Uncertainty in management of childhood-onset idiopathic nephrotic syndrome: is the long-term prognosis really favorable?

Abstract

Despite the recent establishment of clinical practice guidelines, many areas in the management of childhood idiopathic nephrotic syndrome (INS) remain uncertain. In this edition of Pediatric Nephrology Samuel et al. report significant differences between Canadian pediatric nephrologists' practice and guideline recommendations, including initial duration of glucocorticoid treatment, choice of glucocorticoid-sparing agents in cases of frequently relapsing or steroid-dependent INS, and biopsy timing. Although evidence is emerging that the incidence of subsequent relapse can be reduced with longer initial glucocorticoid therapy, even with this new regimen relapse occurs in more than half of the children with steroid-sensitive INS. Cyclosporine (CsA) as a glucocorticoid-sparing agent for children with frequently relapsing or steroid-dependent INS is believed to provide protection from steroid toxicity and significantly improve the quality of life. However, recent follow-up studies of the post-CsA era have revealed a high incidence of INS relapse in adulthood in patients treated with CsA in childhood, and CsA use itself is a significant predictor of recurrent relapses. Therefore, pediatric nephrologists must recognize the potential of adverse effects that may appear later in life because of prolonged immunosuppressive therapy in childhood.

Toll-like receptor 3 expression and function in childhood idiopathic nephrotic syndrome

“…Relapses are frequent after withdrawal of steroid treatment, with up to 60% of patients being steroid‐dependent. Immunosuppressive treatments, such as cyclophosphamide and calcineurin inhibitors, are administered as a second‐line treatment for INS to prevent relapses and to spare steroid usage . Rituximab (RTX), a chimeric human–mouse anti‐CD20 monoclonal antibody, is also effective in the treatment of INS in preventing relapses in steroid‐dependent patients .…”

Treatment of children with frequently relapsing steroid-sensitive nephrotic syndrome: recent trial results

“…Cyclophosphamide shows higher efficacy in FRNS than in SDNS [36]. Recent data confirm that poor outcome regarding relapses is associated with young age, male sex and FSGS [37,38]. Additionally, in patients with SDNS requiring high dosage of corticosteroids to maintain remission cyclophosphamide is less effective [39].…”

“…Prolonged courses of CsA reduce the risk of relapse in children with FRNS compared with corticosteroids alone [33], as well as compared with alkylating agents [31,32], but children with FRNS or SDNS are at high risk of relapse after discontinuation, particularly those who experienced relapse during CsA treatment [42]. CsA administration by itself is a significant predictor of relapse in adulthood [37,43,44]. The length of treatment with CsA remains controversial, but most centers try to taper the medication after 1-3 relapse-free years.…”

Management des steroidsensiblen nephrotischen Syndroms im Kindes- und Jugendalter

“…Die aktuelle Behandlung der Erstmanifestation des nephrotischen Syndroms erfolgt nach der Standardinitialtherapie der GPN (3): (22)(23)(24). Cyclophosphamid stellt in dieser Indikation im Gegensatz zu anderen Alternativmedikationen einen potenziell kurativen Behandlungsansatz dar.…”