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.
To determine the lifetime prevalence of allergies in childhood nephrotic syndrome, the seasonality of presentation and relapses, and the impact of allergies on subsequent relapses.
In a longitudinal ...cohort of children with nephrotic syndrome (ages 1-18 years), assessment for allergic diseases was conducted using the validated and modified version of the International Study of Asthma and Allergies in Childhood questionnaire at enrollment. Outcomes included frequently relapsing nephrotic syndrome, relapse rates, and the relapse-free duration after initial steroid therapy.
Among 277 participants, the majority were male (65%) with a median age of 3.7 years (IQR 2.8-5.8) at presentation. A total of 64% reported lifetime allergies with 20% having asthma, 33% wheezing, 27% eczema, and 24% rhinitis. Over 3.3 years of follow-up, presence of asthma and allergies was not associated with frequently relapsing nephrotic syndrome (OR 1.20; 95% CI 0.60, 2.40), higher relapse rates (relative risk 0.95; 95% CI 0.71, 1.27), or risk of first relapse (hazard ratio 1.10; 95% CI 0.83, 1.47) compared with those with no history of allergic diseases. There was also no seasonal variation evident at initial presentation or frequency of relapses.
Two-thirds of children with nephrotic syndrome at presentation have allergic symptoms and asthma; however, neither are associated with an increased frequency of relapses.
BACKGROUND.Obesity is a significant public health concern; however, the incidence post solid-organ transplantation is not well reported.
METHODS.This study determined the incidence and risk factors ...of obesity among pediatric solid-organ transplant recipients (heart, lung, liver, kidney, multiorgan) at The Hospital for Sick Children (2002–2011), excluding prevalent obesity. Follow-up occurred from transplantation until development of obesity, last follow-up, or end of study. Incidence of obesity was determined overall, by baseline body mass index, and organ group. Risk factors were assessed using Cox proportional-hazards regression.
RESULTS.Among 410 (55% male) children, median transplant age was 8.9 (interquartile range IQR1.0-14.5) years. Median follow-up time was 3.6 (IQR1.5-6.4) years. Incidence of obesity was 65.2 (95% confidence interval CI52.7-80.4) per 1000 person-years. Overweight recipients had a higher incidence, 190.4 (95% CI114.8-315.8) per 1000 person-years, than nonoverweight recipients, 56.1 (95% CI44.3-71.1). Cumulative incidence of obesity 5-years posttransplant was 24.1%. Kidney relative to heart recipients had the highest risk (3.13 adjusted hazard ratio aHR; 95% CI1.53-6.40) for obesity. Lung and liver recipients had similar rates to heart recipients. Those with higher baseline body mass index (z-score; 1.72 aHR; 95% CI1.39-2.14), overweight status (2.63 HR; 95% CI1.71-4.04), and younger transplant age (y; 1.18 aHR; 95% CI1.12-1.25) were at highest risk of obesity. Higher cumulative steroid dosage (per 10 mg/kg) was associated with increased risk of obesity after adjustment.
CONCLUSIONS.Among all transplanted children at The Hospital for Sick Children, 25% developed obesity within 5-years posttransplant. Kidney recipients, younger children, those overweight at transplant, and those with higher cumulative steroid use (per 10 mg/kg) were at greatest risk. Early screening and intervention for obesity are important preventative strategies.
Background
Icodextrin is a solution of glucose polymers developed to provide sustained ultrafiltration over an extended dwell. Our aim was to determine whether or not fill volume with icodextrin ...contributes to the ability to achieve ultrafiltration in children.
Methods
The charts of all children on chronic peritoneal dialysis between January 2000 and July 2014 were screened for the use of an icodextrin day dwell. Data were extracted from the electronic chart and the HomeChoice™ Pro card and corrected for body surface area (BSA).
Results
Fifty children had an icodextrin day dwell. A linear correlation was found between the daytime fill volume and net ultrafiltration (
p
< 0.001). More ultrafiltration was achieved with a fill volume above 550 ml/m
2
BSA (107 ± 75 ml/m
2
BSA) than with smaller fill volumes (−8 ± 99 ml;
p
= 0.004). Ultrafiltration was achieved in 88 % of children with a fill volume above 550 ml/m
2
BSA versus only 44 % of patients with a smaller fill volume (
p
= 0.001). Icodextrin was well tolerated.
Conclusions
Our observations reveal that the larger the fill volume the higher the likelihood of achieving ultrafiltration with icodextrin and suggest that a minimum day dwell volume of 550 ml/m
2
BSA seems to facilitate ultrafiltration in children. To our knowledge this is the largest study addressing ultrafiltration with icodextrin in children.
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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Nephrotic syndrome is one of the most commonly diagnosed kidney diseases in childhood and its progressive forms can lead to chronic kidney disease (CKD) and/or end-stage renal disease (ESRD). There ...have been few longitudinal studies among a multi-ethnic cohort to determine potential risk factors influencing disease susceptibility, treatment response, and progression of nephrotic syndrome. Temporal relationships cannot be studied through cross-sectional study design. Understanding the interaction between various factors is critical to developing new strategies for treating children with kidney disease. We present the rationale and the study design of a longitudinal cohort study of children with nephrotic syndrome, the Insight into Nephrotic Syndrome: Investigating Genes, Health and Therapeutics (INSIGHT) study. The specific aims are to determine: 1) socio-demographic, environmental, and genetic factors that influence disease susceptibility; 2) rates of steroid treatment resistance and steroid treatment dependence, and identify factors that may modify treatment response; 3) clinical and genetic factors that influence disease susceptibility and progression to CKD and ESRD; and 4) the interaction between the course of illness and socio-demographic, environmental, and clinical risk factors.
INSIGHT is a disease-based observational longitudinal cohort study of children with nephrotic syndrome. At baseline, participants complete questionnaires and provide biological specimen samples (blood, urine, and toenail clippings). Follow-up questionnaires and repeat biological specimen collections are performed annually for up to five years.
The proposed cohort will provide the structure to test various risk factors predicting or influencing disease susceptibility, treatment response, and progression to CKD among children with nephrotic syndrome.
ClinicalTrials.gov Identifier NCT01605266.
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
Background
Children with nephrotic syndrome are at risk of obesity and growth impairment from repeated steroid treatment. However, incidence and risk factors for obesity and short stature remain ...uncertain, which is a barrier to preventative care. Our aim was to determine risk, timing, and predictors of obesity and short stature among children with nephrotic syndrome.
Methods
We evaluated obesity and longitudinal growth among children (1–18 years) enrolled in Insight into Nephrotic Syndrome: Investigating Genes, Health, and Therapeutics. We included children with nephrotic syndrome diagnosed between 1996–2019 from the Greater Toronto Area, Canada, excluding congenital or secondary nephrotic syndrome. Primary outcomes were obesity (body mass index Z-score ≥ + 2) and short stature (height Z-score ≤ -2). We evaluated prevalence of obesity and short stature at enrolment (< 1-year from diagnosis) and incidence during follow-up. Cox proportional hazards models determined the association between nephrotic syndrome classification and new-onset obesity and short stature.
Results
We included 531 children with nephrotic syndrome (30% frequently relapsing by 1-year). At enrolment, obesity prevalence was 23.5%, 51.8% were overweight, and 4.9% had short stature. Cumulative incidence of new-onset obesity and short stature over median 4.1-year follow-up was 17.7% and 3.3% respectively. Children with frequently relapsing or steroid dependent nephrotic syndrome within 1-year of diagnosis were at increased risk of new-onset short stature (unadjusted hazard ratio 3.99, 95%CI 1.26–12.62) but not obesity (adjusted hazard ratio 1.56, 95%CI 0.95–2.56). Children with ≥ 7 and ≥ 15 total relapses were more likely to develop obesity and short stature, respectively.
Conclusions
Obesity is common among children with nephrotic syndrome early after diagnosis. Although short stature was uncommon overall, children with frequently relapsing or steroid dependent disease are at increased risk of developing short stature. Effective relapse prevention may reduce steroid toxicity and the risk of developing obesity or short stature.
Graphical abstract
A higher resolution version of the Graphical abstract is available as
Supplementary information
Cardiovascular disease results in increased morbidity and mortality in pediatric kidney transplant recipients. Longitudinal changes in cardiac structure and function and the association with blood ...pressure control over time in pediatric kidney transplant recipients are unknown.
To determine the influence of blood pressure control on cardiac changes following pediatric kidney transplant, we conducted a retrospective cohort study of children who received their first kidney transplant at the Hospital for Sick Children from 2004 to 2015. Children were followed until transfer to adult care or censoring in July 2018. Cardiac structure and function parameters were collected from clinical echocardiograms and assessed using standardized scores. Blood pressure control was determined by systolic blood pressure
scores (above or below the 90th percentile) in combination with antihypertensive medications. A segmented mixed-effects model assessed
scores of interventricular septum thickness, left ventricular end-diastolic dimension, and left ventricular posterior wall dimension.
Of 142 children included, 58% were men, mean age at transplant was 11 (±4.5) years, and average follow-up time was 4 (±3) years. All cardiac structural
scores improved during follow-up. Interventricular septum thickness normalized at 4.0 years post-transplant. Left ventricular end-diastolic dimension normalized at 1.5 years post-transplant. Left ventricular posterior wall dimension normalized at 6.3 years post-transplant. Left ventricular mass index showed sustained improvement up to 12 years post-transplant. Individuals with uncontrolled blood pressure had increased left ventricular mass (β=2.97 95% CI, 0.77-5.16).
Cardiac structural abnormalities improve following kidney transplantation and normalize within 7 years, especially with controlled blood pressure. Strict blood pressure control is critical after pediatric kidney transplantation.
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