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Both levamisole and mycophenolate mofetil (MMF) prevent relapses in patients with frequently relapsing nephrotic syndrome; however, their efficacy has not been compared prospectively. This single-center, randomized, open-label trial enrolled 149 children ages 6-18 years with frequently relapsing or steroid-dependent nephrotic syndrome. Participants were randomized in a 1:1 ratio to receive therapy with MMF (750-1000 mg/m2 daily) or levamisole (2-2.5 mg/kg on alternate days) for 1 year; prednisolone was discontinued by 2-3 months. In intention-to-treat analyses, the frequency of relapse was similar between participants treated with MMF and levamisole (mean difference -0.29 relapses/patient-year; 95% confidence interval -0.65, 0.08). Relapse rates declined to almost one-third of baseline for both treatment groups. Therapy with MMF was not superior to levamisole in terms of the proportions of participants with sustained remission (40.8% vs. 34.2%), frequent relapses (14.5% vs. 16.4%), or treatment failure, a composite outcome of frequent relapses, steroid resistance, or significant steroid toxicity (15.8% vs. 20.6%). These outcomes were also similar in time to event analyses. Changes in anthropometry and blood pressure were similar between the groups, and the rates of adverse effects were low in both groups. Flow cytometry in 32 participants demonstrated similar proportions of B cells and CD4+, CD8+, T helper (Th)1, Th2, Th17, and T regulatory (Treg) cells during follow-up. Therapy with MMF was not superior to levamisole in the frequency of relapses, likelihood of sustained remission or corticosteroid sparing in children with frequently relapsing or steroid-dependent nephrotic syndrome. Registration CTRI/2012/02/002394

In this prospective study, we measured serum levels of the soluble urokinase receptor (suPAR) in pediatric patients with nephrotic syndrome of various etiologies. Mean levels of suPAR were 3316pg/ml in 99 patients with steroid-resistant focal segmental glomerulosclerosis and 3253pg/ml in 117 patients with biopsy-proven minimal change disease, which were similar to that of 138 patients with steroid-sensitive nephrotic syndrome (3150pg/ml) and 83 healthy controls (3021pg/ml). Similar proportions of patients in each group had suPAR over 3000pg/ml. Compared with controls, suPAR levels were significantly higher in patients with focal segmental glomerulosclerosis (FSGS) and estimated glomerular filtration rate (eGFR) under 30ml/min per 1.73m 2 (6365pg/ml), congenital nephrotic syndrome (4398pg/ml), and other proteinuric diseases with or without eGFR under 30ml/min per 1.73m 2 (5052 and 3875pg/ml, respectively; both significant). There were no changes following therapy and during remission. Levels of suPAR significantly correlated in an inverse manner with eGFR ( r =-0.36) and directly with C-reactive protein ( r =0.20). The urinary suPAR-to-creatinine ratio significantly correlated with proteinuria ( r =0.25) in 151 patients and controls. Using generalized estimating equations approach, serum suPAR significantly correlated with eGFR (coefficient=-13.75), age at sampling (2.72), and C-reactive protein (39.85). Thus, serum suPAR levels in nephrotic syndrome are similar to controls, and do not discriminate between FSGS, minimal change disease, or steroid-responsive illness.