As life expectancy among pediatric solid organ transplant recipients (SOTRs) improves, the risk of comorbid conditions such as malignancy post-transplantation has also increased. SOTRs are at ...elevated risks of post-transplantation lymphoproliferative disorders (PTLDs), and skin and solid cancers. PTLDs typically occur early following transplantation, while skin and solid cancers frequently arise in young adulthood (25–40 years). By 30 years following transplantation, 26–41% of pediatric SOTRs have developed cancer. Different risk factors exist for PTLD, and skin and solid cancers, which are modified by cumulative immunosuppression, infections, transplanted organ, and the underlying disease process associated with initial organ failure (e.g., kidney failure). Optimal cancer treatment strategies depend on the specific cancer type, stage, and patient comorbidities. Immunosuppression reduction may be beneficial for certain cancers but must be considered against the risks of acute and chronic rejection and allograft loss. Lifestyle counseling regarding smoking avoidance and sun protection, as well as human papillomavirus vaccination, is an important aspect of cancer prevention. Currently, no cancer screening guidelines exist specifically for pediatric SOTRs. Adult population screening guidelines have not been validated in transplant populations. Therefore, an individualized approach should be taken to cancer screening for pediatric SOTRs, accounting for other cancer risk factors.
Hypertension is increasing in children and warrants disease surveillance. We therefore sought to evaluate the validity of case definitions to identify pediatric hypertension in administrative ...healthcare data. Cases of hypertension in children 3-18 years of age were identified utilizing blood pressures recorded in the Manitoba Primary Care Research Network (MaPCReN) electronic medical record from 2014 to 2016. Prevalence of hypertension and associated clinical characteristics were determined. We then evaluated the validity of 18 case definitions combining outpatient physician visits (ICD9CM codes), hospital claims (ICD9CM/ICD10 codes) and antihypertensive use within 1-3 years of data housed at the Manitoba Centre for Health Policy. The MaPCReN database identified 241 children with hypertension and 4090 without (prevalence = 5.6%). The sensitivity of algorithms ranged between 0.18 and 0.51 and the specificity between 0.98 and 1.00. Pharmaceutical use increased the sensitivity of algorithms significantly. The algorithms with the highest sensitivity and area under the ROC curve were 1 or more hospitalization OR 1 or more physician claim OR 1 or more pharmaceutical record. Evaluating 2 years of data is recommended. Administrative data alone reflects diagnosis of hypertension with high specificity, but underestimate the true prevalence of this disease. Alternative data sources are therefore required for disease surveillance.
Few studies have characterized follow-up after pediatric acute kidney injury (AKI). Our aim was to describe outpatient AKI follow-up after pediatric intensive care unit (PICU) admission.
Two-center ...retrospective cohort study (0-18 years; PICU survivors (2003-2005); noncardiac surgery; and no baseline kidney disease). Provincial administrative databases were used to determine outcomes.
AKI (KDIGO (Kidney Disease: Improving Global Outcomes) definitions).
post-discharge nephrology, family physician, pediatrician, and non-nephrology specialist visits. Regression was used to evaluate factors associated with the presence of nephrology follow-up (Cox) and the number of nephrology and family physician or pediatrician visits (Poisson), among AKI survivors.
Of n = 2041, 355 (17%) had any AKI; 64/355 (18%) had nephrology; 198 (56%) had family physician or pediatrician; and 338 (95%) had family physician, pediatrician, or non-nephrology specialist follow-up by 1 year post discharge. Only 44/142 (31%) stage 2-3 AKI patients had nephrology follow-up by 1 year. Inpatient nephrology consult (adjusted hazard ratio (aHR) 7.76 95% confidence interval (CI) 4.89-12.30), kidney admission diagnosis (aHR 4.26 2.21-8.18), and AKI non-recovery by discharge (aHR 2.65 1.55-4.55) were associated with 1-year nephrology follow-up among any AKI survivors.
Nephrology follow-up after AKI was uncommon, but nearly all AKI survivors had follow-up with non-nephrologist physicians. This suggests that AKI follow-up knowledge translation strategies for non-nephrology providers should be a priority.
Pediatric AKI survivors have high long-term rates of chronic kidney disease (CKD) and hypertension, justifying regular kidney health surveillance after AKI. However, there is limited pediatric data on follow-up after AKI, including the factors associated with nephrology referral and extent of non-nephrology follow-up. We found that only one-fifth of all AKI survivors and one-third of severe AKI (stage 2-3) survivors have nephrology follow-up within 1 year post discharge. However, 95% are seen by a family physician, pediatrician, or non-nephrology specialist within 1 year post discharge. This suggests that knowledge translation strategies for AKI follow-up should be targeted at non-nephrology healthcare providers.
Nephrotic syndrome is a common glomerular disease in children with significant variability in both incidence and steroid responsiveness among various ethnic groups. The average incidence of nephrotic ...syndrome is 2-16.9 per 100,000 children worldwide. Understanding the variability by ethnicity may point to potential factors leading to nephrotic syndrome, which remains elusive, and may highlight factors accounting for differences in medication response. The emerging role of genetic factors associated with steroid responsive and steroid-resistant forms of nephrotic syndrome within an ethnic group can provide insight into potential biological mechanisms leading to disease. For example, among African-Americans, the risk variants in APOL1 are associated with a more than 10-fold increase in risk of focal segmental glomerulosclerosis and high-risk carriers have a twofold greater risk of progression to end-stage renal disease. Ongoing collaborative studies should consider capturing data on self-reported ethnicity to understand differences in incidence and outcomes. In the future, the availability of whole-genome data will provide an excellent opportunity for new clinical and translational research in childhood nephrotic syndrome and lead to a better understanding of the disease.
Background
Children with antenatal hydronephrosis (ANH) diagnosed with postnatal asymptomatic vesicoureteral reflux (VUR) are thought to be at higher risk of urinary tract infection (UTI). As such, ...continuous antibiotic prophylaxis (CAP) is empirically recommended until age of toilet training; however, there are limited data to support this. The objective of this systematic review was to summarize the existing data and compare UTI rates in infants with asymptomatic VUR on CAP during the first year of life, to those not on CAP. Secondary objectives were to determine associated risk factors with UTI development.
Methods
A systematic search of all relevant studies and abstracts was conducted using 4 electronic databases by utilizing appropriate key words by an expert hospital librarian. Eligible studies included children with prenatal hydronephrosis, asymptomatic VUR with or without CAP, and reported on development of UTI in the first year.
Results
Of 6903 citations screened, 18 were selected, giving a total population of 829 (69.4% male, median age 57 days) who met the inclusion criteria. Most studies were retrospective and of low-quality evidence. Overall, 15.4% of patients developed at least one breakthrough UTI and females had a higher risk of UTI (odds ratio (OR) 2.3, 95% CI 1.1–4.7). Comparison with children not taking CAP was not readily reported, and meta-analysis could not be completed.
Conclusions
Randomized controlled trials and standardized reporting of clinical variables are required to understand the protective effect of antibiotic prophylaxis in this cohort.
Background
There are similarities in hemodialysis (HD) between adults and children and also unique pediatric aspects. In this systematic review, we evaluated the existing HD literature, including ...vascular access, indications, parameters, and outcomes as a reflection on real-life HD practices.
Methods
Medline, Embase, CINAHL, Web of Science, and Cochrane Library were systematically searched for literature on HD in children (1–20 years). Two reviewers independently assessed the literature and data on indications; vascular access, outcomes, and specific parameters for HD were extracted.
Results
Fifty-four studies (8751 patients) were included in this review. Studies were stratified into age groups 1–5, 6–12, and 13–20 years based on median/mean age reported in the study, as well as era of publication (1990–2000, 2001–2010, and 2011–2019). Across all age groups, both arteriovenous fistulas and central venous catheters were utilized for vascular access. Congenital abnormalities and glomerulopathy were the most common HD indications. HD parameters including HD session duration, dialysate and blood flow rates, urea reduction ratio, and ultrafiltration were characterized for each age group, as well as common complications including catheter dysfunction and intradialytic hypotension. Median mortality rates were 23.3% (3.3), 7.6% (14.5), and 2.0% (3.0) in ages 1–5, 6–12, and 13–20 years, respectively. Median transplantation rates were 41.6% (38.3), 52.0% (32.0), and 21% (25.6) in ages 1–5, 6–12, and 13–20, respectively.
Conclusion
This comprehensive systematic review summarizes available literature on HD in children and young adults, including best vascular access, indications, technical aspects, and outcomes, and reflects on HD practices over the last three decades.
Kawasaki disease (KD) incidence is increasing in Ontario. Cardiovascular sequelae following KD are well-described. However, there are limited data on non-cardiovascular outcomes.
To determine the ...risk of hearing loss, anxiety, developmental disorders, intellectual disabilities and attention-deficit/hyperactivity disorder (ADHD) among KD survivors vs. non-exposed children.
We included all Ontario children (≤18 yr) surviving hospitalization with a KD diagnosis between 1995 and 2018, using population-based health administrative databases. We excluded children with prior KD diagnoses and non-residents. KD cases were matched with 100 non-exposed children by age, sex and year. Follow-up continued until death or March 2019. We calculated the prevalence, incidence and adjusted hazard ratios (aHR 95%CI) of outcomes between 0–1 yr, 1–5 yr, 5–10 yr and >10 yr follow-up.
Among 4597 KD survivors, 364 (7.9%) were diagnosed with hearing loss, 1213 (26.4%) anxiety disorders, 398 (8.7%) developmental disorders, 51 (1.1%) intellectual disability and 21 (0.5%) ADHD, during median 11 year follow-up. Compared to 459,700 non-exposed children, KD survivors were not at increased risk of hearing loss after adjustment for potential confounders. KD survivors were at increased risk of anxiety disorders between 0–1 yr (aHR 1.75 1.46–2.10), 1–5 yr (aHR 1.13 1.01–1.28), 5–10 yr (aHR 1.14 1.03–1.28) and >10 yr (aHR 1.11 1.02–1.22); developmental disorders between 0–1 yr (aHR 1.49 1.28–1.74) and 1–5 yr (aHR 1.19 1.02–1.40); intellectual disabilities >10 yr (aHR 2.36 1.36–4.10); and ADHD >10 yr (aHR 2.01 1.14–3.57).
KD survivors are at increased risk of being diagnosed with anxiety disorders sooner, being diagnosed with developmental disorders between 0 and 5 yr and being diagnosed with intellectual disabilities or ADHD >10 yr after KD diagnosis. This may justify enhanced developmental and audiological surveillance of KD survivors.
Kawasaki disease (KD) is a childhood vasculitis with conflicting reported North American trends in incidence and patient characteristics.
(1) determine KD incidence between 1995 and 2017; (2) compare ...patient characteristics by era and age group; (3) determine complication and cardiovascular follow-up rates.
We used population-based health administrative data to identify children (0-18 yr) hospitalized with KD in Ontario, Canada between 1995 and 2017. We excluded children with prior KD diagnosis or incomplete records. We determined the annualized incidence and follow-up trends.
KD was diagnosed in 4,346 children between 1995 and 2017. Annual KD incidence was 22.0 (<5 yr), 6.1 (5-9 yr), and 0.6 (10-18 yr) per 100,000 children. KD incidence increased significantly for all age groups, including from 18.4 to 25.0 cases per 100,000 children <5 yr. Ninety-day mortality occurred in ≤5 children (≤0.1%). Coronary artery aneurysm (CAA) occurred in 106 children (2.4%, 95% confidence interval 2.0-2.9) during admission and 151 (3.5%, 95% confidence interval 3.0-4.1) during 11-year median follow-up. Children 10-18 yr had longer hospitalizations (4.3 vs. 3.5 days, p = 0.003) and more CAA (7.4% vs. 3.4%, p = 0.007). By 1-year post-diagnosis, 3970 (91.3%) and 2576 (59.3%) children had echocardiography and cardiology follow-up, respectively.
KD incidence is increasing in Ontario, with greater healthcare utilization from hospitalizations and subsequent follow-up.
4346 children were hospitalized for Kawasaki disease over 22 years in Ontario, and Kawasaki disease incidence increased significantly for all age groups, males and females. Older children (10-18 years) had longer hospital length of stay, more PICU admissions and more frequent coronary artery aneurysms. Nearly all children with Kawasaki disease had follow-up echocardiography within 1 year.
Bartter syndrome subtypes are a group of rare renal tubular diseases characterized by impaired salt reabsorption in the tubule, specifically the thick ascending limb of Henle's loop. Clinically, they ...are characterized by the association of hypokalemic metabolic alkalosis, hypercalciuria, nephrocalcinosis, increased levels of plasma renin and aldosterone, low blood pressure and vascular resistance to angiotensin II. Bartter syndrome type II is caused by mutations in the renal outer medullary potassium channel (ROMK) gene (KCNJ1), can present in the newborn period and typically requires lifelong therapy.
We describe a case of a prematurely born female infant presenting with antenatal polyhydramnios, and postnatal dehydration and hyponatremia. After 7 weeks of sodium supplementation, the patient demonstrated complete resolution of her hyponatremia and developed only transient metabolic alkalosis at 2 months of age but continues to be polyuric and exhibits hypercalciuria, without development of nephrocalcinosis. She was found to have two pathogenic variants in the KCNJ1 gene: a frameshift deletion, p.Glu334Glyfs*35 and a missense variant, p. Pro110Leu. While many features of classic ROMK mutations have resolved, the child does have Bartter syndrome type II and needs prolonged pediatric nephrology follow-up.
Transient neonatal hyponatremia warrants a multi-system workup and genetic variants of KCNJ1 should be considered.
Background
Post-infectious glomerulonephritis (PIGN) usually follows a benign course, but few children have an atypical, severe presentation, and these exceptional cases have been linked to the ...dysregulation of the complement alternative pathway (CAP). There is a considerable overlap in the histopathological features of PIGN and C3 glomerulopathy (C3G), which is also associated with CAP dysregulation but has a poorer outcome. We hypothesized that PIGN and C3G define a disease spectrum, and that in the past there may be some children with C3G who were misclassified with PIGN before C3G was described as a separate disease entity.
Methods
Children with PIGN (
n
= 33) diagnosed between 1985 and 2010 who underwent a renal biopsy due to their unusual course were reviewed and of them, 8 were reclassified into C3G based on the current classification criteria. Outcome was based on the degree of proteinuria, C3 level, and renal function at follow-up.
Results
Sixteen (72.7%) children with typical PIGN recovered completely as compared to only 2 (25%) with C3G. Of note, children with “typical” PIGN had a more severe disease course at onset; however, the outcome at last follow up was favorable.
Conclusions
Our results support the hypothesis that PIGN and C3G form a disease spectrum and have different long-term clinical implications and management strategies.
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