Background: Mycophenolate (MF) is effective as a maintenance therapy after induction therapy in patients with lupus nephritis (LN). However, little is known about its role in patients with impaired renal function. The purpose of this study was to evaluate the efficacy and safety of MF as a maintenance therapy for LN and its association with renal function. Methods: Data were obtained for 56 Spanish patients who were receiving MF as a maintenance therapy for LN. Patients were classified into two groups according to renal function at the initiation of MF treatment: group 1 [estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2] and group 2 (eGFR <60 ml/min/1.73 m2). The primary endpoints of the study were the rates of renal relapse and responses, and their relationship with baseline renal function. Secondary outcomes were the appearance of side effects during treatment. Results: At initiation of MF treatment, the only differences between the groups were for age, hemoglobin levels, anti-DNA antibody titer, proteinuria, and renal function. In group 1 (n = 38), the eGFR was 98 ± 34 ml/min/1.73 m2 and in group 2 (n = 18) the eGFR was 43 ± 14 ml/min/1.73 m2. Only 3 cases had an eGFR <30 ml/min/1.73 m2. No significant differences were observed in the rate of relapse at 6 months (group 1: 20%; group 2: 23%) or at 12 months (group 1: 25%; group 2: 17%). Response rates were also similar in both groups. Side effects were unremarkable. Conclusions: MF is effective and safe as a maintenance therapy for LN both in patients with normal renal function and in those with renal impairment.

Keywords:
Lupus nephritis, Systemic lupus erythematous, Mycophenolate, Renal failure
1.
Bomback AS, Appel GB: Updates on the treatment of lupus nephritis. J Am Soc Nephrol 2010;21:2028-2035.
2.
Ponticelli C, Glassock RJ, Moroni G: Induction and maintenance therapy in proliferative lupus nephritis. J Nephrol 2010;23:9-16.
3.
Rivera F, Fulladosa X, Poveda R, Frutos MA, Garcia-Frias P, Ara J, Illescas L, Lopez-Rubio E, Merida E, Carreno A, Ballarin J, Fernandez-Juarez G, Baltar J, Ramos C, Pons S, Oliet A, Vigil A, Praga M, Segarra A: Mycophenolate as induction therapy in lupus nephritis with renal function impairment. Am J Nephrol 2012;35:424-433.
4.
Sprangers B, Monahan M, Appel GB: Diagnosis and treatment of lupus nephritis flares - an update. Nat Rev Nephrol 2012;8:709-717.
5.
Lenz O, Waheed AA, Baig A, Pop A, Contreras G: Lupus nephritis: maintenance therapy for lupus nephritis - do we now have a plan? Clin J Am Soc Nephrol 2013;8:162-171.
6.
Illei GG, Takada K, Parkin D, Austin HA, Crane M, Yarboro CH, Vaughan EM, Kuroiwa T, Danning CL, Pando J, Steinberg AD, Gourley MF, Klippel JH, Balow JE, Boumpas DT: Renal flares are common in patients with severe proliferative lupus nephritis treated with pulse immunosuppressive therapy: long-term followup of a cohort of 145 patients participating in randomized controlled studies. Arthritis Rheum 2002;46:995-1002.
7.
Flanc RS, Roberts MA, Strippoli GF, Chadban SJ, Kerr PG, Atkins RC: Treatment of diffuse proliferative lupus nephritis: a meta-analysis of randomized controlled trials. Am J Kidney Dis 2004;43:197-208.
8.
Houssiau FA, D'Cruz D, Sangle S, Remy P, Vasconcelos C, Petrovic R, Fiehn C, de Ramon Garrido E, Gilboe IM, Tektonidou M, Blockmans D, Ravelingien I, le Guern V, Depresseux G, Guillevin L, Cervera R: Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial. Ann Rheum Dis 2010;69:2083-2089.
9.
Dooley MA, Jayne D, Ginzler EM, Isenberg D, Olsen NJ, Wofsy D, Eitner F, Appel GB, Contreras G, Lisk L, Solomons N: Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N Eng J Med 2011;365:1886-1895.
10.
Patel SB, Korbet SM, Lewis EJ: The prognosis of severe lupus nephritis based on the modification of diet in renal disease (MDRD) study estimated glomerular filtration rate. Lupus 2011;20:256-264.
11.
Contreras G, Pardo V, Leclercq B, Lenz O, Tozman E, O'Nan P, Roth D: Sequential therapies for proliferative lupus nephritis. N Eng J Med 2004;350:971-980.
12.
Houssiau FA, Vasconcelos C, D'Cruz D, Sebastiani GD, Garrido Ed Ede R, Danieli MG, Abramovicz D, Blockmans D, Mathieu A, Direskeneli H, Galeazzi M, Gul A, Levy Y, Petera P, Popovic R, Petrovic R, Sinico RA, Cattaneo R, Font J, Depresseux G, Cosyns JP, Cervera R: Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum 2002;46:2121-2131.
13.
Chan TM, Tse KC, Tang CS, Mok MY, Li FK: Long-term study of mycophenolate mofetil as continuous induction and maintenance treatment for diffuse proliferative lupus nephritis. J Am Soc Nephrol 2005;16:1076-1084.
14.
Moroni G, Doria A, Mosca M, Alberighi ODC, Ferraccioli G, Todesco S, Manno C, Altieri P, Ferrara R, Greco S, Ponticelli C: A randomized pilot trial comparing cyclosporine and azathioprine for maintenance therapy in diffuse lupus nephritis over four years. Clin J Am Soc Nephrol 2006;1:925-932.
15.
Grootscholten C, Ligtenberg G, Hagen EC, van den Wall Bake AW, de Glas-Vos JW, Bijl M, Assmann KJ, Bruijn JA, Weening JJ, van Houwelingen HC, Derksen RH, Berden JH: Azathioprine/methylprednisolone versus cyclophosphamide in proliferative lupus nephritis. A randomized controlled trial. Kidney Int 2006;70:732-742.
16.
Austin HA 3rd, Illei GG, Braun MJ, Balow JE: Randomized, controlled trial of prednisone, cyclophosphamide, and cyclosporine in lupus membranous nephropathy. J Am Soc Nephrol 2009;20:901-911.
17.
Chen W, Liu Q, Chen W, Tang X, Fu P, Liu F, Liao Y, Yang Z, Zhang J, Chen J, Lou T, Fu J, Kong Y, Liu Z, Li Z, Yu X: Outcomes of maintenance therapy with tacrolimus versus azathioprine for active lupus nephritis: a multicenter randomized clinical trial. Lupus 2012;21:944-952.
18.
Sahin GM, Sahin S, Kiziltas S, Masatlioglu S, Oguz F, Ergin H: Mycophenolate mofetil versus azathioprine in the maintenance therapy of lupus nephritis. Ren Fail 2008;30:865-869.
19.
Elyan M, Ballou S: The effectiveness and safety of mycophenolate mofetil in lupus nephritis. Clin Rheumatol 2009;28:835-840.
20.
Rabrenovic V, Poskurica M, Kovacevic Z, Nesic V, Savin M, Mitic B, Dimkovic N, Cuckovic C, Vujic D, Pljesa S, Perunicic-Pekovic G, Curic S, Mitic I, Ratkovic M, Marinkovic J, Jovanovic D: Treatment of lupus nephritis by mycophenolate mofetil. Kidney Blood Press Res 2010;33:297-303.
21.
Appel GB, Contreras G, Dooley MA, Ginzler EM, Isenberg D, Jayne D, Li L-S, Mysler E, Sanchez-Guerrero J, Solomons N, Wofsy D, The Aspreva Lupus Management Study Group: Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol 2009;20:1103-1112.
22.
Zhu B, Chen N, Lin Y, Ren H, Zhang W, Wang W, Pan X, Yu H: Mycophenolate mofetil in induction and maintenance therapy of severe lupus nephritis: a meta-analysis of randomized controlled trials. Nephrol Dial Transplant 2007;22:1933-1942.
23.
Navaneethan SD, Viswanathan G, Strippoli GF: Treatment options for proliferative lupus nephritis: an update of clinical trial evidence. Drugs 2008;68:2095-2104.
24.
Mak A, Cheak AA, Tan JY, Su HC, Ho RC, Lau CS: Mycophenolate mofetil is as efficacious as, but safer than, cyclophosphamide in the treatment of proliferative lupus nephritis: a meta-analysis and meta-regression. Rheumatology (Oxford) 2009;48:944-952.
25.
Lee YH, Woo JH, Choi SJ, Ji JD, Song GG: Induction and maintenance therapy for lupus nephritis: a systematic review and meta-analysis. Lupus 2010;19:703-710.
26.
Henderson LK, Masson P, Craig JC, Roberts MA, Flanc RS, Strippoli GF, Webster AC: Induction and maintenance treatment of proliferative lupus nephritis: a meta-analysis of randomized controlled trials. Am J Kidney Dis 2013;61:74-87.
27.
Griffiths B, Emery P, Ryan V, Isenberg D, Akil M, Thompson R, Maddison P, Griffiths ID, Lorenzi A, Miles S, Situnayake D, Teh LS, Plant M, Hallengren C, Nived O, Sturfelt G, Chakravarty K, Tait T, Gordon C: The BILAG multi-centre open randomized controlled trial comparing ciclosporin vs azathioprine in patients with severe SLE. Rheumatology (Oxford) 2010;49:723-732.
28.
Houssiau F: Toward better treatment for lupus nephritis. N Engl J Med 2011;365:1929-1930.
29.
Stoenoiu MS, Aydin S, Tektonidou M, Ravelingien I, le Guern V, Fiehn C, Remy P, Delahousse M, Petera P, Quémeneur T, Vasconcelos C, D'Cruz D, Gilboe IM, Jadoul M, Karras A, Depresseux G, Guillevin L, Cervera R, Cosyns JP, Houssiau FA: Repeat kidney biopsies fail to detect differences between azathioprine and mycophenolate mofetil maintenance therapy for lupus nephritis: data from the MAINTAIN Nephritis Trial. Nephrol Dial Transplant 2012;27:1924-1930.
30.
Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group: KDIGO clinical practice guideline for glomerulonephritis. Chapter 12: lupus nephritis. Kidney Int 2012;2(suppl):221-&#x200B;232.
31.
Bertsias GK, Tektonidou M, Amoura Z, Aringer M, Bajema I, Berden JH, Boletis J, Cervera R, Dorner T, Doria A, Ferrario F, Floege J, Houssiau FA, Ioannidis JP, Isenberg DA, Kallenberg CG, Lightstone L, Marks SD, Martini A, Moroni G, Neumann I, Praga M, Schneider M, Starra A, Tesar V, Vasconcelos C, van Vollenhoven RF, Zakharova H, Haubitz M, Gordon C, Jayne D, Boumpas DT: Joint European League against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis 2012;71:1771-1782.
32.
Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, Karpouzas GA, Merrill JT, Wallace DJ, Yazdany J, Ramsey-Goldman R, Singh K, Khalighi M, Choi SI, Gogia M, Kafaja S, Kamgar M, Lau C, Martin WJ, Parikh S, Peng J, Rastogi A, Chen W, Grossman JM: American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken) 2012;64:797-808.
33.
Ruiz-Irastorza R, Espinosa G, Frutos MA, Jiménez Alonso J, Praga M, Pallarés L, Rivera F, Robles AM, Segarra A, Quereda C: Diagnóstico y tratamiento de la nefritis lúpica. Documento de consenso del grupo de enfermedades autoinmunes sistémicas (GEAS) de la Sociedad Española de Medicina Interna (SEMI) y de la Sociedad Española de Nefrología (SEN). Nefrología 2012;32(suppl 1):1-35.
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