This letter to the editor discusses the use of eculizumab in refractory membranoproliferative glomerulonephritis. The response appears to be dramatic.
To the Editor:
Membranoproliferative ...glomerulonephritis (MPGN) mainly affects children, often progresses to end-stage kidney disease, and can recur after transplantation.
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Primary MPGN is one of several glomerulopathies that have recently been linked to dysregulation of the complement alternative pathway,
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which triggers the cytotoxic terminal complement response. Current therapeutic strategies for reestablishing complement regulation and preventing the effects of an overactive terminal complement cascade include plasma infusion and exchange and terminal complement blockade through the anti-C5 monoclonal antibody eculizumab.
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We describe a patient with refractory MPGN who had a dramatic response to eculizumab treatment.
A 16-year-old girl presented with . . .
BACKGROUND
Middle aortic syndrome (MAS) is a rare clinical entity in childhood, characterized by a severe narrowing of the distal thoracic and/or abdominal aorta, and associated with significant ...morbidity and mortality. MAS remains a relatively poorly defined disease. This paper systematically reviews the current knowledge on MAS with respect to etiology, clinical impact, and therapeutic options.
METHODS
A systematic search of 3 databases (Embase, MEDLINE, and Cochrane Central Register of Controlled Trials) yielded 1,252 abstracts that were screened based on eligibility criteria resulting in 184 full-text articles with 630 reported cases of childhood MAS. Data extracted included patient characteristics, clinical presentation, vascular phenotype, management, and outcomes.
RESULTS
Most cases of MAS are idiopathic (64%), 15% are associated with Mendelian disorders, and 17% are related to inflammatory diseases. Extra-aortic involvement including renal (70%), superior mesenteric (30%), and celiac (22%) arteries is common, especially among those with associated Mendelian disorders. Inferior mesenteric artery involvement is almost never reported. The majority of cases (72%) undergo endovascular or surgical management with residual hypertension reported in 34% of cases, requiring medication or reintervention. Clinical manifestations and extent of extra-aortic involvement are lacking.
CONCLUSIONS
MAS presents with significant involvement of visceral arteries with over two thirds of cases having renal artery stenosis, and one third with superior mesenteric artery stenosis. The extent of disease is worse among those with genetic and inflammatory conditions. Further studies are needed to better understand etiology, long-term effectiveness of treatment, and to determine the optimal management of this potentially devastating condition.
Ethnic differences in outcomes among children with nephrotic syndrome are unknown.
We conducted a longitudinal study at a single regional pediatric center comparing ethnic differences in incidence ...from 2001 to 2011 census data and longitudinal outcomes, including relapse rates, time to first relapse, frequently relapsing disease, and use of cyclophosphamide. Among 711 children, 24% were European, 33% were South Asian, 10% were East/Southeast Asian, and 33% were of other origins.
Over 10 years, the overall incidence increased from 1.99/100,000 to 4.71/100,000 among children ages 1-18 years old. In 2011, South Asians had a higher incidence rate ratio of 6.61 (95% confidence interval, 3.16 to 15.1) compared with Europeans. East/Southeast Asians had a similar incidence rate ratio (0.76; 95% confidence interval, 0.13 to 2.94) to Europeans. We determined outcomes in 455 children from the three largest ethnic groups with steroid-sensitive disease over a median of 4 years. South Asian and East/Southeast Asian children had significantly lower odds of frequently relapsing disease at 12 months (South Asian: adjusted odds ratio; 0.55; 95% confidence interval, 0.39 to 0.77; East/Southeast Asian: adjusted odds ratio; 0.42; 95% confidence interval, 0.34 to 0.51), fewer subsequent relapses (South Asian: adjusted odds ratio; 0.64; 95% confidence interval, 0.50 to 0.81; East/Southeast Asian: adjusted odds ratio; 0.47; 95% confidence interval, 0.24 to 0.91), lower risk of a first relapse (South Asian: adjusted hazard ratio, 0.74; 95% confidence interval, 0.67 to 0.83; East/Southeast Asian: adjusted hazard ratio, 0.65; 95% CI, 0.63 to 0.68), and lower use of cyclophosphamide (South Asian: adjusted hazard ratio, 0.82; 95% confidence interval, 0.53 to 1.28; East/Southeast Asian: adjusted hazard ratio, 0.54; 95% confidence interval, 0.41 to 0.71) compared with European children.
Despite the higher incidence among South Asians, South and East/Southeast Asian children have significantly less complicated clinical outcomes compared with Europeans.
Background
Steroids and/or steroid-sparing medications are commonly used for nephrotic syndrome treatment; however, the impact of these medications on health-related quality of life over time is not ...well described.
Methods
Longitudinal cohort is up to 5 years where children were assessed with baseline and annual Pediatric Quality of Life Inventory questionnaire. A mixed-effects linear regression determined differences in scores among children receiving steroids and/or steroid-sparing agents for at least 30 days compared with those not on medication at 1, 3, 6, and 12 months prior to assessment.
Results
Among 295 children, 64% were male, with a median age of 3.7 (interquartile range IQR, 2.7, 5.9) years at diagnosis, and comprised 25% Europeans, 40% South Asians, and 8% East/Southeast Asians. Adjusted HRQOL scores were reduced among children taking steroids and steroid-sparing agents among 705 HRQOL measures (median 2 IQR, 1, 3 per child). Compared to children without medication, steroid and steroid-sparing agent use up to 12 months prior to assessment were associated with an overall HRQOL drop of 3.17 (95% confidence interval CI, − 5.25, − 1.08) and 3.18 (95% CI, − 5.24, − 1.12), respectively, after adjustment. Functioning domain scores were reduced by 4.41 points (95% CI, − 6.57, − 2.25) in children on steroids, whereas fatigue domain scores were reduced by 5.47 points (95% CI, − 9.28, − 1.67) in children on steroid-sparing agents after adjustment.
Conclusions
HRQOL is consistently decreased in children receiving steroids and steroid-sparing agents, with differential effects on functioning and fatigue. Counseling families on possible effects of prolonged treatment periods is important in the management of childhood nephrotic syndrome.
It is unknown whether steroid sensitivity and other putative risk factors collected at baseline can predict the disease course of idiopathic nephrotic syndrome in childhood. We determined whether ...demographic, clinical, and family reported factors at presentation can predict outcomes in idiopathic nephrotic syndrome.
An observational cohort of 631 children aged 1 to 18 years diagnosed with idiopathic nephrotic syndrome between 1993 and 2016 were followed up until clinic discharge, 18 years of age, end-stage kidney disease (ESKD), or the last clinic visit. Baseline characteristics were age, sex, ethnicity, and initial steroid sensitivity. Of these, 287 (38%) children also reported any family history of kidney disease, preceding infection, microscopic hematuria, and history of asthma/allergies. The outcomes were complete remission after initial steroid course, need for a second-line agent, frequently relapsing disease, and long-term remission. The discriminatory power of the models was described using the c-statistic.
Overall, 25.7% of children had no further disease after their initial steroid course. In addition, 31.2% developed frequently relapsing disease; however, 77.7% were disease-free at 18 years of age. Furthermore, 1% of children progressed to ESKD. Logistic regression modeling using the different baseline exposures did not significantly improve the prediction of outcomes relative to the observed frequencies (maximum c-statistic, 0.63; 95% confidence interval CI, 0.59–0.67). The addition of steroid sensitivity did not improve outcome prediction of long-term outcomes (c-statistic, 0.63; 95% CI, 0.54–0.70).
Demographic, clinical, and family reported characteristics, specifically steroid sensitivity, are not useful in predicting relapse rates or long-term remission in idiopathic nephrotic syndrome. Further studies are needed to address factors that contribute to long-term health.
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Background:
Studies in the USA report differences in opinion among parents of different ethnic groups toward genetic testing for their child; however, there are no studies that address this issue in ...the diverse ethnic and immigrant population in Canada.
Objective:
This study aims to determine whether ethnicity and immigration status influences parental interest in clinical genetic testing for a potentially progressive kidney disease.
Design:
This is a cross-sectional study.
Setting:
Participants were recruited from the Greater Toronto Area, Canada.
Participants:
The study included 320 parents of children ages 1–18 years with nephrotic syndrome enrolled in the Insight into Nephrotic Syndrome: Investigating Genes, Health and Therapeutics (INSIGHT) observational cohort study.
Measurements:
Demographic, ethnicity, immigration, and child specific factors as well as interest in genetic testing were collected through self-reported questionnaires administered at baseline study visit.
Methods:
Logistic regression models were used to examine association of ethnicity and immigration status with interest in genetic testing.
Results:
The majority of parents (85 %) were interested in genetic testing for their child. South Asian and East/Southeast Asian parents had 74 and 76 % lower odds of agreeing to genetic testing when compared to Europeans (odds ratio (OR) 0.26, 95 % confidence interval (CI) 0.10–0.68; OR 0.24, 95 % CI 0.07–0.79, respectively) after controlling for age and sex of child, age and education level of parent, initial steroid resistance, and duration of time in Canada. Immigrants to Canada also had significantly lower odds (OR 0.29, 95 % CI 0.12–0.72) of agreeing to genetic testing after similar adjustment. Higher education level was not associated with greater interest in genetic testing (OR 1.24, 95 % CI 0.64–2.42).
Limitations:
Participants have already agreed to aggregate genetic testing for research purposes as part of enrolment in INSIGHT study.
Conclusion:
While majority of parents were interested in genetic testing for their child, immigrants, particularly South Asians and East/Southeast Asians, were more likely to decline genetic testing. Genetic counseling needs to be tailored to address specific concerns in these parental groups to maximize informed decision-making in the clinical setting.
Trial registration:
ClinicalTrials.gov, NCT01605266
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