RESUMO
BACKGROUND: 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. 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). METHODS: This 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. RESULTS: There 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. CONCLUSION: Majority 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%.
