Immunosuppressive Therapy of Antibody-Mediated aHUS and TTP.

The recent classification of pediatric thrombotic microangiopathies (TMA) takes into consideration mechanisms of disease for guidance to targeted therapies. We present our experience with seven patients with antibody mediated atypical hemolytic uremic syndrome (aHUS) and thrombotic thrombocytopenic purpura (TTP). Five children had aHUS with antibodies against complement factor H (CFH-ab) and two with TTP with antibodies against metalloproteinase ADAMTS13. In the aHUS cases diagnosed and treated before the eculizumab era, CFH-ab was detected using the ELISA assay. Mutational analysis of selected complement genes was performed. TTP was diagnosed if, in addition to microangiopathic hemolytic anemia and thrombocytopenia, ischemic organ involvement and severe deficiency in ADAMTS13 activity were present. Treatment protocol consisted of plasma exchanges (PE) and steroid pulses, followed by the combination of cyclophosphamide and rituximab to achieve long-term immunosuppression. Four patients with CFH-ab and the TTP patients with ADAMTS13 antibodies came into sustained remission. After a median follow-up of 11.7 (range 7.7-12.9) years without maintenance therapy, no disease recurrence was observed; nevertheless, six patients, two had hypertension and two had proteinuria as a late consequence. One patient, with late diagnosis of CFH-ab and additional genetic risk factors who was treated only with PE and plasma substitution, reached end-stage renal disease and was later successfully transplanted using eculizumab prophylaxis. In the cases of antibody-mediated TMAs, PE and early immunosuppressive treatment may result in sustained remission with preserved kidney function. Further data are needed to establish optimal treatment of anti-FH antibody-associated HUS.

Subclinical cardiac dysfunction in pediatric kidney transplant recipients identified by speckle-tracking echocardiography.

BACKGROUND: Kidney transplantation (KTx) improves prognosis in children with kidney failure; still, these patients are prone to cardiovascular damage due to multiple risk factors. Our aim was to assess myocardial structure and function in pediatric KTx by conventional and speckle-tracking echocardiography (STE) in association with established cardiovascular risk factors. METHODS: Forty-two KTx and 39 healthy age- and gender-matched children were evaluated. KTx recipients were further categorized according to the control of hypertension assessed by 24-h ambulatory blood pressure monitoring (ABPM). Subjects underwent pulse wave velocity (PWV) measurement, conventional echocardiography, and 2-dimensional STE. Left and right ventricular (LV, RV) global longitudinal strain (GLS), and LV circumferential strain (GCS) were measured. Glomerular filtration rate (eGFR) was calculated according to the Schwartz formula. RESULTS: KTx patients had increased blood pressure and arterial stiffness. LV ejection fraction (EF) was preserved along with elevated LV mass index (LVMi) while LVGLS was significantly lower, whereas LVGCS and RVGLS were increased in KTx. Uncontrolled hypertensives had lower LVGLS compared to those with controlled hypertension. Using multiple forward stepwise regression analysis, 24-h SBP and relative wall thickness (RWT) were independent determinants of LVMi, whereas antihypertensive therapy, eGFR, and HOMA-IR were independent determinants of LVGLS. CONCLUSIONS: Cardiac morphology and function show distinct changes after KTx. Along with comparable ventricular volumes, LV hypertrophy and subclinical myocardial dysfunction are present. Control of hypertension and kidney graft function are major factors of LV performance. STE may be useful to reveal early myocardial dysfunction in pediatric KTx. A higher resolution version of the Graphical abstract is available as Supplementary information.

Pediatric radiology crossing continents.

This paper will discuss, from a subjective perspective, aspects of paediatric radiology in different parts of the world. A small survey was conducted to improve our understanding of radiologic care and to explore the current status of paediatric radiology worldwide. As part of this survey, the number of paediatric radiologists and radiologists was compared to the population and to the number of children in 34 countries. The number of paediatric radiologists varied between 0 and 50 per million children. In general, the proportion of paediatric radiologists compared to radiologists is poor, even in countries with an aging population. Unfortunately, developing countries are severely underserved in terms of radiology, while paediatric radiology is almost nonexistent. The author, based on her experiences as a volunteer paediatric radiologist in Malawi, India, Cambodia and Tanzania, highlights some of the difficulties in radiologic care in developing countries. The author's personal experiences and the survey both suggest that the need for paediatric radiology is high across the world, but the supply is not sufficient, especially in developing countries, when compared to developed countries.

Evaluation of a child with suspected nephrolithiasis.

PURPOSE OF REVIEW: As the incidence of nephrolithiasis in children doubles every 10 years it is becoming a common disease associated with significant morbidity along with considerable economic burden worldwide. The aim of this review is to summarize current data on the epidemiology and causes of renal stones in children and to provide a frame for the first clinical evaluation of a child with suspected nephrolithiasis. RECENT FINDINGS: Dietary and environmental factors are the driving force of changing epidemiology. Diagnosis should be based on medical history, presenting signs, examination, first laboratory and radiological workup. Ultrasound should be the initial diagnostic imaging performed in pediatric patients while low-dose computed tomography is rarely necessary for management. Metabolic factors including hypercalciuria, hypocitraturia, low fluid intake as well as specific genetic diseases should be explored after the resolution of initial signs and symptoms. SUMMARY: Appropriate initial evaluation, imaging technique, identification of risk factors and other abnormalities are essential for early diagnosis and prevention of stone-related morbidity in children with suspected nephrolithiasis.

Association between timing of dialysis initiation and clinical outcomes in the paediatric population: an ESPN/ERA-EDTA registry study.

BACKGROUND: There is no consensus regarding the timing of dialysis therapy initiation for end-stage kidney disease (ESKD) in children. As studies investigating the association between timing of dialysis initiation and clinical outcomes are lacking, we aimed to study this relationship in a cohort of European children who started maintenance dialysis treatment. METHODS: We used data on 2963 children from 21 different countries included in the European Society of Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry who started renal replacement therapy before 18 years of age between 2000 and 2014. We compared two groups according to the estimated glomerular filtration rate (eGFR) at start: eGFR ≥8 mL/min/1.73 m2 (early starters) and eGFR <8 mL/min/1.73 m2 (late starters). The primary outcomes were patient survival and access to transplantation. Secondary outcomes were growth and cardiovascular risk factors. Sensitivity analyses were performed to account for selection- and lead time-bias. RESULTS: The median eGFR at the start of dialysis was 6.1 for late versus 10.5 mL/min/1.73 m2 for early starters. Early starters were older [median: 11.0, interquartile range (IQR): 5.7-14.5 versus 9.4, IQR: 2.6-14.1 years]. There were no differences observed between the two groups in mortality and access to transplantation at 1, 2 and 5 years of follow-up. One-year evolution of height standard deviation scores was similar among the groups, whereas hypertension was more prevalent among late initiators. Sensitivity analyses resulted in similar findings. CONCLUSIONS: We found no evidence for a clinically relevant benefit of early start of dialysis in children with ESKD. Presence of cardiovascular risk factors, such as high blood pressure, should be taken into account when deciding to initiate or postpone dialysis in children with ESKD, as this affects the survival.

Cardiovascular Risk Assessment in Pediatric Liver Transplant Patients.

OBJECTIVES: Cardiovascular (CV) diseases play a leading role in the mortality of adult liver transplant (LT) recipients. However, data regarding CV risk factors in children after LT remain sparse. The present study assessed the presence of CV risk factors and signs of CV impairment in LT children. METHODS: A total of 42 LT recipients (21 men, age 9.93 ±â€Š3.57 years) were studied. Body composition [body mass index standard deviation score, percentage of body fat (by bioimpedance analysis)], lipid profiles, glycemic control, blood pressure, and arterial stiffness [assessed by aortic pulse wave velocity (PWV)] were evaluated. The effect of different treatment modalities [tacrolimus (TAC) (n = 30) or cyclosporine (CyA) (n = 11)] was also analyzed. RESULTS: Almost 18% of children were overweight or obese. Patients on TAC had a significantly higher body fat mass and percentage of body fat compared with the CyA group (P < 0.02). Borderline to high lipid values were present in 40% of patients. Children on CyA had higher serum cholesterol levels compared to TAC (P < 0.004). Nineteen percent of patients had hypertension. Half of the patients had glomerular filtration rate values <90 mL/min/1.73 m, whereas PWV values were above the 95th percentile in 12%. CONCLUSIONS: Increased body fat, chronic kidney disease, high lipid content, hypertension, and increased arterial stiffness are already present and are in part related to the type of immunosuppression regimen in LT children >5 years following transplantation. Long-term follow-up is needed to evaluate their impact on CV health and survival.

Use of subcutaneous treprostinil in pediatric pulmonary arterial hypertension-Bridge-to-transplant or long-term treatment?

PAH is a progressive life-threatening disease in children. While parenteral prostacyclin therapy improves survival in patients with severe PAH, central line-related complications are common. Our aim was to assess the efficacy, safety, and tolerability of subcutaneous treprostinil treatment in pediatric PAH patients. Eight patients were treated with subcutaneous treprostinil at the Pediatric Heart Center Budapest. Indications for subcutaneous treprostinil therapy were clinical worsening and/or echocardiographic progression or switch from intravenous to subcutaneous therapy. Following treprostinil initiation, clinical status improved or did not change in four of eight patients. Two patients were lost early during treprostinil therapy, parenteral treprostinil as a rescue therapy being insufficient in these cases. The final dose in long-term treated patients was between 60 and 100 ng/kg/min. Aside from thrombocytopenia, other severe side effects were not observed. Potts shunt was performed as palliative treatment in two cases. Three patients had successful lung transplantation, and one died while on the waiting list. Long-term subcutaneous treprostinil could be a safe and well-tolerated therapy in children with severe PAH even at higher doses. It may serve as an alternative to intravenous prostacyclin treatment allowing to avoid the potential complications of permanent central line placement.

Cardiac Magnetic Resonance Imaging of the Myocardium in Chronic Kidney Disease.

Early stages of chronic kidney disease (CKD) are often underdiagnosed, while their deleterious effects on the cardiovascular (CV) system are already at work. Thus, the assessment of early CV damage is of crucial importance in preventing major CV events. Myocardial fibrosis is one of the major consequences of progressive CKD, as it may lead to reentry arrhythmias and long-term myocardial dysfunction predisposing to sudden death and/or congestive heart failure. Subclinical myocardial fibrosis, with a potential key role in the development of uraemic cardiac disease, can be measured and characterised by appropriate cardiac magnetic resonance (CMR) techniques. Fibrosis detection was initially based on the contrast agent gadolinium, due to the superiority in sensitivity and accuracy of contrast-based methods in fibrosis assessment relative to native techniques. However, the severe consequences of gadolinium administration in uraemia (nephrogenic systemic fibrosis) have forced practitioners to re-evaluate the methodology. In the present overview, we review the possible contrast-based and contrast agent-free CMR techniques, including native T1 relaxation time, extracellular volume and global longitudinal strain measurement. The review also summarises their potential clinical relevance in CKD patients based on recently published studies.

Longitudinal Deformation of the Right Ventricle in Hypoplastic Left Heart Syndrome: A Comparative Study of 2D-Feature Tracking Magnetic Resonance Imaging and 2D-Speckle Tracking Echocardiography.

In hypoplastic left heart syndrome (HLHS), long-term outcome is closely related to right ventricular function. Echocardiography and magnetic resonance imaging (MRI) are routinely used for functional assessment. MRI 2D-tissue feature tracking (2D-FT) allows quantification of myocardial deformation but has not yet been applied to HLHS patients. We sought to investigate the feasibility of this technique and to compare the results to 2D-speckle tracking echocardiography (2D-STE). In routine MRI 2D anatomical four chamber view, cine images were recorded in 55 HLHS patients (median age 4.9 years [1.6, 17.0]). Regional and global peak systolic longitudinal strain (LS) and strain rate (LSR) were determined using 2D-FT software. Echocardiographic four chamber view was analyzed with 2D-STE. Visualization of all myocardial segments with MRI was excellent, regional, and global LS and LSR could be assessed in all data sets. In 2D-STE, 28% of apical segments could not be analyzed due to poor image quality. Agreement of 2D-FT MRI and 2D-STE was acceptable for global LS, but poor for global LSR. In MRI, regional LS was lower in the septal segments, while LSR was not different between the segments. GLS and GLSR correlated with ejection fraction (GLS: r = - 0.45 and r < 0.001, GLSR: r = - 0.34 and p = 0.01). With new post-processing options, the assessment of regional and global LS and LSR is feasible in routine MRI of HLHS patients. For LS, results were comparable with 2D-STE. The agreement was poor for LSR, which might relate to differences in temporal resolution between the two imaging modalities.

Microarray Analysis Reveals Increased Expression of Matrix Metalloproteases and Cytokines of Interleukin-20 Subfamily in the Kidneys of Neonate Rats Underwent Unilateral Ureteral Obstruction: A Potential Role of IL-24 in the Regulation of Inflammation and Tissue Remodeling.

BACKGROUND/AIMS: Congenital obstructive nephropathy (CON) is the main cause of pediatric chronic kidney diseases leading to renal fibrosis. High morbidity and limited treatment opportunities of CON urge the better understanding of the underlying molecular mechanisms. METHODS: To identify the differentially expressed genes, microarray analysis was performed on the kidney samples of neonatal rats underwent unilateral ureteral obstruction (UUO). Microarray results were then validated by real-time RT-PCR and bioinformatics analysis was carried out to identify the relevant genes, functional groups and pathways involved in the pathomechanism of CON. Renal expression of matrix metalloproteinase (MMP)-12 and interleukin (IL)-24 were evaluated by real-time RT-PCR, flow cytometry and immunohistochemical analysis. Effect of the main profibrotic factors on the expression of MMP-12 and IL-24 was investigated on HK-2 and HEK-293 cell lines. Finally, the effect of IL-24 treatment on the expression of pro-inflammatory cytokines and MMPs were tested in vitro. RESULTS: Microarray analysis revealed 880 transcripts showing >2.0-fold change following UUO, enriched mainly in immune response related processes. The most up-regulated genes were MMPs and members of IL-20 cytokine subfamily, including MMP-3, MMP-7, MMP-12, IL-19 and IL-24. We found that while TGF-ß treatment inhibits the expression of MMP-12 and IL-24, H2O2 or PDGF-B treatment induce the epithelial expression of MMP-12. We demonstrated that IL-24 treatment decreases the expression of IL-6 and MMP-3 in the renal epithelial cells. CONCLUSIONS: This study provides an extensive view of UUO induced changes in the gene expression profile of the developing kidney and describes novel molecules, which may play significant role in the pathomechanism of CON.

Bone metabolism and arterial stiffness after renal transplantation.

BACKGROUND/AIMS: To assess the relationship between bone and vascular disease and its changes over time after renal transplantation. Metabolic bone disease (MBD) is common in chronic kidney disease (CKD) and is associated with cardiovascular (CV) disease. Following transplantation (Tx), improvement in CV disease has been reported; however, data regarding changes in bone disease remain controversial. METHODS: Bone turnover and arterial stiffness (pulse wave velocity (PWV)) were assessed in 47 Tx patients (38 (3-191) months after Tx). RESULTS: Bone alkaline phosphatase (BALP), osteocalcin (OC) and beta-crosslaps were significantly higher in Tx patients, and decreased significantly after one year. There was a negative correlation between BALP, OC and steroid administered (r = -0.35; r = -0.36 respectively). PWV increased in the Tx group (1.15 SD). In patients with a follow up of <24 months, PWV was correlated with BALP and beta-crosslaps (r=0.53; r = 0.69 respectively) while in the ≥24 months group, PWV was correlated with cholesterol (r=0.38). CONCLUSIONS: Increased bone turnover and arterial stiffness are present following kidney transplantation. While bone turnover decreases with time, arterial stiffness correlates initially with bone turnover, after which the influence of cholesterol becomes significant. Non-invasive estimation of bone metabolism and arterial stiffness may help to assess CKD-MBD following renal transplantation.

[Ultrasound examination in childhood: new perspectives]. / Ultrahangvizsgálatok gyermekkorban: lehetoségek, új utak.

Everyday use of the modern imaging techniques such as CT, MRI, isotope, PET/CT decreased the reputation and importance of ultrasound. In some cases, ultrasound is only the first exploratory imaging method. Using the latest multi-slice CT, imaging can be performed in seconds, which led to a dramatic increase in the number of CT exams. However, this also means a significant radiation exposure to children, while US still harmless in this regard. In addition, significant progress has been made in ultrasound technology in recent years, which led an improvement in image quality. Children are ideal subjects for US examination as they usually have smaller weight with less body fat. Thus, ultrasound examination is easy to perform with a high frequency transducer resulting in much more detailed and higher resolution than in adults. With adequate equipment and experienced examiner in pediatric radiology, almost all parts of the body can be examined, making this technique as the first (sometimes together with X-ray) and, in most cases, the ultimate imaging exam for the diagnosis. This article will discuss the possibilities where ultrasound performed with a modern device is sufficient for an accurate diagnosis.

Ambulatory arterial stiffness index in children after kidney transplantation.

Given the increase in CV morbidity after RTx and the scarcity of CV events in pediatrics, surrogate markers should be assessed to characterize CV damage in this population. AASI is a marker of arterial stiffness in adults, predicting cardio- and cerebrovascular morbidity. Our aim was to assess the determinants of AASI in RTx children (n = 54, 15.5 ± 3.5 yr) and to examine its relationship to central PWV. AASI was calculated from 24 h ABPM. PWV was determined by applanation tonometry, body composition by multifrequency bioimpedance measurement. The dipping state, volume overload, and time on dialysis were the main predictors of AASI (p < 0.05). Children with established HT (n = 34) had increased AASI, extracellular body water, and BNP (p < 0.05). In contrast to AASI, PWV did not differ between HT and normotensive RTx patient groups. There was no correlation between AASI and PWV. PWV was increased in children who spent more than one yr on dialysis prior to RTx. In conclusion, increased AASI in HT RTx children better characterizes the actual volume- and pressure-dependent arterial rigidity rather than long-term morphological changes in large arteries as reflected by PWV.

Cardiovascular risk assessment in children with chronic kidney disease.

Chronic kidney disease (CKD) is a major factor contributing to cardiovascular (CV) morbidity and mortality with the highest risk in patients on dialysis. An estimation of CV risk is important not only to identify potential modifiable risk factors but also to evaluate the effect of treatments aimed to reduce the risk. Non-invasive methods of measuring vascular changes and circulating biomarkers are available to assess the presence and severity of cardiovascular damage. These include measures of structural (carotid intima-media thickness and coronary artery calcification score) and functional (aortic pulse wave velocity, 24-h ambulatory blood pressure monitoring, ambulatory arterial stiffness index, heart rate variability and flow-mediated dilatation) changes in the vessel wall. In addition, a number of circulating biomarkers of vascular damage and its progression have been studied. Many of these tests are well validated as surrogate markers of future cardiovascular events and death in adult CKD patients, but need technical adaptation, standardization and validation for use in children. With our current state of knowledge, these are best reserved for research studies and scarce clinical resources may be better utilized for preventative strategies to reduce the modifiable risk factors for calcification from early CKD stages.

Get to the heart of pediatric kidney transplant recipients: Evaluation of left- and right ventricular mechanics by three-dimensional echocardiography.

Background: Kidney transplantation (KTX) markedly improves prognosis in pediatric patients with end-stage kidney failure. Still, these patients have an increased risk of developing cardiovascular disease due to multiple risk factors. Three-dimensional (3D) echocardiography allows detailed assessment of the heart and may unveil distinct functional and morphological changes in this patient population that would be undetectable by conventional methods. Accordingly, our aim was to examine left- (LV) and right ventricular (RV) morphology and mechanics in pediatric KTX patients using 3D echocardiography. Materials and methods: Pediatric KTX recipients (n = 74) with median age 20 (14-26) years at study enrollment (43% female), were compared to 74 age and gender-matched controls. Detailed patient history was obtained. After conventional echocardiographic protocol, 3D loops were acquired and measured using commercially available software and the ReVISION Method. We measured LV and RV end-diastolic volumes indexed to body surface area (EDVi), ejection fraction (EF), and 3D LV and RV global longitudinal (GLS) and circumferential strains (GCS). Results: Both LVEDVi (67 ± 17 vs. 61 ± 9 ml/m2; p < 0.01) and RVEDVi (68 ± 18 vs. 61 ± 11 ml/m2; p < 0.01) were significantly higher in KTX patients. LVEF was comparable between the two groups (60 ± 6 vs. 61 ± 4%; p = NS), however, LVGLS was significantly lower (-20.5 ± 3.0 vs. -22.0 ± 1.7%; p < 0.001), while LVGCS did not differ (-29.7 ± 4.3 vs. -28.6 ± 10.0%; p = NS). RVEF (59 ± 6 vs. 61 ± 4%; p < 0.05) and RVGLS (-22.8 ± 3.7 vs. -24.1 ± 3.3%; p < 0.05) were significantly lower, however, RVGCS was comparable between the two groups (-23.7 ± 4.5 vs. -24.8 ± 4.4%; p = NS). In patients requiring dialysis prior to KTX (n = 64, 86%) RVGCS showed correlation with the length of dialysis (r = 0.32, p < 0.05). Conclusion: Pediatric KTX patients demonstrate changes in both LV and RV morphology and mechanics. Moreover, the length of dialysis correlated with the contraction pattern of the right ventricle.

Cardiovascular risk assessment in children following kidney transplantation.

CV diseases are the leading cause of death among patients with ESRD. RTX decreases the CV risk; however, it still remains definitely higher than that of the general population. Large multicenter and longitudinal studies are difficult to perform and hard end-points of CV events are usually missing among pediatric population. Thus, appropriate estimation of CV risk is of crucial importance to define the potential hazards and to evaluate the effect of treatments aimed to reduce the risk. A number of validated non-invasive methods are available to assess the extent of CV damage in adults, such as calcification scores, cIMT, aPWV, 24-h ABPM, AASI, and HRV; however, they need adaptation, standardization, and validation in pediatric studies. cIMT and PWV are the most promising methods, as pediatric normative values are already present. The up-to-date treatment of ESRD aims not only to save life, but to offer the patient a life expectancy approaching that of the healthy population and to ensure a reasonable quality of life.

Assessment of Quality of Life in Children With Pulmonary Hypertension Using Parent and Self-report Questionnaires.

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by elevation of pulmonary vascular resistance and right ventricular failure. By using advanced therapies to reduce mortality, clinicians focus on improving functional status and quality of life (QOL). The aim of our study was to assess health-related QOL of pediatric patients with PAH. Parents of all children (aged 2-18 years) and patients aged 5-18 years with an appropriate level of intellectual development completed general and cardiac-specific validated surveys (Pediatric Quality of Life Inventory 4.0 and Pediatric Quality of Life Inventory 3.0, respectively). Demographic and clinical information was collected to grade disease severity. Twenty-five children were enrolled, yielding 25 parent reports and 15 patient self-reports. The PAH group had significantly lower scores than healthy children in all domains. Patients with World Health Organization Functional Class I had significantly higher parent proxy scores in School Functioning (P = .029) and in Heart Problems and Symptoms domain (P = .014) Patients with tricuspid annular plane systolic excursion below -2 z score showed impairment in each parent proxy general domain and in the Cognitive Problems score of the Cardiac module (P = .006). In conclusion the QOL of patients with PAH was impaired in every domain compared with healthy children. Patients with reduced right ventricle systolic function showed significantly lower QOL in all core domains. These results point to the need for psychosocial rehabilitation in addition to somatic care to improve the QOL in this severely ill population.

Prognostic Value of Early Risk Stratification in Pediatric Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a life-threatening disease with risk stratification-based treatment strategy in adults. Although the risk factors have been studied individually in children, effective risk stratification is still lacking. We have tested the prognostic accuracy of pediatric PAH risk factors in our patient group. PATIENTS AND METHODS: Records of 58 PAH patients treated between 1995 and 2019 were reviewed retrospectively. Median age at diagnosis was 4.2 years (range, 0.1-16.1 years), and follow-up was 5.4 years (range, 0.01-24.1 years). Data collected at diagnosis were demographics, World Health Organization functional class, evidence of right ventricular failure, and parameters of echocardiography and cardiac catheterization. RESULTS: Mortality was 29% and 33% reached the composite endpoint. Patients with idiopathic PAH (n = 12) had increased risk of mortality compared with the congenital heart disease-associated PAH group (n = 32) (P = .0024). Neither the initial World Health Organization functional class staging nor the echocardiographic parameters significantly predicted the prognosis. The number of risk factors had no significant prognostic value either. In contrast, patients with higher pulmonary vascular resistance index (PVRI) had significantly increased risk (each 10 Wood units ⋅ m2 increase in PVRI being associated with 49.1% higher hazard, P = .0048). CONCLUSIONS: Survival analysis showed that PAH etiology might be an important determinant in pediatric PAH risk stratification. We confirmed that PVRI has predictive value in prognostic assessment. We could not establish the prognostic value of nonweighted single risk factors or their combination to predict pediatric PAH outcome due to the low sample size, but these results indicate that such studies are warranted.