Efficacy of body weight vs body surface area-based prednisolone regimen in nephrotic syndrome.

BACKGROUND: Prednisolone dosing regimen based on body surface area (BSA) or body weight (BW) in managing uncomplicated nephrotic syndrome (NS) has been a matter of controversy. METHODS: In this parallel-arm randomized clinical trial, 60 children with uncomplicated NS in relapse were randomized to receive either of two regimens. Children of BW cohort received prednisolone (2 mg/kg/day) till remission (or 6 weeks for first episode); followed by 1.5 mg/kg on alternate days for 4 weeks (or 6 weeks for first episode). Children randomized for BSA cohort received prednisolone (60 mg/m2/day) till remission (or 6 week for first episode); followed by 40 mg/m2 on alternate days for 4 weeks (or 6 weeks for first episode). The primary endpoint was 6-month relapse-free survival in the intention-to-treat population (clinical trial registry of India CTRI/2015/03/005655). RESULTS: The 6-month relapse-free survival rates were similar for both BSA cohort 73.33% (22/30) and BW cohort 70% (21/30) (p = 1, OR 0.19, 95% CI 0.07-0.52). Requirement of cumulative steroid to achieve initial remission (96.1 ± 57.8 vs 63.58 ± 40.2 mg/kg, p = 0.014) and over 6-month study period (104.34 ± 50.82 vs 73.88 ± 42.95 mg/kg, p = 0.015) were significantly higher in BSA cohort in comparison to BW cohort. However, time taken in achieving remission during enrolment episode in both BSA and BW groups was comparable (7 ± 1.7 vs 6.9 ± 1.4 days, p = 0.81). While both treatments were well tolerated, the number of adverse events was one and half times as common in the BSA group than BW group (37 vs. 22 events). CONCLUSIONS: In treating children with uncomplicated NS, both BSA and BW regimens were equally effective in achieving initial remission and maintaining disease remission. Due to fewer adverse events and lesser cumulative steroid exposure with BW based regimen, it may be considered as better option over BSA regimen. CLINICAL TRIAL REGISTRY NAME: Clinical Trial Registry of India (CTRI/2015/03/005655).

Efficacy of Rituximab vs Tacrolimus in Pediatric Corticosteroid-Dependent Nephrotic Syndrome: A Randomized Clinical Trial.

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/m2). 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. Trial Registration: ClinicalTrials.gov Identifier: NCT02438982; Clinical Trial Registry of India: CTRI/2014/01/004355.

Acute Renal Failure Adversely Affects Survival in Pediatric Dengue Infection.

AIMS: Dengue is currently one of the most important mosquito-borne viral infections. Acute renal failure (ARF) is a serious complication among children suffering from dengue infection. SUBJECTS AND METHODS: A retrospective cohort review of baseline characteristics, disease outcomes, and risk factors of dengue-infected patients, with and without renal failure (RF), were compared. RESULTS: Among 97 children with dengue, 13.4% had RF (estimated glomerular filtration rate <60 ml/min/1.73 m2) at presentation. In comparison to all children (100%) of RF cohort, only 32% children of non-RF cohort (P < 0.0001) were suffering either from dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). The 7-day survival rate was 61.5% (8/13) among RF group as compared to 96.4% (81/84) in non-RF group (P < 0.001). When a fraction of patients who needed vasopressor support were significantly higher in RF cohort (70% vs. 14% for RF and non-RF, respectively, P < 0.001), requirement of mechanical ventilation (15% vs. 11%, P = 0.67) was comparable in both cohorts. CONCLUSIONS: DHF/DSS is an independent risk factor for the development of ARF in patients with dengue infection. Mortality rate is high once RF develops in these children.

Efficacy and safety of rituximab in comparison with common induction therapies in pediatric active lupus nephritis.

BACKGROUND: Childhood-onset lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE). Despite treatment-related toxicities, cyclophosphamide (CYC) and glucocorticoid-based treatment protocols are still considered standard therapy in managing this multisystem disorder. An effective and safe alternative induction regimen is needed. METHODS: Forty-four pediatric patients with active LN aged 3.5-13.8 (median 8.4) years, of whom 32 entered the study at diagnosis of SLE, were followed over 36 months. Induction therapy consisted of methylprednisolone pulses followed by either rituximab (RTX) (n = 17), mycophenolate mofetil (MMF) (n = 12) or pulse-CYC (n = 15), with tapering dose of prednisolone orally. MMF was added as maintenance immunosuppressant (800 mg/m2 daily) in all children from the third month onward. RESULTS: Flare-free survival was significantly higher at 36 months with RTX compared with MMF and CYC (100% for RTX vs. 83% for MMF. and 53% for CYC, p = 0·006). Twelve patients (76.5%) achieved complete remission with RTX compared with five (41.7%) and seven (46.7%) with MMF and CYC, respectively, at last follow-up. Requirement of mean daily dosage of prednisone was significantly lower in RTX group [p = 0.005 (RTX vs MMF); 0.0001 (RTX vs CYC) at 36 months] compared with other groups after the 3-month follow-up. In comparison with few minor adverse events in the other two cohorts, several serious adverse events occurred in the CYC group. CONCLUSIONS: Efficacy and medium-term safety of RTX induction followed by MMF maintenance therapy in inducing and maintaining remission among children with LN were evident in this study.

Efficacy and outcomes of continuous peritoneal dialysis versus daily intermittent hemodialysis in pediatric acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) requiring renal replacement therapy (RRT) is associated with high patient morbidity and mortality. There is no consensus on the best RRT modality for pediatric AKI. METHODS: The efficacy and safety of continuous peritoneal dialysis (cPD) and daily intermittent hemodialysis (dHD) were compared in 136 children aged 1 month to 16 years requiring RRT for AKI. Mortality, risk factors and causes of death, 1-month and 3-month renal recovery rates, and technique-related complications were assessed. RESULTS: Uremia control and the rate of catheter-related complications were comparable in the groups. Thirty-day survival was 60.7 % (51 out of 84) with cPD and 36.5 % (19 out of 52) with dHD (p = 0.019). Although age <1 year, extended time lag from disease onset to RRT initiation, mechanical ventilation, and extended vasopressor dependence independently predicted death, adjusted mortality was higher with dHD relative to cPD (hazard ratio [HR] 1.75, 95%CI 1.18-2.84, p = 0.022). Almost all fatalities in the dHD group (94 %) occurred during or within an hour of a HD session. Renal function normalized in 27 % of survivors after 4 weeks and in 51 % after 3 months. The risk of permanent end-stage renal disease was increased in patients with an intrinsic renal cause of AKI (HR 2.72; 95 % CI 1.37-3.83; p = 0.029) and in those with delayed RRT initiation (HR 2.17; 95 % CI 123-2.93; p = 0.015), but did not differ between patients treated with dHD and cPD. CONCLUSIONS: Favorable patient survival with cPD compared with dHD in children treated for AKI was evident in this study.

Congenital chylous ascites treated successfully with MCT-Based formula and octreotide.

Medium chain triglyceride (MCT)-based diet, total parenteral nutrition (TPN) and repeated paracentesis are considered as supportive management for congenital chylous ascites (CCA). TPN is considered where therapy with oral MCT is poorly tolerated by the patient especially young infant with unstable hemodynamic. Surgery is recommended when medical therapy fails. Herein, we report a 2½-month-old infant with CCA, treated successfully with octreotide intravenous infusion after the initial failure to response to conventional conservative therapy with MCT-enriched formula and paracentesis.

Tuberous sclerosis presenting with hemorrhagic stroke.

BACKGROUND: Incidence of intracerebral hemorrhage in patients with tuberous sclerosis is rare, and in most of the cases it is associated with either underlying cerebrovascular malformation or hemorrhage into the subependymal giant cell astrocytoma. CASE CHARACTERISTICS: A 2-year-old boy presented with a hemorrhagic stroke, and subsequently diagnosed as a case of tuberous sclerosis. OBSERVATION: Detailed work-up for stroke did not reveal any definite etiology. OUTCOME: Weakness gradually improved. Follow-up neuroimaging showed resolution of hemorrhage. MESSAGE: Clinician must be aware regarding this rare presentation of tuberous sclerosis.