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 m 2 administered twice weekly for 6 months, followed by 40 U/1.73 m 2 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. ResultsThe 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 m 2 administered twice weekly was ineffective at preventing disease relapses in pediatric nephrotic syndrome.

Background/Aims: There is a critical need for more noninvasive biomarkers to identify nephritis in patients with systemic lupus erythematosus (SLE). Recent studies in a model mouse and an adult SLE patient cohort suggest that anti-basement membrane antibody levels correlate well with lupus activity and kidney injury. The purpose of this study was to assess the anti-basement membrane reactivity in pediatric SLE (pSLE) patients with or without nephritis. Methods: Auto-antibodies to basement membrane antigens were assessed using an anti-matrigel ELISA. Endpoint titers were measured in pSLE patients and healthy children, as well as in autoimmune and non-immune mice, with good reproducing capabilities. Findings were also analyzed with respect to the presence or absence of nephritis, dsDNA antibodies, and other manifestations of pSLE. Results: MRL/lpr mice developed high-titer anti-matrigel antibodies, whereas C57BL/6 mice did not. In a cohort of 21 pSLE patients and 22 pediatric controls, high-titer anti-matrigel IgG, IgM and IgA antibody levels were specific for pSLE. High-titer anti-matrigel IgG3 levels could distinguish with good sensitivity the 13 pSLE patients with a history of nephritis from the 8 non-renal pSLE patients. High-titer anti-matrigel IgG, IgA, IgM or IgG3 did not correlate with positive anti-double stranded DNA, but defined an overlapping subset of patients. Conclusion: The addition of anti-basement membrane antibody testing to serologic testing in pSLE may help to monitor disease activity or to define important subsets of patients with risks for specific disease manifestations.

Objective We studied the rate of remission of lupus nephritis (LN) in an international cohort of 248 children and adolescents with biopsy proven LN. Five different definitions from scientific studies and the definitions recommended by the American College of Rheumatology and Kidney Disease Improving Global Outcomes (KDIGO) were used. Methods Anonymized clinical data in patients with biopsy proven LN class ≥ III (International Society of nephrology/Royal Pathology Society-ISN/RPS) diagnosed and treated in the last 10 years in 23 international centers from 10 countries were collected. We compared the rate of patients in complete and partial remission applying the different definitions. Results The mean age at diagnosis was 11 years and 4 month and 177 were females. The number of patients in complete and partial remission varied a lot between the different definitions. At 24 months, between 50% and 78.8% of the patients were in full remission as defined by the different criteria. The number of patients in partial remission was low, between 2.3% and 25%. No difference in achieved remission was found between boys and girls or between children and adolescents (P > 0.05). Patients with East Asian ethnicity reached remission more often than other ethnicities (P = 0.03-0.0008). Patients treated in high income countries showed a higher percentage of complete remission at 12 and 24 months (P = 0.002-0.000001). Conclusion The rate of children and adolescents with LN achieving remission varied hugely with the definition used. Our results give important information for long awaited treatment studies in children and young people.

reported CNS-depressant effects. 8 Two opioids prescribed less frequently, fentanyl (6%) and methadone (4%), are among the safest opioids for patients with ESRD as they have no active metabolites and require no dose adjustments in HD. 7,8 Two patients (4%) were prescribed codeine-acetaminophen despite reported respiratory depression and narcolepsy from codeine use in kidney failure. 8 Our findings may not be generalizable to all HD patients given the small sample size from one location. Our method of determining duration of opioid therapy may over-or underestimate the true prevalence of both chronic pain and long-term opioid use in outpatient HD. Also, we did not ask patients directly about their pain, and those treated with nonopioid interventions like nonsteroidal anti-inflammatory drugs, gabapentin, transcutaneous electrical nerve stimulation units, or nerve blocks were not flagged for our review.We propose that any prescriber of opioids for HD patients reassess pain regularly and maintain a Pain Contract with the patient. Specifically, the source of pain and medication being prescribed should be documented. Reviewing available controlledsubstance databases periodically will help control for polypharmacy. We advocate selecting one provider who can best manage the HD patient's painful condition to minimize the risk for adverse events from multiple concurrent opioid prescriptions. With these measures, we aim to increase accountability and awareness when treating chronic pain in this population.

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Childhood-onset systemic lupus erythematosus (cSLE) only represents 20% of all SLE patients, and males with SLE only represent 10%. To study this rare SLE subset, males diagnosed with cSLE over a 30-year period were identified. Organ involvement, autoantibody production, hypocomplementemia, and kidney biopsy findings were compared to cSLE females. Outcomes were assessed using SLE Disease Activity Index scores, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, and Childhood Arthritis and Rheumatology Research Alliance definitions for nephritis responsiveness. Of 95 males and 545 females with cSLE, 62% and 57% developed nephritis, respectively. Median age of cSLE onset was 14 years in both genders. Among males, 80% of non-Hispanic whites, 64% of blacks, 59% of Hispanics, and 50% of Asians developed nephritis. The prevalence of pure and mixed class V membranous nephritis was 33%. Median follow-up was 3.2 years (range 0.1–18). Complete kidney responses were seen in 70% after a median 24 months; however, relapse rates were 46%. Kidney disease flares were 56% nephritic and 44% proteinuric. Males and females with cSLE present with comparable rates and nephritis class. While overall and kidney response rates are favorable, kidney disease relapses are common among males.

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