Micofenolato de mofetilo en nefritis lúpica refractaria a ciclofosfamida intravenosa

Daza, Leonel; Pérez, Salvador; Velasco, Ulises; Hernández, Martha

doi:10.1016/S1699-258X(06)73055-8

Article information

Objetivo

Evaluar el uso del micofenolato de mofetilo (MMF) en pacientes con nefropatía lúpica (NL) y fracaso al tratamiento inicial con ciclofosfamida intravenosa (i.v.), durante un período de 12 meses.

Pacientes y métodos

Se incluyeron 11 pacientes con NL. La dosis de MMF fue de 1,5-2 g/día. Se midieron la depuración de creatinina, creatinina sérica y proteinuria en orina de 24 h; asimismo, se anotaron los episodios adversos con el tratamiento durante los 12 meses.

Resultados

La proteinuria basal disminuyó con MMF de 1,63 (intervalo de confianza [IC] del 95%, 0,78-2,5) a 0,93 g/l (IC del 95%, 0,1-1,62) en el doceavo mes, con un valor de p = 0,04. La depuración de creatinina tuvo una tendencia a la mejoría, sin embargo no hubo diferencia estadística, 69,2 (IC del 95%, 51,4-87,4) frente a 79,29 ml/min (IC del 95%, 49,2-109,3), con una p = 0,90. Las demás variables no mostraron diferencias significativas. Los pacientes que no respondieron a MMF tuvieron los índices de cronicidad más altos que los pacientes con respuesta buena o regular.

Conclusión

El MMF a dosis de 1,5-2,0 g/día es una buena alternativa en la NL con bajos índices de cronicidad y con fallo a la ciclofosfamida i.v., sin efectos colaterales graves.

Palabras clave:

Nefritis lúpica

Micofenolato mofetilo

Ciclofosfamida

Lupus eritematoso generalizado

Objective

To evaluate the use of mycophenolate mofetil (MMF) in lupus nephritis (LN) patients with prior failure to intravenous cyclophosphamide over a 12-month follow-up.

Patients and methods

Eleven patients with LN were included. MMF doses ranged from 1.5-2 grams per day. In all patients, 24-h urinary protein excretion, creatinine clearance, and serum creatinine were evaluated. Treatment-related adverse effects were recorded over the 12-month follow-up.

Results

Basal proteinuria decreased from 1.63 g/L (95% CI: 0.78-2.5) to 0.93 (95% CI: 0.1-1.62) g/L at the end of the follow-up period (p = 0.04). Creatinine clearance showed a tendency to improve but no statistically significant differences were found, 69.2 (95% CI 51.4- 87.4) vs. 79.29 (IC 95% 49.2-109.3) ml/min, respectively; p = 0.90). No significant differences were found in the remaining variables. Patients without response to MMF had a higher chronicity index than those with good or average response.

Conclusion

MMF doses of 1.5-2 grams per day are a good alternative in LN patients without response to intravenous cyclophosphamide and a low chronicity index. No severe adverse effects were found.

Key words:

Lupus nephritis

Mycophenolate mofetil

Cyclophosphamide

Systemic lupus erythematosus

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Bibliografía

[1.]

M.C. Carrol.

The lupus paradox: Natural immunity is protective against disease.

Kidney Int, 65 (2004), pp. 1540

[2.]

D. Pisetski.

Systemic lupus erythematosus, epidemiology, pathology and pathogenesis.

Primer on the rheumatic diseases, pp. 246-251

[3.]

L. Martins, G. Rocha, A. Rodríguez, J. Santos, C. Vasconcelos, J. Correia, et al.

Lupus nephritis: a retrospective review of 78 cases from a single center.

Clin Nephrol, 57 (2002), pp. 114-119

Medline

[4.]

S.M. Korbet, E.J. Lewis, M.M. Schwartz, M. Reichlin, J. Evans, R.D. Rohde.

Factors predictive of outcome in severe lupus nephritis. Lupus Nephritis Collaborative Study Group.

Am J Kidney Dis, 35 (2000), pp. 904-914

Medline

[5.]

R. Cervera, M. Khamashta, J. Font, G. Sebastián, A. Gil, P. Lavilla, The European Working Party on Systemic Lupus Erythematosus, et al.

Systemic lupus erythematosus: Clinical and immunologic patterns of disease expression in a cohort of 1,000 patients.

Medicine, 72 (1993), pp. 113-124

Medline

[6.]

M. Abu Shakra, M. Urowitz, D. Gladman, J. Gough.

Mortality studies in systemic lupus erythematosus results from a single center. I. Causes of death.

J Rheumatol, 22 (1995), pp. 1259-1264

Medline

[7.]

R. Herrera-Esparza, O. Barbosa, H. Villalobos, E. Avalos.

Renal expression of IL-6 and TNF alpha genes in lupus nephritis.

Lupus, 7 (1998), pp. 134-138

[8.]

I. Badillo-Almaraz, L. Daza, E. Avalos-Díaz, R. Herrera-Esparza.

Glomerular expression of FAS ligand and BAX mRNA in lupus nephritis.

Autoimmunity, 34 (2001), pp. 283-289

Medline

[9.]

H.A. Austin III, J.H. Klippel, J.E. Balow, N.G. Le Riche, A.D. Steinberg, P.H. Plotz, et al.

Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs.

N Engl J Med, 314 (1986), pp. 614-619

http://dx.doi.org/10.1056/NEJM198603063141004 | Medline

[10.]

M.F. Gourley, I.II. Austin HA, D. Scott, C.H. Yarboro, E.M. Vaughan, J. Muir, et al.

Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial.

Ann Intern Med, 125 (1996), pp. 549-557

Medline

[11.]

R.E. Bullingham, A.J. Nicholls, B.R. Kamm.

Clinical pharmacokinetics of mycophenolate mofetil.

Clin Pharmacokinetics, 34 (1998), pp. 429

[12.]

A.C. Allison, E.M. Eugui.

Mycophenolate mofetil and its mechanisms of action.

Immunopharmacology, 47 (2000), pp. 85

Medline

[13.]

C.A. Jonsson, H. Carlsten.

Mycophenolic acid inhibits inosine 5’-monophosphate dehydrogenase and suppresses production of pro-inflammatory cytokines, nitric oxide, and LDH in macrophages.

Cell Immunol, 216 (2002), pp. 93-101

Medline

[14.]

G. Contreras, V. Pardo, B. Leclercq, O. Leonz, E. Tozman, P. O’Nan, et al.

Sequential therapies for proliferative lupus nephritis.

N Engl J Med, 350 (2004), pp. 971-980

http://dx.doi.org/10.1056/NEJMoa031855 | Medline

[15.]

J. Cross, A. Dwomoa, P. Andrews, A. Burns, C. Gordon, J. Main, Renal Association Clinical Trials Subcommittee, et al.

Mycophenolate mofetil for remission induction in severe lupus nephritis.

Nephron Clin Pract, 100 (2005), pp. c92-c100

http://dx.doi.org/10.1159/000085054 | Medline