Eficacia y seguridad del tratamiento combinado con ciclosporina A y micofenolato de mofetilo en enfermos con glomeruloesclerosis segmentaria y focal ciclosporina-resistente / Efficacy and safety of combined cyclosporin A and mycophenolate mofetil therapy in patients with cyclosporin-resistant focal segmental glomerulosclerosis

Introducción: La asociación de ciclosporina A (CsA) y micofenolato mofetil (MMF) tiene un efecto inmunosupresor sinérgico y, en consecuencia, podría inducir una remisión del síndrome nefrótico en enfermos con glomeruloesclerosis segmentaria y focal resistente a esteroides y a CsA. Objetivo: Analizar la eficacia y el perfil de seguridad de la asociación CsA y MMF en enfermos con GSF resistente a ciclosporina A. Pacientes y método: 27 enfermos con GSF resistente a CsA recibieron tratamiento con CsA (4 mg/kg/día) asociada a MMF (2 g/día) durante 12 meses. El seguimiento total fue de 5 años. Como medida de resultado, se consideró la proporción de enfermos con remisión de la proteinuria y la evolución de la función renal a los 5 años. Resultados: Al finalizar el período de tratamiento, ningún paciente presentó remisión completa; 4 pacientes (14,8%) presentaron reducción de proteinuria a valores <3,5 g/día. Estos enfermos presentaban proteinuria basal (5,62 ± 2,19 frente a 8,1 ± 2,96 g/día, p = 0,042) y pendientes de FG (-0,08 ± 0,12 frente a -0,69 ± 0,38; p = 0,003) significativamente inferiores y mayor función renal basal (99,6 ± 12,9 frente a 85,05 ± 15,5 ml/min; p = 0,003). Dieciséis de los 27 enfermos (59,2%) presentaron una enfermedad renal progresiva o estadio V al final del período de seguimiento. Se apreciaron efectos adversos gastrointestinales en el 33,3% de los enfermos y nefrotoxicidad aguda transitoria en el 14,8%. El 22,2% de los enfermos precisó un incremento en la dosis y/o número de hipotensores durante los 12 meses de tratamiento. Conclusiones: En enfermos con GSF resistente a ciclosporina, el tratamiento con asociación de CsA y MMF durante 12 meses, aunque puede inducir reducciones parciales de la proteinuria, no modifica significativamente el curso evolutivo de la función renal (AU)

Introduction: The combination of cyclosporin A (CsA) and mycophenolate mofetil (MMF) has a synergistic immunosuppressive effect and, as a result, it may induce remission of nephrotic syndrome in patients with steroid- and CsA-resistant focal segmental glomerulosclerosis (FSGS). Objective: To analyse the efficacy and safety of the combined CsA and MMF treatment in patients with cyclosporin A-resistant FSGS. Patients and methods: Twenty-seven patients with CsA-resistant FSGS were treated for 12 months with CsA (4 mg/kg/day) combined with MMF (2 g/day). The overall follow-up was 5 years. The proportion of patients with remission of proteinuria and the evolution of kidney function after 5 years were used to measure the outcome. Results: At the end of the treatment period, no patients were in complete remission and 4 patients (14.8%) had reduced proteinuria to values <3.5g/day. These patients had significantly lower baseline proteinuria (5.62±2.19 compared to 8.1±2.96g/day, P=.042), significantly lower GFR (-0.08 compared to -0.69±0.38; P=.003) and higher baseline kidney function (99.6±12.9 compared to 85.05±15.5ml/min; P=.003). Sixteen out of the 27 patients (59.2%) had progressive or stage 5 kidney disease at the end of the follow-up period. Adverse gastrointestinal effects were observed in 33.3% of the patients and acute transitory nephrotoxicity in 14.8%. The dosage and/or number of anti-hypertensive drugs had to be increased in 22.2% of patients during the 12 months of treatment. Conclusions: Twelve months of combined CsA and MMF therapy does not significantly alter the evolution of kidney function in patients with cyclosporin-resistant FSGS, although it may induce partial reductions in proteinuria (AU)

Efficacy and safety of combined cyclosporin A and mycophenolate mofetil therapy in patients with cyclosporin-resistant focal segmental glomerulosclerosis.

INTRODUCTION: The combination of cyclosporin A (CsA) and mycophenolate mofetil (MMF) has a synergistic immunosuppressive effect and, as a result, it may induce remission of nephrotic syndrome in patients with steroid- and CsA-resistant focal segmental glomerulosclerosis (FSGS). OBJECTIVE: To analyse the efficacy and safety of the combined CsA and MMF treatment in patients with cyclosporin A-resistant FSGS. PATIENTS AND METHODS: Twenty-seven patients with CsA-resistant FSGS were treated for 12 months with CsA (4mg/kg/day) combined with MMF (2g/day). The overall follow-up was 5 years. The proportion of patients with remission of proteinuria and the evolution of kidney function after 5 years were used to measure the outcome. RESULTS: At the end of the treatment period, no patients were in complete remission and 4 patients (14.8%) had reduced proteinuria to values <3.5g/day. These patients had significantly lower baseline proteinuria (5.62±2.19 compared to 8.1±2.96g/day, P=.042), significantly lower GFR (-0.08 compared to -0.69±0.38; P=.003) and higher baseline kidney function (99.6±12.9 compared to 85.05±15.5ml/min; P=.003). Sixteen out of the 27 patients (59.2%) had progressive or stage 5 kidney disease at the end of the follow-up period. Adverse gastrointestinal effects were observed in 33.3% of the patients and acute transitory nephrotoxicity in 14.8%. The dosage and/or number of anti-hypertensive drugs had to be increased in 22.2% of patients during the 12 months of treatment. CONCLUSIONS: Twelve months of combined CsA and MMF therapy does not significantly alter the evolution of kidney function in patients with cyclosporin-resistant FSGS, although it may induce partial reductions in proteinuria.