Impact of childhood nephrotic syndrome on obesity and growth: a prospective cohort study.

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.

Long-term Health Care Utilization and Associated Costs After Dialysis-Treated Acute Kidney Injury in Children.

RATIONALE & OBJECTIVE: Acute kidney injury (AKI) is common among hospitalized children and is associated with increased hospital length of stay and costs. However, there are limited data on postdischarge health care utilization after AKI hospitalization. Our objectives were to evaluate health care utilization and physician follow-up patterns after dialysis-treated AKI in a pediatric population. STUDY DESIGN: Retrospective cohort study, using provincial health administrative databases. SETTING & PARTICIPANTS: All children (0-18 years) hospitalized between 1996 and 2017 in Ontario, Canada. Excluded individuals comprised non-Ontario residents; those with metabolic disorders or poisoning; and those who received dialysis or kidney transplant before admission, a kidney transplant by 104 days after discharge, or were receiving dialysis 76-104 days from dialysis start date. EXPOSURE: Episodes of dialysis-treated AKI, identified using validated health administrative codes. AKI survivors were matched to 4 hospitalized controls without dialysis-treated AKI by age, sex, and admission year. OUTCOME: Our primary outcome was postdischarge hospitalizations, emergency department visits, and outpatient physician visits. Secondary outcomes included outpatient visits by physician type and composite health care costs. ANALYTICAL APPROACH: Proportions with≥1 event and rates (per 1,000 person-years). Total and median composite health care costs. Adjusted rate ratios using negative binomial regression models. RESULTS: We included 1,688 pediatric dialysis-treated AKI survivors and 6,752 matched controls. Dialysis-treated AKI survivors had higher rehospitalization and emergency department visit rates during the analyzed follow-up periods (0-1, 0-5, and 0-10 years postdischarge, and throughout follow-up), and higher outpatient visit rates in the 0-1-year follow-up period. The overall adjusted rate ratio for rehospitalization was 1.46 (95% CI, 1.25-1.69; P<0.0001) and for outpatient visits was 1.16 (95% CI, 1.09-1.23; P=0.01). Dialysis-treated AKI survivors also had higher health care costs. Nephrologist follow-up was infrequent among dialysis-treated AKI survivors (18.6% by 1 year postdischarge). LIMITATIONS: Potential miscoding of study exposures or outcomes. Residual uncontrolled confounding. Data for health care costs and emergency department visits was unavailable before 2006 and 2001, respectively. CONCLUSIONS: Dialysis-treated AKI survivors had greater postdischarge health care utilization and costs versus hospitalized controls. Strategies are needed to improve follow-up care for children after dialysis-treated AKI to prevent long-term complications.

Cardiovascular outcomes in children with Kawasaki disease: a population-based cohort study.

BACKGROUND: The risk of cardiovascular events after Kawasaki disease (KD) remains uncertain. Our objective was to determine the risk of cardiovascular events and mortality after KD. METHODS: Population-based retrospective cohort study using Ontario health administrative databases (0-18 years; 1995-2018). EXPOSURE: pediatric KD hospitalizations. Each case was matched to 100 non-exposed controls. PRIMARY OUTCOME: major adverse cardiac events (MACE; cardiovascular death, myocardial infarction, or stroke composite). SECONDARY OUTCOMES: composite cardiovascular events and mortality. We determined incidence rates and adjusted hazard ratios (aHR) using multivariable Cox models. RESULTS: Among 4597 KD survivors, 79 (1.7%) experienced MACE, 632 (13.8%) composite cardiovascular events, and 9 (0.2%) died during 11-year median follow-up. The most frequent cardiovascular events among KD survivors were ischemic heart disease (4.6 events/1000 person-years) and arrhythmias (4.5/1000 person-years). KD survivors were at increased risk of MACE between 0-1 and 5-10 years, and composite cardiovascular events at all time periods post-discharge. KD survivors had a lower mortality risk throughout follow-up (aHR 0.36, 95% CI 0.19-0.70). CONCLUSION: KD survivors are at increased risk of post-discharge cardiovascular events but have a lower risk of death, which justifies enhanced cardiovascular disease surveillance in these patients. IMPACT: Among 4597 Kawasaki disease (KD) survivors, 79 (1.7%) experienced major adverse cardiac events (MACE) and 632 (13.8%) had composite cardiovascular events during 11-year median follow-up. KD survivors had significantly higher risks of post-discharge MACE and cardiovascular events versus non-exposed children. Only nine KD survivors (0.2%) died during follow-up, and the risk of mortality was significantly lower among KD survivors versus non-exposed children. Childhood KD survivors should receive preventative counseling and cardiovascular surveillance, aiming to mitigate adult cardiovascular disease.

Cardiovascular Outcomes During Index Hospitalization in Children with Kawasaki Disease in Ontario, Canada.

Kawasaki disease (KD) is a common childhood vasculitis associated with coronary artery aneurysms (CAA). However, there is limited published data on other cardiovascular events diagnosed during acute KD hospitalizations. Our objectives were to determine the incidence of cardiovascular events during acute KD hospitalizations, stratified by age at admission, CAA status, and pediatric intensive care unit (PICU) admission status. We identified all children (0-18 year) hospitalized with a new KD diagnosis in Ontario, between 1995 and 2018, through validated algorithms using population health administrative databases. We excluded children previously diagnosed with KD and non-Ontario residents. We evaluated for cardiovascular events that occurred during the acute KD hospitalizations, defined by administrative coding. Among 4597 children hospitalized with KD, 3307 (71.9%) were aged 0-4 years, median length of stay was 3 days (IQR 2-4), 113 children (2.5%) had PICU admissions, and 119 (2.6%) were diagnosed with CAA. During acute hospitalization, 75 children were diagnosed with myocarditis or pericarditis (1.6%), 47 with arrhythmias (1.0%), 25 with heart failure (0.5%), and ≤ 5 with acute MI (≤ 0.1%). Seven children underwent cardiovascular procedures (0.2%). Older children (10-18 years), children with CAA, and children admitted to the PICU were more likely to experience cardiovascular events, compared with children aged 0-4 years, without CAA or non-PICU admissions, respectively. The frequency of non-CAA cardiovascular events during acute KD hospitalizations did not change significantly between 1995 and 2018. During acute KD hospitalizations, older children, children with CAA, and PICU admissions are at higher risk of cardiovascular complications, justifying closer monitoring of these high-risk individuals.

Incidence of chronic immune-mediated inflammatory diseases after diagnosis with Kawasaki disease: a population-based cohort study.

OBJECTIVES: Kawasaki disease (KD) is an immune-mediated vasculitis of childhood with multi-organ inflammation. We determined the risk of subsequent immune-mediated inflammatory disease (IMID), including arthritis, type 1 diabetes, IBD, autoimmune liver disease, primary sclerosing cholangitis and multiple sclerosis. METHODS: We conducted a matched population-based cohort study using health administrative data from Ontario, Canada. Children aged <18 years born between 1991 and 2016 diagnosed with KD (n = 3753) were matched to 5 non-KD controls from the general population (n = 18 749). We determined the incidence of IMIDs after resolution of KD. Three- and 12-month washout periods were used to exclude KD-related symptoms. RESULTS: There was an elevated risk of arthritis in KD patients compared with non-KD controls, starting 3 months after index date [103.0 vs 12.7 per 100 000 person-years (PYs); incidence rate ratio 8.07 (95% CI 4.95, 13.2); hazard ratio 8.08 (95% CI 4.95, 13.2), resulting in the overall incidence of IMIDs being elevated in KD patients (175.1 vs 68.0 per 100 000 PYs; incidence rate ratio 2.58 (95% CI 1.93, 3.43); hazard ratio 2.58, 95% CI 1.94, 3.43]. However, there was no increased risk for diabetes, IBD, autoimmune liver disease, primary sclerosing cholangitis or multiple sclerosis in KD patients. Similar results were observed using a 12-month washout period. CONCLUSION: Children diagnosed with KD were at increased risk of arthritis following the acute KD event, but not other IMIDs. Health-care providers should monitor for arthritis in children following a diagnosis of KD.

Acute kidney injury in the pediatric intensive care unit: outpatient follow-up.

BACKGROUND: 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. METHODS: 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. EXPOSURE: AKI (KDIGO (Kidney Disease: Improving Global Outcomes) definitions). OUTCOMES: 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. RESULTS: 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. CONCLUSIONS: 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. IMPACT: 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.

Long-Term Kidney Outcomes Following Dialysis-Treated Childhood Acute Kidney Injury: A Population-Based Cohort Study.

BACKGROUND: AKI is common during pediatric hospitalizations and associated with adverse short-term outcomes. However, long-term outcomes among survivors of pediatric AKI who received dialysis remain uncertain. METHODS: To determine the long-term risk of kidney failure (defined as receipt of chronic dialysis or kidney transplant) or death over a 22-year period for pediatric survivors of dialysis-treated AKI, we used province-wide health administrative databases to perform a retrospective cohort study of all neonates and children (aged 0-18 years) hospitalized in Ontario, Canada, from April 1, 1996, to March 31, 2017, who survived a dialysis-treated AKI episode. Each AKI survivor was matched to four hospitalized pediatric comparators without dialysis-treated AKI, on the basis of age, sex, and admission year. We reported the incidence of each outcome and performed Cox proportional hazards regression analyses, adjusting for relevant covariates. RESULTS: We identified 1688 pediatric dialysis-treated AKI survivors (median age 5 years) and 6752 matched comparators. Among AKI survivors, 53.7% underwent mechanical ventilation and 33.6% had cardiac surgery. During a median 9.6-year follow-up, AKI survivors were at significantly increased risk of a composite outcome of kidney failure or death versus comparators. Death occurred in 113 (6.7%) AKI survivors, 44 (2.6%) developed kidney failure, 174 (12.1%) developed hypertension, 213 (13.1%) developed CKD, and 237 (14.0%) had subsequent AKI. AKI survivors had significantly higher risks of developing CKD and hypertension versus comparators. Risks were greatest in the first year after discharge and gradually decreased over time. CONCLUSIONS: Survivors of pediatric dialysis-treated AKI are at higher long-term risks of kidney failure, death, CKD, and hypertension, compared with a matched hospitalized cohort.

Health care utilization and costs following Kawasaki disease.

Objectives: Kawasaki disease (KD) is a common childhood vasculitis with increasing incidence in Canada. Acute KD hospitalizations are associated with high health care costs. However, there is minimal health care utilization data following initial hospitalization. Our objective was to determine rates of health care utilization and costs following KD diagnosis. Methods: We used population-based health administrative databases to identify all children (0 to 18 years) hospitalized for KD in Ontario between 1995 and 2018. Each case was matched to 100 nonexposed comparators by age, sex, and index year. Follow-up continued until death or March 2019. Our primary outcomes were rates of hospitalization, emergency department (ED), and outpatient physician visits. Our secondary outcomes were sector-specific and total health care costs. Results: We compared 4,597 KD cases to 459,700 matched comparators. KD cases had higher rates of hospitalization (adjusted rate ratio 2.07, 95%CI 2.00 to 2.15), outpatient visits (1.30, 95%CI 1.28 to 1.33), and ED visits (1.22, 95%CI 1.18 to 1.26) throughout follow-up. Within 1 year post-discharge, 717 (15.6%) KD cases were re-hospitalized, 4,587 (99.8%) had ≥1 outpatient physician visit and 1,695 (45.5%) had ≥1 ED visit. KD cases had higher composite health care costs post-discharge (e.g., median cost within 1 year: $2466 CAD [KD cases] versus $234 [comparators]). Total health care costs for KD cases, respectively, were $13.9 million within 1 year post-discharge and $54.8 million throughout follow-up (versus $2.2 million and $23.9 million for an equivalent number of comparators). Conclusions: Following diagnosis, KD cases had higher rates of health care utilization and costs versus nonexposed children. The rising incidence and costs associated with KD could place a significant burden on health care systems.

Incidence and short-term outcomes of Kawasaki disease.

OBJECTIVE: Kawasaki disease (KD) is a childhood vasculitis with conflicting reported North American trends in incidence and patient characteristics. OBJECTIVES: (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. METHODS: 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. RESULTS: 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. CONCLUSIONS: KD incidence is increasing in Ontario, with greater healthcare utilization from hospitalizations and subsequent follow-up. IMPACT: 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.

Post-transplant malignancies in pediatric organ transplant recipients.

The majority of cancer diagnoses in pediatric solid organ transplant recipients (SOTRs) are post-transplantation lymphoproliferative disorders (PTLD) or skin cancers. However, pediatric SOTRs are also at significantly elevated risk for multiple other solid and hematological cancers. The risks of specific cancers vary by transplanted organ, underlying disease, and immunosuppression factors. More than one-quarter of pediatric SOTRs develop cancer within 30 years of transplantation and their risk of solid cancer is 14 times greater than the general population. Pediatric SOTRs are at significantly higher risk of cancer-associated death. Improving patient survival among pediatric SOTRs puts them at risk of adult epithelial cancers associated with environmental carcinogenic exposures. Vaccination against oncogenic viruses and avoidance of excessive immunosuppression may reduce the risk of solid cancers following transplantation. Patient and family education regarding photoprotection is an essential component of skin cancer prevention. There is significant variability in cancer screening recommendations for SOTRs and general population approaches are typically not validated for transplant populations. An individualized approach to cancer screening should be developed based on estimated cancer risk, patient life expectancy, and screening test performance.

Malignancies after pediatric solid organ transplantation.

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.

Serum Creatinine Monitoring After Acute Kidney Injury in the PICU.

OBJECTIVES: It is unknown whether children with acute kidney injury during PICU admission have kidney function monitored after discharge. Objectives: 1) describe postdischarge serum creatinine monitoring after PICU acute kidney injury and 2) determine factors associated with postdischarge serum creatinine monitoring. DESIGN: Secondary analysis of longitudinal cohort study data. SETTING: Two PICUs in Montreal and Edmonton, Canada. PATIENTS: Children (0-18 yr old) surviving PICU admission greater than or equal to 2 days from 2005 to 2011. Exclusions: postcardiac surgery and prior kidney disease. Exposure: acute kidney injury by Kidney Disease: Improving Global Outcomes serum creatinine definition. INTERVENTIONS: None. MEASUREMENTS: Primary outcome: postdischarge serum creatinine measured by 90 days, 1 year, and 5-7 years. SECONDARY OUTCOMES: Healthcare events and nephrology follow-up. ANALYSIS: Proportions with outcomes; logistic regression to evaluate factors associated with the primary outcome. Kaplan-Meier analysis of time to serum creatinine measurement and healthcare events. MAIN RESULTS: Of n = 277, 69 (25%) had acute kidney injury; 29/69 (42%), 34/69 (49%), and 51/69 (74%) had serum creatinine measured by 90 days, 1 year, and 5-7 year postdischarge, respectively. Acute kidney injury survivors were more likely to have serum creatinine measured versus nonacute kidney injury survivors at all time points (p ≤ 0.01). Factors associated with 90-day serum creatinine measurement were inpatient nephrology consultation (unadjusted odds ratio [95% CI], 14.9 [1.7-127.0]), stage 2-3 acute kidney injury (adjusted odds ratio, 3.4 [1.1-10.2]), and oncologic admission diagnosis (adjusted odds ratio, 10.0 [1.1-93.5]). A higher proportion of acute kidney injury versus nonacute kidney injury survivors were readmitted by 90 days (25 [36%] vs 44 [21%]; p = 0.01) and 1 year (33 [38%] vs 70 [34%]; p = 0.04). Of 24 acute kidney injury survivors diagnosed with chronic kidney disease or hypertension at 5-7 year follow-up, 16 (67%) had serum creatinine measurement and three (13%) had nephrology follow-up postdischarge. CONCLUSIONS: Half of PICU acute kidney injury survivors have serum creatinine measured within 1-year postdischarge and follow-up is suboptimal for children developing long-term kidney sequelae. Knowledge translation strategies should emphasize the importance of serum creatinine monitoring after childhood acute kidney injury.

Long-term outcomes and disease course of children with juvenile idiopathic arthritis in the ReACCh-Out cohort: a two-centre experience.

OBJECTIVE: To assess long-term outcomes of children with JIA diagnosed in the biologic era. METHODS: Chart review of patients prospectively enrolled in the Research in Arthritis in Canadian Children Emphasizing Outcomes inception cohort at two Canadian centres. Inactive disease and remission were defined according to Wallace criteria. RESULTS: We included 247 of 254 (97%) eligible patients diagnosed 2005-10. At the last follow-up visit at a median age of 16.9 years, 47% were in remission off medications, 25% in remission on medications and 27% had active disease; 51% were on at least one anti-rheumatic medication (22% on biologics). Patients with systemic JIA had the highest frequency of remission off medications (70%) and patients with RF-positive polyarthritis had the lowest (18%) (P <0.05 by Fisher's exact test). Among 99 patients with oligoarthritis at enrolment, 14 (14%) had an oligoarthritis extended course. Forty-five patients (18%) had at least one erosion or joint space narrowing in X-rays or MRI, and two (0.8%) required joint replacement. CONCLUSION: Relative to historical cohorts, this study suggests a reduction in JIA permanent damage, a more favourable prognosis for systemic JIA and a lower progression to oligoarthritis extended category. However, in an era of biologic therapy, one in four patients with JIA still enter adulthood with active disease and one in two still on treatment.

Changing trends in total knee replacement.

INTRODUCTION: This study evaluates a possible change in the demographics and surgical practice observed in a large cohort of patients undergoing total knee replacement (TKR). PATIENTS AND METHODS: We performed a retrospective analysis of a prospectively collected data on two groups of consecutive patients undergoing primary TKR. Group one consisted of patients who underwent surgery between 1994 and 1998. Group two consisted of patients who had surgery between 2009 and 2012. RESULTS: The mean age of group two was significantly greater than that of group one: 68.9 years (68.1-69.7 years) for group one versus 70.1 years (69.6-70.6 years) for group two (p = 0.009). The mean BMI of group two was significantly greater than that of group one: 29.5 kg/m2 (29.0-29.9 kg/m2) for group one versus 32.0 kg/m2 (31.7-32.3 kg/m2) for group two (p < 0.001). The mean pain component of the AKSS was significantly worse in group one than in group two: 28.6 (27.2-30.0) for group one versus 35.5 (34.6-36.4) for group two (p < 0.001). The mean function component of the AKSS was significantly worse in group one than in group two: 48.6 (47.3-49.9) for group one versus 51.5 (50.7-52.3) for group two (p < 0.001). CONCLUSION: This study describes the change in demographics of patients undergoing TKR in our institution over the last two decades.

Renal Implications of Long-Term Systemic Bevacizumab for Recurrent Respiratory Papillomatosis.

BACKGROUND: Bevacizumab is a vascular endothelial growth factor (VEGF) inhibitor that is used off-label for select cases of recurrent respiratory papillomatosis (RRP) that are severe, involve the distal airway or lung parenchyma, and refractory to other forms of adjuvant therapy. However, there is limited safety data for the use of bevacizumab in children and VEGF inhibitors are reported to have a range of adverse renal effects, including hypertension, proteinuria, and thrombotic microangiopathy (TMA). CASE-DIAGNOSIS/TREATMENT: This report describes a case of severe juvenile-onset RRP that had an exceptionally high operative burden that was refractory to several adjuvant treatment strategies (including intralesional cidofovir and subcutaneous pegylated interferon). Bevacizumab treatment resulted in a dramatic and sustained improvement in disease control over a 5-year period. However, after 3 years of treatment, the patient developed hypertension and proteinuria and was found to have evidence of a glomerular TMA on kidney biopsy. These complications were successfully managed with a reduction in bevacizumab frequency and angiotensin-converting enzyme inhibitor initiation. CONCLUSIONS: Clinicians caring for children treated with VEGF inhibitors should be aware of the potential renal complications and their management.

Long-Term Cardiovascular Outcomes in Children and Adolescents With Hypertension.

Importance: Hypertension affects 6% of all children, and its prevalence is increasing. Childhood hypertension tracks into adulthood and is associated with subclinical cardiovascular disease; however, there is a lack of evidence linking childhood hypertension to cardiovascular outcomes, which may contribute to underdiagnosis and undertreatment. Objective: To determine the long-term associated risk of major adverse cardiac events (MACE) among children diagnosed with hypertension. Design, Setting, and Participants: This was a population-based, retrospective, matched cohort study conducted from 1996 to 2022. The study included all children (aged 3-18 years) alive in Ontario, Canada, from 1996 to 2021, who were identified using provincial administrative health databases. Children with prior kidney replacement therapy were excluded. Exposure: Incident hypertension diagnosis, identified by validated case definitions using diagnostic and physician billing claims. Each case was matched with 5 controls without hypertension by age, sex, birth weight, maternal gestational hypertension, prior comorbidities (chronic kidney disease, diabetes, cardiovascular surgery), and a propensity score for hypertension. Main Outcomes and Measures: The primary outcome was MACE (a composite of cardiovascular death, stroke, hospitalization for myocardial infarction or unstable angina, or coronary intervention). Time to MACE was evaluated using the Kaplan-Meier method and Cox proportional hazards regression. Results: A total of 25 605 children (median [IQR] age, 15 [11-17] years; 14 743 male [57.6%]) with hypertension were matched to 128 025 controls without hypertension. Baseline covariates were balanced after propensity score matching, and prior comorbidities were uncommon (hypertension vs control cohort: malignancy, 1451 [5.7%] vs 7908 [6.2%]; congenital heart disease, 1089 [4.3%] vs 5408 [4.2%]; diabetes, 482 [1.9%] vs 2410 [1.9%]). During a median (IQR) of 13.6 (7.8-19.5) years of follow-up, incidence of MACE was 4.6 per 1000 person-years in children with hypertension vs 2.2 per 1000 person-years in controls (hazard ratio, 2.1; 95% CI, 1.9-2.2). Children with hypertension were at higher associated risk of stroke, hospitalization for myocardial infarction or unstable angina, coronary intervention, and congestive heart failure, but not cardiovascular death, compared with nonhypertensive controls. Conclusions and Relevance: Children diagnosed with hypertension had a higher associated long-term risk of MACE compared with controls without hypertension. Improved detection, follow-up, and control of pediatric hypertension may reduce the risk of adult cardiovascular disease.