IMPORTANCE Calcineurin inhibitors are an established first-line corticosteroid-sparing therapy for patients with corticosteroid-dependent nephrotic syndrome (CDNS), whereas B-lymphocyte-depleting therapy is mostly used as a rescue for calcineurin inhibitor-resistant cases. The positive efficacy and safety profile of rituximab raises the question of whether it could be used as a first-line alternative to calcineurin inhibitor therapy. OBJECTIVE To compare the efficacy of rituximab and tacrolimus in maintaining relapse-free survival among children with CDNS. DESIGN, SETTING, AND PARTICIPANTS A parallel-arm, open-label, randomized clinical trial was performed from May 8, 2015, to September 20, 2016, with 1-year follow-up in a single-center, tertiary care unit. A total of 176 consecutive children aged 3 to 16 years with CDNS not previously treated with corticosteroid-sparing agents were screened for eligibility. INTERVENTIONS The children received either tacrolimus (along with tapering alternate-day prednisolone) for 12 months or a single course of rituximab (2 infusions of 375 mg/m 2). MAIN OUTCOMES AND MEASURES Twelve-month relapse-free survival in the intention-to-treat population. RESULTS Of the 176 children screened for eligibility, 120 were randomized and all but 3 patients completed 1 year of follow-up. The groups were comparable, with mean (SD) age of 7.2 (2.8) years, 32 boys (53.3%) in each group, mean (SD) disease duration of 2.5 (1.5) years and 2.3 (1.7) in the tacrolimus and rituximab groups, respectively, disease duration less than 1 year among 15 children (25.0%) in each group, median (interquartile range) of 4 (3-5) relapses in each group, and mean (SD) cumulative prednisolone dose of 246 (48) mg/kg and 239 (52) mg/kg in the prestudy year in the tacrolimus and rituximab groups, respectively. Rituximab therapy was associated with a higher 12-month relapse-free survival rate than tacrolimus (54 [90.0%] vs 38 [63.3%] children; P < .001; odds ratio, 5.21; 95% CI, 1.93-14.07). Among the patients who experienced relapse, median time to first relapse was 40 weeks in the rituximab group and 29 weeks in the tacrolimus group. Only 2 patients in the rituximab group had more than 1 relapse during the study period compared with 10 patients in the tacrolimus group. The cumulative corticosteroid dose during the 12-month study period was lower with rituximab compared with tacrolimus (mean [SD], 25.8 [27.8] vs 86.3 [58.0] mg/kg). Although both treatments were well tolerated, mild to moderate infections were twice as common in the tacrolimus group (26 [43.3%] vs 13 [21.7%] events). CONCLUSIONS AND RELEVANCE In children with CDNS, rituximab appears to be more effective than tacrolimus in maintaining disease remission and minimizing corticosteroid exposure and, given its good tolerability and lack of nephrotoxic effects, may be considered as first-line corticosteroid-sparing therapy.
The baseline data of this large pediatric cohort show that surrogate markers for cardiovascular disease are closely associated with systolic hypertension and stage of CKD.
Objective and aim Severe cases of bone atrophy in the maxilla or mandible are often reconstructed using bone from extraoral donor sides. Most commonly, grafts from the iliac crest are used for augmentation, however, frequently associated with bone resorption as possible late complication. Calvarial bone grafts, often reported to show less resorption, are an alternative. The aim of this study was to compare the bone stability of vertical bone grafts from the iliac crest and the calvarium. Patients and methods Twenty‐three patients receiving vertical onlay bone grafts were included in this retrospective cohort study. In nine patients alveolar ridge defects were treated with bone from the iliac crest. Fourteen patients were reconstructed using calvarial bone grafts. To quantify bone resorption, the data of digital panographs were evaluated. Radiographs were taken prior to bone grafting, after augmentation surgery, 6 months after bone healing, prior to implant surgery, after implant surgery and at yearly intervals thereafter. Results Postoperative complications at the recipient site occurred equally in both groups. The complication rate was 35.7% for the calvarial group and 33.3% in the iliac crest group. No donor‐site complications were reported in either group. After bone augmentation procedure, a mean vertical bone gain of 8.55 mm (SD 5.96) was measured. Bone grafts from the iliac crest showed a significantly higher bone loss of 24.16% (SD 8.47) than grafts from the calvarium (8.44%, SD 3.64) at the time of implant placement (P = 0.0003). Implant survival was similar in both groups. Discussion Both bone‐grafting approaches are successful and reliable techniques, enabling implant placement in even highly atrophied alveolar ridges and with identical implant survival rates, although bone resorption differs. Within the limitations of this study bone from the calvarium shows higher bone stability in the early healing phase.
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