New therapies in steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome

Abstract

Although many children with idiopathic nephrotic syndrome (INS) respond initially to steroid therapy, repeated courses for patients with relapses often cause significant steroid toxicity. Patients with frequent relapses who develop steroid dependency thus require alternative treatment. The first such options have been considered to be cyclophosphamide or levamisole, although the latter is no longer available in many countries. There is also an increasing body of data indicating that mycophenolic acid (MPA) may be an alternative for these patients. Calcineurin inhibitors (cyclosporine A or tacrolimus) are usually effective and often used after cytotoxic treatment, but long-term treatment with these agents is necessary, raising concerns of a possible accumulation of side effects. Some patients show a tendency to relapse even on such maintenance regimens, and some even have a refractory course that creates a medical dilemma. For this situation, recent data indicate that monoclonal antibodies directed to B-cells (e.g. rituximab) may have some effect and that such drugs may also prove to be a therapeutic option in less complicated cases. Patients that do not respond to steroid treatment need genetic testing and a renal biopsy since focal segmental glomerulosclerosis (FSGS) may be present. Treatment options include pulse methylprednisolone, often in addition to calcineurin inhibitors, mainly in the form of cyclosporine, but tacrolimus has also come into recent favor. Some studies have found cytotoxic treatment, especially intravenous cyclophosphamide, to be effective in steroid resistant nephrotic syndrome, but it seems to be inferior to calcineurin inhibitors. MPA and rituximab have also been used in children with primary FSGS, but the response seems to be inferior to that in patients with steroid sensitive nephrotic syndrome. Taken together, INS in both steroid-sensitive and steroid-resistant patients is a potentially complicated disorder, and despite a wide arsenal of immunological interventions, some patients have a treatment refractory course. Prospective studies or at least standardized treatment for complicated cases is urgently needed.

Clinical Course of Steroid Sensitive Nephrotic Syndrome in Children: Outcome and Outlook

“…As demonstrated in our analysis, the application of the alkylating agents has led to favorable clinical courses of SSNS; the similar results are also reported in [3,14,23,28]. As usually recommended, first line CYC I.V.…”

Two-Year Follow-Up of a Prospective Clinical Trial of Cyclosporine for Frequently Relapsing Nephrotic Syndrome in Children

“…No lethal events occurred during the approximately 4 years from the beginning of cyclosporine treatment in any participant, and only one patient developed a very mild decrease in renal function. Growth in terms of height was also maintained or slightly improved during the 4 years in spite of relapses and the (24). Whereas the efficacy of cyclosporine remains clear, we speculate that in addition to prolonged or repeated administration of cyclosporine, the combination of several immunosuppressants given in sequence should also be considered.…”

“…Whereas the efficacy of cyclosporine remains clear, we speculate that in addition to prolonged or repeated administration of cyclosporine, the combination of several immunosuppressants given in sequence should also be considered. Recent attention has focused on the efficacy of several emerging immunosuppressants, including tacrolimus (24,25) and rituximab (24,26), in controlling relapse, and both are now under evaluation in children with FRNS in a multicenter, prospective, randomized fashion in Japan. In addition to the control of relapse, long-term management must also consider any adverse effects of therapy as well as the growth and quality of life of children.…”

Consenso de tratamiento del síndrome nefrótico en la infancia

“…[42][43][44][45][46] Los últimos resultados publicados aportan una remisión de la proteinuria en un 80% en pacientes corticorresistentes con esclerosis focal. [46][47][48] Otras recomendaciones para el tratamiento de pacientes que no responden a la ciclofosfamida son ácido micofenólico, tacrolimos y rituximab. En este sentido, solo hay experiencias con muy poco número de pacientes.…”

“…En este sentido, solo hay experiencias con muy poco número de pacientes. 48 tratamiento del edema Indicaciones generales • Dieta hiposódica.…”