. J Am Soc Nephrol. 2005;16:1076–84.CrossRefPubMed Chan TM, Tse KC, Tang CS, et al. Long-term study of mycophenolate mofetil as continuous induction and maintenance treatment for diffuse proliferative lupus nephritis. J Am Soc Nephrol. 2005;16:1076–84.CrossRefPubMed
21.
go back to reference Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40:1725.CrossRefPubMed Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40:1725.CrossRefPubMed
22.
23.
go back to reference Tylicki L, Larczynski W, Rutkowski B. Renal protective effects of the renin-angiotensin-aldosterone system blockade: from evidence-based approach to perspectives. Kidney Blood Press Res. 2005;28:230–42.CrossRefPubMed Tylicki L, Larczynski W, Rutkowski B. Renal protective effects of the renin-angiotensin-aldosterone system blockade: from evidence-based approach to perspectives. Kidney Blood Press Res. 2005;28:230–42.CrossRefPubMed
24.
go back to reference Duran-Barragan S, McGwin Jr G, Vila LM, et al. Angiotensin-converting enzyme inhibitors delay the occurrence of renal involvement and are associated with a decreased risk of disease activity in patients with systemic lupus erythematosus--results from LUMINA (LIX): a multiethnic US cohort. Rheumatology (Oxford). 2008;47:1093–6.CrossRef Duran-Barragan S, McGwin Jr G, Vila LM, et al. Angiotensin-converting enzyme inhibitors delay the occurrence of renal involvement and are associated with a decreased risk of disease activity in patients with systemic lupus erythematosus--results from LUMINA (LIX): a multiethnic US cohort. Rheumatology (Oxford). 2008;47:1093–6.CrossRef
25.
go back to reference Ayodele OE, Okpechi IG, Swanepoel CR. Predictors of poor renal outcome in patients with biopsy-proven lupus nephritis. Nephrology. 2010;15:482–90.CrossRefPubMed Ayodele OE, Okpechi IG, Swanepoel CR. Predictors of poor renal outcome in patients with biopsy-proven lupus nephritis. Nephrology. 2010;15:482–90.CrossRefPubMed
26.
go back to reference Chen W, Tang X, Liu Q, et 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.CrossRefPubMed Chen W, Tang X, Liu Q, et 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.CrossRefPubMed
27.
go back to reference van Vollenhoven RF, Mosca M, Bertsias G, et al. Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. Ann Rheum Dis. 2014;73:958–67.CrossRefPubMed van Vollenhoven RF, Mosca M, Bertsias G, et al. Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. Ann Rheum Dis. 2014;73:958–67.CrossRefPubMed
28.
go back to reference Bagavant H, Kalantarinia K, Scindia Y, et al. Novel therapeutic approaches to lupus glomerulonephritis: translating animal models to clinical practice. Am J Kidney Dis. 2011;57:498–507.CrossRefPubMedPubMedCentral Bagavant H, Kalantarinia K, Scindia Y, et al. Novel therapeutic approaches to lupus glomerulonephritis: translating animal models to clinical practice. Am J Kidney Dis. 2011;57:498–507.CrossRefPubMedPubMedCentral
29.
go back to reference Demircin G. An Update on Treatment and Outcome of Lupus Nephritis in Children. Ann Paediatr Rheum. 2013;2:99–106.CrossRef Demircin G. An Update on Treatment and Outcome of Lupus Nephritis in Children. Ann Paediatr Rheum. 2013;2:99–106.CrossRef
30.
go back to reference Paudyal BP, Gyawalee M. Clinical profile of patients with systemic lupus erythematosus. JNMA J Nepal Med Assoc. 2012;52:111–7.PubMed Paudyal BP, Gyawalee M. Clinical profile of patients with systemic lupus erythematosus. JNMA J Nepal Med Assoc. 2012;52:111–7.PubMed
31.
go back to reference Yu F, Tan Y, Liu G, et al. Clinicopathological characteristics and outcomes of patients with crescentic lupus nephritis. Kidney Int. 2009;76:307–17.CrossRefPubMed Yu F, Tan Y, Liu G, et al. Clinicopathological characteristics and outcomes of patients with crescentic lupus nephritis. Kidney Int. 2009;76:307–17.CrossRefPubMed
32.
go back to reference Bertsias GK, Salmon JE, Boumpas DT. Therapeutic opportunities in systemic lupus erythematosus: state of the art and prospects for the new decade. Ann Rheum Dis. 2010;69:1603–11.CrossRefPubMed Bertsias GK, Salmon JE, Boumpas DT. Therapeutic opportunities in systemic lupus erythematosus: state of the art and prospects for the new decade. Ann Rheum Dis. 2010;69:1603–11.CrossRefPubMed
33.
go back to reference Cervera R, Khamashta MA, Font J, et al. Systemic lupus erythematosus: clinical and immunologic patterns of disease expression in a cohort of 1,000 patients. The European Working Party on Systemic Lupus Erythematosus. Medicine (Baltimore). 1993;72:113–24.CrossRef Cervera R, Khamashta MA, Font J, et al. Systemic lupus erythematosus: clinical and immunologic patterns of disease expression in a cohort of 1,000 patients. The European Working Party on Systemic Lupus Erythematosus. Medicine (Baltimore). 1993;72:113–24.CrossRef
34.
go back to reference Korbet SM, Lewis EJ. Complete remission in severe lupus nephritis: assessing the rate of loss in proteinuria. Nephrol Dial Transplant. 2012;27:2813–9.CrossRefPubMed Korbet SM, Lewis EJ. Complete remission in severe lupus nephritis: assessing the rate of loss in proteinuria. Nephrol Dial Transplant. 2012;27:2813–9.CrossRefPubMed
35.
go back to reference Houssiau FA, D’Cruz D, Sangle S, et al. Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial. Ann Rheum Dis. 2010;69:2083–9.CrossRefPubMedPubMedCentral Houssiau FA, D’Cruz D, Sangle S, et al. Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial. Ann Rheum Dis. 2010;69:2083–9.CrossRefPubMedPubMedCentral
36.
go back to reference Dooley MA, Jayne D, Ginzler EM, et al. Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N Engl J Med. 2011;365:1886–95.CrossRefPubMed Dooley MA, Jayne D, Ginzler EM, et al. Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N Engl J Med. 2011;365:1886–95.CrossRefPubMed
37.
go back to reference Yang XW, Tan Y, Yu F, et al. Combination of anti-C1q and anti-dsDNA antibodies is associated with higher renal disease activity and predicts renal prognosis of patients with lupus nephritis. Nephrol Dial Transplant. 2012;27:3552–9.CrossRefPubMed Yang XW, Tan Y, Yu F, et al. Combination of anti-C1q and anti-dsDNA antibodies is associated with higher renal disease activity and predicts renal prognosis of patients with lupus nephritis. Nephrol Dial Transplant. 2012;27:3552–9.CrossRefPubMed
38.
go back to reference Korbet SM, Schwartz MM, Evans J, et al. Severe lupus nephritis: racial differences in presentation and outcome. J Am Soc Nephrol. 2007;18:244–54.CrossRefPubMed Korbet SM, Schwartz MM, Evans J, et al. Severe lupus nephritis: racial differences in presentation and outcome. J Am Soc Nephrol. 2007;18:244–54.CrossRefPubMed
39.
go back to reference Austin 3rd HA, Boumpas DT, Vaughan EM, et al. Predicting renal outcomes in severe lupus nephritis: contributions of clinical and histologic data. Kidney Int. 1994;45:544–50.CrossRefPubMed Austin 3rd HA, Boumpas DT, Vaughan EM, et al. Predicting renal outcomes in severe lupus nephritis: contributions of clinical and histologic data. Kidney Int. 1994;45:544–50.CrossRefPubMed
40.
go back to reference Schwartz MM. The Holy Grail: pathological indices in lupus nephritis. Kidney Int. 2000;58:1354–5.CrossRefPubMed Schwartz MM. The Holy Grail: pathological indices in lupus nephritis. Kidney Int. 2000;58:1354–5.CrossRefPubMed
Metadata
Title
Outcome of low dose cyclophosphamide for induction phase treatment of lupus nephritis, a single center study
Authors
Mahesh R. Sigdel
Mukunda P. Kafle
Dibya Singh Shah
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2016
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-016-0361-0

Other articles of this Issue 1/2016

BMC Nephrology 1/2016 Go to the issue