Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome

Atypical hemolytic uremic syndrome (aHUS) is caused by alternative complement pathway dysregulation, leading to systemic thrombotic microangiopathy (TMA) and severe end-organ damage. Based on 2 prospective studies in mostly adults and retrospective data in children, eculizumab, a terminal complement inhibitor, is approved for aHUS treatment. Here we prospectively evaluated efficacy and safety of weight-based dosing of eculizumab in eligible pediatric patients with aHUS in an open-label phase II study. The primary end point was complete TMA response by 26 weeks. Twenty-two patients (aged 5 months-17 years) were treated; 16 were newly diagnosed, 12 had no prior plasma exchange/infusion during current TMA symptomatology, 11 received baseline dialysis, and 2 had prior renal transplants. By week 26, 14 achieved a complete TMA response, 18 achieved hematologic normalization, and 16 had 25% or better improvement in serum creatinine. Plasma exchange/infusion was discontinued in all, and 9 of the 11 patients who required dialysis at baseline discontinued, whereas none initiated new dialysis. Eculizumab was well tolerated; no deaths or meningococcal infections occurred. Bone marrow failure, wrist fracture, and acute respiratory failure were reported as unrelated severe adverse events. Thus, our findings establish the efficacy and safety of eculizumab for pediatric patients with aHUS and are consistent with proposed immediate eculizumab initiation following diagnosis in children

Pediatric Immunization Practices in Nephrotic Syndrome: An Assessment of Provider and Parental Knowledge

Background: Children with nephrotic syndrome (NS) are at high risk for vaccine-preventable infections due to the immunological effects from the disease and concurrent treatment with immunosuppressive medications. Immunizations in these patients may be deferred due to their immunosuppressive treatment which may increase the risk for vaccine-preventable infections. Immunization practices in children with NS continue to vary among pediatric nephrologists. This raises the question of whether children with NS are receiving the recommended vaccinations at appropriate times. Therefore, it is critical to understand the practices and patient education provided by physicians to patients on the topic of vaccinations. Methods: After informed consent, parents/guardians of 153 pediatric patients (\u3c18 years old) diagnosed with NS from 2005 to 2018 and 50 pediatric nephrologists from 11 participating centers completed anonymous surveys to evaluate immunization practices among pediatric nephrologists, assess the vaccine education provided to families of children with NS, assess the parental knowledge of immunization recommendations, and assess predictors of polysaccharide pneumococcal vaccine adherence. The Advisory Committee on Immunization Practices (ACIP) Immunization 2019 Guideline for those with altered immunocompetence was used to determine accuracy of vaccine knowledge and practices. Results: Forty-four percent of providers self-reported adherence to the ACIP guidelines for inactive vaccines and 22% to the guidelines for live vaccines. Thirty-two percent of parents/guardians reported knowledge that aligned with the ACIP guidelines for inactive vaccines and 1% for live vaccines. Subjects residing in the Midwest and provider recommendations for vaccines were positive predictors of vaccine adherence (p \u3c 0.001 and p 0.02, respectively). Conclusions: Vaccine recommendation by medical providers is paramount in vaccine adherence among pediatric patients with NS. This study identifies potential educational opportunities for medical subspecialty providers and family caregivers about immunization recommendations for immunosuppressed patients

COVID-19 in pediatric kidney transplantation: The Improving Renal Outcomes Collaborative.

There are limited data on the impact of COVID-19 in children with a kidney transplant (KT). We conducted a prospective cohort study through the Improving Renal Outcomes Collaborative (IROC) to collect clinical outcome data about COVID-19 in pediatric KT patients. Twenty-two IROC centers that care for 2732 patients submitted testing and outcomes data for 281 patients tested for SARS-CoV-2 by PCR. Testing indications included symptoms and/or potential exposures to COVID-19 (N = 134, 47.7%) and/or testing per hospital policy (N = 154, 54.8%). Overall, 24 (8.5%) patients tested positive, of which 15 (63%) were symptomatic. Of the COVID-19-positive patients, 16 were managed as outpatients, six received non-ICU inpatient care and two were admitted to the ICU. There were no episodes of respiratory failure, allograft loss, or death associated with COVID-19. To estimate incidence, subanalysis was performed for 13 centers that care for 1686 patients that submitted all negative and positive COVID-19 results. Of the 229 tested patients at these 13 centers, 10 (5 asymptomatic) patients tested positive, yielding an overall incidence of 0.6% and an incidence among tested patients of 4.4%. Pediatric KT patients in the United States had a low estimated incidence of COVID-19 disease and excellent short-term outcomes

Mycophenolate mofetil in children with steroid-dependent and/or frequently relapsing nephrotic syndrome.

Background: Mycophenolate mofetil (MMF) has emerged as a new agent for treatment of a variety of glomerular diseases. This study ex-amines the safety and efficacy of MMF in treating pediatric patients with steroid-dependent (SD) and/or frequently relapsing (FR) nephrotic syndrome (NS). Methods: We retrospectively reviewed the medical records of 18 pa-tients with SDNS and/or FRNS treated with MMF for at least 3 months. MMF was used in 11 patients with SDNS (n=10) and FRNS (n=1), includ-ing 7 males and 4 females. Results: Mean age at time of diagnosis of NS was 3.3 years (range, 1.1-8.5 years), and at the start of MMF 5.9 years (range, 2.9-10 years). Seven patients had a renal biopsy prior to starting MMF; all had me-sangial proliferative glomerulonephritis. Mean follow-up after starting MMF was 12.2 months (range, 4-24 months). Mean MMF dose was 948 mg/m2/day (range, 500-1087 mg/m2/day). MMF resulted in improvement in 9 of 11 patients, with 8 patients weaned off steroids completely, with a reduction in the mean relapse rate from 4.7 relapses/patient/year (range, 2.4-6) before MMF to 1.05 relapses/patient/year (range, 0-4.5) after MMF therapy (P=0.0001). The relative risk for relapse before MMF was 4.7 (P=0.0002). None of the patients had significant adverse events or intol-erance to MMF therapy. Conclusion: We conclude that MMF is a safe and effective option for treatment of children with SDNS and/or FRNS

A prospective study of paediatric patients with atypical haemolytic uraemic syndrom (aHUS) treated with eculuzumab : 1- year update

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Practice patterns and influence of allograft nephrectomy in pediatric kidney re- transplantation: A pediatric nephrology research consortium study

IntroductionThere are no guidelines regarding management of failed pediatric renal transplants.Materials & MethodsWe performed a first of its kind multicenter study assessing prevalence of transplant nephrectomy, patient characteristics, and outcomes in pediatric renal transplant recipients with graft failure from January 1, 2006, to December 31, 2016.ResultsFourteen centers contributed data on 186 pediatric recipients with failed transplants. The 76 recipients that underwent transplant nephrectomy were not significantly different from the 110 without nephrectomy in donor or recipient demographics. Fifty- three percent of graft nephrectomies were within a year of transplant. Graft tenderness prompted transplant nephrectomy in 91% (P < .001). Patients that underwent nephrectomy were more likely to have a prior diagnosis of rejection within 3 months (43% vs 29%; P = .04). Nephrectomy of allografts did not affect time to re- listing, donor source at re- transplant but significantly decreased time to (P = .009) and incidence (P = .0002) of complete cessation of immunosuppression post- graft failure. Following transplant nephrectomy, recipients were significantly more likely to have rejection after re- transplant (18% vs 7%; P = .03) and multiple rejections in first year after re- transplant (7% vs 1%; P = .03).ConclusionsPractices pertaining to failed renal allografts are inconsistent- 40% of failed pediatric renal allografts underwent nephrectomy. Graft tenderness frequently prompted transplant nephrectomy. There is no apparent benefit to graft nephrectomy related to sensitization; but timing / frequency of immunosuppression withdrawal is significantly different with slightly increased risk for rejection following re- transplant.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/169276/1/petr13974.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/169276/2/petr13974_am.pd

Adrenocorticotropic Hormone for Childhood Nephrotic Syndrome: The ATLANTIS Randomized Trial

Background and objectives There is renewed interest in adrenocorticotropic hormone (ACTH) for the treatment of nephrotic syndrome. We evaluated the efficacy and safety of ACTH in children with frequently relapsing or steroid-dependent nephrotic syndrome in a randomized trial. Design, setting, participants, & measurements Participants aged 2–20 years old with frequently relapsing or steroid-dependent nephrotic syndrome were enrolled from 16 sites in the United States and randomized 1:1 to ACTH (repository corticotropin injection) or no relapse-preventing treatment. ACTH treatment regimen was 80 U/1.73 m2 administered twice weekly for 6 months, followed by 40 U/1.73 m2 administered twice weekly for 6 months. The primary outcome was disease relapse during the first 6 months. Participants in the control group were offered crossover to ACTH treatment if they relapsed within 6 months. Secondary outcomes were relapse after ACTH dose reduction and treatment side effects. Results The trial was stopped at a preplanned interim analysis after enrollment of 31 participants because of a lack of discernible treatment efficacy. Fourteen out of 15 (93%) participants in the ACTH arm experienced disease relapse in the first 6 months, with a median time to first relapse of 23 days (interquartile range, 9–32), compared with 15 out of 16 (94%) participants and at a median of 21 days (interquartile range, 14–51) in the control group. There was no difference in the proportion of relapsed patients (odds ratio, 0.93; 95% confidence interval, 0.05 to 16.40; P>0.99) or time to first relapse (hazard ratio, 1.03; 95% confidence interval, 0.50 to 2.15; P=0.93). Thirteen out of 16 participants in the control group crossed over to ACTH treatment. Three out of 28 participants completed 12 months of ACTH treatment; the others exited the trial because of frequent relapses or side effects. There were no disease relapses after ACTH dose reduction among the three participants. Most side effects were mild and similar to side effects of corticosteroids. Conclusions ACTH at 80 U/1.73 m2 administered twice weekly was ineffective at preventing disease relapses in pediatric nephrotic syndrome