Abstract
BackgroundMajority of children with nephrotic syndrome are steroid sensitive, but treatment of difficult to treat nephrotic (frequent relapsing, steroid dependent and steroid resistant) syndrome is challenging. Low dose steroid, levamisole, cyclophosphamide (CPM), mycophenolate mofetil (MMF) and calcineurin inhibitors (CNIs) are the common options of treatment.Objective of the study was to determine the response to steroid and alternative immunosuppressive agents (ISAs) in children with difficult nephrotic syndrome (DNS).MethodsThis is a retrospective cohort study of 176 children with DNS, managed over 12 years at The Kidney Center-Postgraduate Training Institute, Karachi- Pakistan from 2005 to 2017.Initial episode was treated with daily oral prednisolone (OP) for 4–8 weeks followed by alternate day OP for 12–24 weeks. Subsequently low dose OP, levamisole (Leva)and cyclophosphamide was used for frequent relapsing (FR)/ steroid dependent (SD). All with initial steroid resistance and non- responders to leva and or cyclophosphamide were biopsied and treated with CNIs and MMF. Data was analyzed using descriptive statistics.ResultsThere were 130(73.86%) children with FR/SD and 46(26.13%) with SRNS. All children with SR (46) and 86 with FR/SD were biopsied. Minimal change disease (60.60%) and focal segmental glomerulosclerosis (FSGS 23%) were the two common lesions. Majority (73.86%) received single OP whereas divided doses were administered in 26.13% cases. Daily OP was used for 4, 6 and 8 weeks in 61.36,28.4 and10.22% respectively. Steroids were tapered over 3 (31.81%),4 (52.27%) and 6 months (15.90%). Levamisole, CPM, cyclosporin (CS) and MMF were used sequentially in 45, 54.23, 50 and 20% respectively. Combination of MMF and CS was used in 11.29% of cases.Levamisole was effective in 80%, CPM induced complete remission (CR, 57.77%) or partial remission (PR, 22.22%), CS induced CR 46.59% and PR 39.77%. MMF showed PR and CR 69 and 12.82% respectively. At last follow up, 46% were maintaining remission while off treatment, whereas 35% are maintaining remission on therapy,10.23% lost- to-follow, 5.68% progressed to chronic kidney disease. Mortality was 2.84% and it was due to infection and uremia.ConclusionMajority had steroid sensitive MCD. Levamisole and cyclophosphamide were effective in maintaining remission in FR/ SD. FSGS was responsible for resistance to steroid and alternative ISAs. Cyclosporin was effective in inducing remission in SRNS. Mortality was less than 3%.
Highlights
Majority of children with nephrotic syndrome are steroid sensitive, but treatment of difficult to treat nephrotic syndrome is challenging
This study describes the various aspects of management of difficult nephrotic syndrome (DNS) including the clinical and biochemical characteristics, varying steroid protocols, patient’s initial and subsequent behavior to steroids and frequency of relapses based out come in the form of either frequent relapsing (FR)/steroid dependent (SD) or
Our results show that majority of patients (73.86%) were initial steroid sensitive which behaved as FR/SD requiring sequential multi-strategic therapies and 26.13% of patients were either early or late steroid resistant (SR)
Summary
Majority of children with nephrotic syndrome are steroid sensitive, but treatment of difficult to treat nephrotic (frequent relapsing, steroid dependent and steroid resistant) syndrome is challenging. International Study of Kidney Disease in Children (ISKDC) in early 70s recommended daily oral steroid 60 mg/m2 for 4 weeks followed by 40 mg /m2 on alternate day for 4 weeks [1]. Use of high dose steroid (60 m2/day) for 6 weeks followed by 40 mg/m2 on alternate day for 6 weeks showed reduction in frequency of relapses and steroid dependency [2]. Kidney Disease Initiative Global Outcome (KDIGO) guidelines (2012) suggested same dose with more flexibility of using oral prednisolone (OP) 60 mg/m2/day for 4–6 weeks followed by tapering over 2–5 months [3]. More than 85–90% of children are initial steroid sensitive and achieve remission within 4–6 weeks and 10–15% behave as initial steroid resistant (SR) [1, 3, 7]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
