IPNA clinical practice recommendations for the diagnosis and management of children with steroid-sensitive nephrotic syndrome

Abstract

Idiopathic nephrotic syndrome is the most frequent pediatric glomerular disease, affecting from 1.15 to 16.9 per 100,000 children per year globally. It is characterized by massive proteinuria, hypoalbuminemia, and/or concomitant edema. Approximately 85–90% of patients attain complete remission of proteinuria within 4–6 weeks of treatment with glucocorticoids, and therefore, have steroid-sensitive nephrotic syndrome (SSNS). Among those patients who are steroid sensitive, 70–80% will have at least one relapse during follow-up, and up to 50% of these patients will experience frequent relapses or become dependent on glucocorticoids to maintain remission. The dose and duration of steroid treatment to prolong time between relapses remains a subject of much debate, and patients continue to experience a high prevalence of steroid-related morbidity. Various steroid-sparing immunosuppressive drugs have been used in clinical practice; however, there is marked practice variation in the selection of these drugs and timing of their introduction during the course of the disease. Therefore, international evidence-based clinical practice recommendations (CPRs) are needed to guide clinical practice and reduce practice variation. The International Pediatric Nephrology Association (IPNA) convened a team of experts including pediatric nephrologists, an adult nephrologist, and a patient representative to develop comprehensive CPRs on the diagnosis and management of SSNS in children. After performing a systematic literature review on 12 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, recommendations were formulated and formally graded at several virtual consensus meetings. New definitions for treatment outcomes to help guide change of therapy and recommendations for important research questions are given.

Immunosuppressive Agent Options for Primary Nephrotic Syndrome: A Review of Network Meta-Analyses and Cost-Effectiveness Analysis

“…As most pediatric NS is treated without renal biopsy and considered to represent MCNS, the pathological type of NS is not always diagnosed before treatment. Therapeutic algorithms have therefore been described for steroid-sensitive or -resistant NS [ 28 , 37 ]. The initial treatment of pediatric NS is prednisolone based on the guidelines.…”

“…This review therefore discusses the characteristics of regions. Use of levamisole (LEV) is unique to NS in children living in certain countries, including India [ 40 , 41 ], as broadly described in guidelines [ 1 , 25 , 26 , 27 , 28 ]. That RCTs are needed to clarify the role of LEV in frequently relapsing/steroid-dependent MCNS in adults was mentioned in KDIGO 2012 through to KDIGO 2021.…”

“…Very few well-designed comparative studies of LEV for NS in adults have been reported, but the proposed molecular mechanisms appear to be supported by an experiment using puromycin-aminonucleoside-treated cells [ 42 , 43 ]. For Japanese children, three immunosuppressive agents commonly used in the treatment of frequently relapsing and steroid-dependent NS are CsA, CPA, and MZB, instead of the MMF listed in international guidelines [ 23 , 26 , 28 ]. In adults, apart from in MCNS and idiopathic MN, use of RTX in FSGS is not recommended in KDIGO guidelines, while Japan allows the use of RTX in steroid-dependent frequently relapsing NS, including FSGS, if the condition of childhood onset is met [ 24 ].…”

“…Guidelines differ in the recommendations or indications for therapeutic agents depending on when they were published and the country from which they were issued [ 1 , 23 , 24 , 25 , 26 , 27 , 28 ]. A previous descriptive NS classification, based largely on histological patterns, is increasingly being replaced on the basis of new pathogenic insights [ 3 ].…”

Nephrotic syndrome in children: international evidence and Ukraine 2022

“…Метою даної роботи став огляд актуальних рекомендацій щодо конверсійної терапії дітей з нефротичним синдромом та визначення особливостей терапевтичного супроводу цієї когорти в Укра-їні. Проведено аналіз настанов KDIGO 2021 [2] та рекомендацій IPNA 2020 і 2023 [3,4], співставлення з діючим в Україні протоколом лікування дітей з НС [5]. Вивчено правову базу застосування міжнародного досвіду в медичній практиці країни [6].…”