Reducing Unnecessary Imaging in Children With Multicystic Dysplastic Kidney or Solitary Kidney.

BACKGROUND AND OBJECTIVES: Children with isolated unilateral multicystic dysplastic kidney (MCDK) or congenital solitary kidney (CSK) undergo serial renal ultrasonography with variable frequency until they are transitioned to adult care. A growing body of literature suggests the value of frequent ultrasonography in this population is limited, providing no benefit to overall outcomes. Despite emerging evidence, ultrasound remains overused, resulting in avoidable health care expenditures and unnecessary use of resources. With our initiative, we aimed to improve quality of care by reducing avoidable ultrasounds in these children. METHODS: This was a single-center, prospective, interrupted time series of children <18 years with ultrasound-confirmed isolated unilateral MCDK or CSK in the outpatient nephrology clinic to evaluate the effect of a decision-making algorithm on the proportion of children receiving an avoidable ultrasound. An algorithm depicting a consensus, evidence-based protocol for managing pediatric MCDK or CSK was refined through content expert feedback and usability testing to standardize frequency of ultrasonography. Ultrasounds were deemed necessary after birth, at 6 months, and at 2, 5, 10, and 15 years. Differences pre- and postintervention were determined by using a U chart and t and F tests for significance. RESULTS: The algorithm resulted in a 47% reduction (P < .001) in the proportion of avoidable ultrasounds ordered in children with MCDK and CSK. This reduction was sustainable over a 6-month period and would result in at least $46 000 annual savings. CONCLUSIONS: Introduction of a clinical decision-making algorithm was associated with a reduction in avoidable ultrasound testing. Improving adherence across providers may allow for an even more pronounced reduction.

Impact of steroids and steroid-sparing agents on quality of life in children with nephrotic syndrome.

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.

Prediction of Short- and Long-Term Outcomes in Childhood Nephrotic Syndrome.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Association of low birth weight and prematurity with clinical outcomes of childhood nephrotic syndrome: a prospective cohort study.

BACKGROUND: Low birth weight (LBW)/prematurity have been proposed as risk factors for the development of kidney disease in adulthood. Whether there is an association between LBW/prematurity and poor renal outcomes in childhood onset nephrotic syndrome remains unknown. METHODS: Children with nephrotic syndrome diagnosed between 1 and 18 years of age were followed prospectively from 1996 to 2016 at The Hospital for Sick Children (N = 377). LBW/prematurity was defined as birth weight < 2500 g or gestational age < 36 weeks. Normal birth weight (NBW) was defined as birth weight ≥ 2500 g. Measures evaluating clinical course of nephrotic syndrome include initial steroid-resistant nephrotic syndrome (SRNS), time to first relapse, and frequently relapsing nephrotic syndrome. Kaplan-Meier survival analysis, logistic regression, and Cox proportional hazards regression were used to determine the association of LBW/prematurity with clinical outcomes. RESULTS: Median birth weights in LBW/premature (n = 46) and NBW (n = 331) children were 2098 g (interquartile range [IQR] 1700-2325 g) and 3317 g (IQR 2977-3685 g), respectively. Odds of having SRNS were 3.78 (95% confidence interval [CI] 1.28-11.21) times higher among LBW/premature children than NBW children. An 8% decrease in odds of developing SRNS was observed for every 100 g increase in birth weight (adjusted odds ratio [OR] 0.92; 95% CI 0.86-0.98). Median time to first relapse did not differ (hazard ratio [HR] 0.89; 95% CI 0.53-1.16). CONCLUSIONS: LBW/premature children were more likely to develop SRNS but did not have a difference in time to first relapse with NBW children. Understanding the impact and mechanism of birth weight and steroid-resistant disease needs further study.

Prevalence of Asthma and Allergies and Risk of Relapse in Childhood Nephrotic Syndrome: Insight into Nephrotic Syndrome Cohort.

OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSIONS: Two-thirds of children with nephrotic syndrome at presentation have allergic symptoms and asthma; however, neither are associated with an increased frequency of relapses.

Parental Health Literacy and Outcomes of Childhood Nephrotic Syndrome.

OBJECTIVE: Determine the association of parental health literacy with treatment response among children with nephrotic syndrome. METHODS: This was a cohort study of children aged 1-18 with nephrotic syndrome and their parent. Health literacy was measured using the validated Short Test of Functional Health Literacy in Adults assessing reading comprehension and numeracy. Outcomes included initial relapse-free period, frequently relapsing disease, relapse rate, second-line medication use, and complete remission after therapy. RESULTS: Of 190 parents, 80% had adequate health literacy (score >67 of 100), and higher scores were not correlated with higher education. Almost all achieved perfect numeracy scores (>86%); numeracy was not associated with outcomes. After adjusting for immigration, education, and income, higher reading comprehension scores (tertile 3) compared with lower scores (tertile 1) were significantly associated with lower risk of first relapse (hazard ratio 0.67, 95% confidence interval [CI] 0.48-0.94, P trend = .02), lower odds of frequently relapsing disease (odds ratio [OR] 0.38, 95% CI 0.21-0.70, P trend = .002), lower relapse rate (rate ratio 0.77, 95% CI 0.73-0.80, P trend < .001), and higher odds of complete remission after both initial steroids and cyclophosphamide (OR 2.07, 95% CI 1.36-3.16, P trend = .003; OR 5.97, 95% CI 2.42-14.7, P trend < .001). CONCLUSIONS: Lower parental health literacy, specifically reading comprehension, is associated with higher relapse rates among children with nephrotic syndrome and fewer achieving complete remission. This underscores the importance of assessing and targeting health literacy for chronic management of childhood-onset diseases.

Parental attitudes to genetic testing differ by ethnicity and immigration in childhood nephrotic syndrome: a cross-sectional study.

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.

MISE EN CONTEXTE: Des études aux États-Unis font état de différences d'opinions parmi les parents provenant de différentes origines ethniques quant à la possibilité de procéder à des tests de dépistage génétique sur leurs enfants. Toutefois il n'existe aucune étude qui traite de cette question au sein des différents groupes ethniques au Canada. OBJECTIFS DE L'ÉTUDE: L'étude avait pour but de vérifier si l'origine ethnique ou le statut d'immigrant des parents influençait leur façon d'aborder la question du dépistage génétique pour la détection d'une néphropathie potentiellement évolutive chez leur enfant. CADRE ET TYPE D'ÉTUDE: Cette étude transversale s'est tenue dans la grande région de Toronto au Canada. PARTICIPANTS: Il s'agit de 320 parents d'enfants âgés de 1 à 18 ans atteints d'un syndrome néphrotique qui participaient à l'étude de cohorte observationnelle INSIGHT (Insight into Nephrotic Syndrome: Investigating Genes Health and Therapeutics). MESURES: Les données soit la répartition démographique l'origine ethnique ou le statut d'immigrant des parents, les éléments propres à l'enfant ainsi que le niveau d'intérêt des parents à l'égard des tests de dépistage génétique, ont été colligées à partir d'un questionnaire remis aux parents lors de la première visite. MÉTHODOLOGIE: Des modèles de régression logistique ont été utilisés pour établir un parallèle entre l'origine ethnique ou le statut d'immigrant d'un parent et son intérêt à soumettre son enfant à un dépistage génétique. RÉSULTATS: La majorité des participants à l'étude (85 %) démontrait un intérêt envers la possibilité de soumettre leur enfant à un test de dépistage génétique. Toutefois dans le cas précis des gens originaires de l'Asie du Sud et de ceux provenant de l'Extrême-Orient ou de l'Asie du Sud-Est, les probabilités de consentir à un tel test étaient respectivement de 74 % et de 76 % plus faibles que pour les gens d'origine européenne. (Risque relatif [RR] : 0,26 à 95 % d'intervalle de confiance [IC] : 0.10-0.68; RR : 0,24 à 95 % IC : 0.07-0.79 respectivement). Ces résultats ont été obtenus après l'exclusion d'indicateurs relatifs à l'âge et au sexe de l'enfant, au sexe et au niveau d'éducation des parents, à la résistance de l'enfant au traitement initial par les stéroïdes et à la durée du séjour au Canada. Cette observation s'est également confirmée chez les immigrants reçus, pour qui la probabilité de consentir à un tel test pour leur enfant s'est aussi avérée significativement moins élevée après l'application des mêmes correctifs (RR : 0,29, à 95 % IC : 0.12-0.72). Aucune corrélation n'a pu être établie entre le niveau d'éducation élevé des parents et un intérêt accru à soumettre leur enfant à un test de dépistage génétique (RR : 1,24 à 95 % IC : 0.64-2.42). LIMITES DE L'ÉTUDE: Les résultats sont limités du fait que les participants avaient consenti à soumettre leur enfant à un test de dépistage génétique fà des fins de recherche dans le cadre de leur inclusion à l'étude INSIGHT. CONCLUSIONS: Alors que la majorité des parents ayant participé à l'étude voyait d'un bon œil la possibilité de soumettre leur enfant à un test de dépistage génétique les immigrants reçus ainsi que les participants originaires de l'Asie du Sud, de l'Extrême-Orient et de l'Asie du Sud-Est se sont avérés plus susceptibles de décliner l'offre. Par conséquent, le processus de consultation en génétique doit être adapté pour mieux répondre aux inquiétudes et aux préoccupations de ces groupes de parents; ceci afin de tirer le meilleur parti d'une prise de décision éclairée dans un contexte clinique.

Pleuropulmonary blastoma in a child with autosomal-recessive polycystic kidney disease.

Autosomal-recessive polycystic kidney disease (ARPKD) is a developmental disorder known to affect both the kidneys and the liver. Renal involvement results in progressive renal insufficiency and hypertension, while hepatic involvement can result in portal hypertension and cholangitis. Pulmonary abnormalities relate mainly to pulmonary insufficiency in those patients who present as neonates. We present a unique case of a child with ARPKD found to have a cystic lesion of the lung. Upon surgical resection, a pathological diagnosis of pleuropulmonary blastoma (PPB) was made. There are no previous reports in the literature describing the association of these two entities. Knowledge of this potential association is important in the clinical management of these children and may open new avenues of genetic research.

Possible role of new pressor protein in hypertensive anephric hemodialysis patients.

Unexplained hypertension was observed in three anephric children on hemodialysis. We investigated the possible involvement of a novel hypertensive extra-renal enzyme new pressor protein (NPP), related to coagulation beta-FXIIa. Currently, NPP activity can only be determined by a rat bioassay model. On study day 1, pre dialysis, patients 1, 2, and 3 were hypertensive and their plasmas raised rat systolic blood pressure (SBP) by 45, 34, and 9 mmHg, respectively. Post dialysis, patients 1 and 2 reached their estimated dry body weight and their systemic pressures dropped, while patient 3 remained hypertensive and hypervolemic. Their post-dialysis plasmas raised rat SBP by 22, 14, and 9 mmHg, respectively. On day 2, similar relationships between patient SBP, volume status, and plasma NPP-like activity in rats were observed. The characteristic rat BP responses, lack of inhibition by captopril (ruling out a renin-mediated effect), and inhibition by soybean trypsin inhibitor support co-identity with NPP. Plasma FXIIa (combined alpha-FXIIa and beta-FXIIa) was measured by immunoassay and found to be elevated in all patients. This investigation suggests that there is high endogenous NPP activity in the plasmas of these hypertensive hemodialysis patients, it changes with SBP and fluid volume, and is a possible contributor to their hypertension. Further studies are required to examine the wider applicability of these novel findings.