The Need for a Children's Oncology Group–Oriented Approach to Advance the Care of Children with Idiopathic Nephrotic Syndrome

Abstract

diopathic nephrotic syndrome (INS) affects 16 per 100,000 children, making this condition one of the most common childhood kidney diseases. Because of the significant com- plications associated with INS and its treatments in children, childhood INS remains a daunting challenge for children, fam- ilies, and medical professionals. Amazingly, the approach to childhood INS today is still based on decades-old pivotal stud- ies that were impressive in scope but have limited applicability to the clinical challenges faced by pediatric nephrologists to- day. These foundational studies began with an international collaborative effort sponsored by the International Study of Kidney Disease in Children (ISKDC) (1). From 1967 to 1974, 521 children with new-onset INS underwent renal biopsies and standard prednisone treatment to demonstrate that normaliza- tion of urine protein excretion with 8 wk of corticosteroid therapy is predictive of minimal-change nephrotic syndrome (2). As a result, pediatric nephrologists began using the initial therapeutic response to glucocorticoids to guide the subsequent evaluation and therapy for children who present with INS. This sentinel work of the ISKDC was followed by a series of studies by the Arbeitsgemeinschaft fur Padiatrische Nephrologie, which together form the basis for modern practice treatment of children with INS (3-5). Of note, these landmark studies are also almost 20 yr old, but the clinical characteristics and chal- lenges of children who present with INS have clearly changed in recent decades. For example, the incidence of FSGS in chil- dren with INS has increased dramatically (6); children in the United States have a rapidly increasing prevalence of obesity and type 2 diabetes, which may be exacerbated by our standard treatments with glucocorticoids (7); and the importance of de- mographic status and treatment compliance in patient out- comes is being increasingly recognized (8). In 2008, a survey regarding treatment of childhood INS among North American pediatric nephrologists at 10 US cen- ters was performed. That survey highlighted significant dispar- ities among practitioners, including wide practice variations in even the most fundamental aspects of care, such as the man- agement of initial presentations, relapses, and steroid resistance in children with INS (9). In this context, the North American Children's Nephrotic Syndrome Consensus Conference was convened to develop updated evidence- and opinion-based recommendations for the evaluation and treatment of children with INS for North American pediatric nephrologists (10). In that consensus conference report, only a limited number of treatment recommendations could be based on class 1 evidence; recommendations related to extent of evaluation, monitoring for complications, and treatment for steroid-dependent and steroid-resistant NS almost all were based on small case series and expert opinion. Of note, despite the 344 published original investigations reviewed during this process, only three of the 86 articles cited in that consensus conference report involved 10 yr of outcome follow-up in children with INS. This sober- ing reality emphasizes the value of the study of Kyrieleis et al. (11) in this month's CJASN, which addresses the long-term outcome of frequently relapsing minimal-change nephrotic syndrome in children and focuses on the effectiveness of con- tinued immunosuppression and the complications of these agents in this population. In this report, at least 10 yr of fol- low-up is provided for all 15 patients with steroid-responsive INS that presented in childhood. All had at least one relapse after 16 yr of age, and the long follow-up offers insights into the ongoing treatment responsiveness in these children. Although this article indicates that corticosteroid responsiveness may persist for many years in some children, particularly in combi- nation with second-line agents such as calcineurin inhibitors, complications are common and the risk-benefit ratios of treat- ments are unexplored. Although this report is only observa- tional, it does reinforce the value and usefulness of detailed long-term observational studies of these children. Because the vast majority of our patients will survive to adulthood, there is a distinct need for studies of the long-term outcomes (and