Ultra-high-resolution CT vs. invasive angiography for detecting hemodynamically significant coronary artery disease: Rationale and methods of the CORE-PRECISION multicenter study.

BACKGROUND: Direct coronary arterial evaluation via computed tomography (CT) angiography is the most accurate noninvasive test for the diagnosis of coronary artery disease (CAD). However, diagnostic accuracy is limited in the setting of severe coronary calcification or stents. Ultra-high-resolution CT (UHR-CT) may overcome this limitation, but no rigorous study has tested this hypothesis. METHODS: The CORE-PRECISION is an international, multicenter, prospective diagnostic accuracy study testing the non-inferiority of UHR-CT compared to invasive coronary angiography (ICA) for identifying patients with hemodynamically significant CAD. The study will enroll 150 patients with history of CAD, defined as prior documentation of lumen obstruction, stenting, or a calcium score ≥400, who will undergo UHR-CT before clinically prompted ICA. Assessment of hemodynamically significant CAD by UHR-CT and ICA will follow clinical standards. The reference standard will be the quantitative flow ratio (QFR) with <0.8 defined as abnormal. All data will be analyzed in independent core laboratories. RESULTS: The primary outcome will be the comparative diagnostic accuracy of UHR-CT vs. ICA for detecting hemodynamically significant CAD on a patient level. Secondary analyses will focus on vessel level diagnostic accuracy, quantitative stenosis analysis, automated contour detection, in-depth plaque analysis, and others. CONCLUSION: CORE-PRECISION aims to investigate if UHR-CT is non-inferior to ICA for detecting hemodynamically significant CAD in high-risk patients, including those with severe coronary calcification or stents. We anticipate this study to provide valuable insights into the utility of UHR-CT in this challenging population and for its potential to establish a new standard for CAD assessment.

Psychotropic Medication Usage in Pediatric CKD: Reporting from the Chronic Kidney Disease in Children Cohort.

BACKGROUND: Mental health disorders (MHD) within the pediatric chronic kidney disease (CKD) population are prevalent. The frequency is unknown with which psychotropic medications that commonly treat these conditions are used in this population. METHODS: Data from the Chronic Kidney Disease in Children (CKiD) cohort study were utilized to describe the use of psychotropic medications and patient-related characteristics of use. Medications were classified into 3 groups: antidepressants, CNS stimulants, and antipsychotic/mood stabilizing medications. Participant age, sex, CKD severity, and duration of medication use were ascertained. Medication use was evaluated in parallel with CKD disease type, presence of urological comorbidity, and hypertension. Chi-square tests compared subgroup medication use. RESULTS: Among 1074 CKiD participants (median baseline age 9.8 years), 6% (n=60) of participants used psychotropic medications at study entry with 11% reporting incident use of any medication category (n=120). CNS stimulants were most common at baseline. Antidepressants were more frequent among incident users at 7%. Use of two or more medications was rare (3%). Median eGFR at medication initiation was 45 ml/min|1.73m2. CNS stimulants were reported at a higher rate in males compared to females (p<0.05). CONCLUSIONS: 11% of CKiD patients report incident use of any psychotropic medication, with 7% reporting incident use of antidepressants. Future work is warranted to better ascertain the frequency, safety, and efficacy of psychotropic medication usage in relationship to formal MHD diagnoses in the pediatric CKD population.

Pubertal luteinizing hormone levels in children with chronic kidney disease and association with change in glomerular filtration rate.

BACKGROUND: Children with chronic kidney disease (CKD) are at risk for abnormalities in pubertal development. We aimed to describe the timing of pubertal onset by luteinizing hormone (LH) levels and the association between hormonal onset of puberty with changes in GFR. METHODS: Data from the Chronic Kidney Disease in Children (CKiD) study were collected prospectively. GFR was estimated at annual visits and measured by iohexol clearance every other year. LH was measured from stored repository serum samples in a nested sample of 124 participants. Hormonal onset of puberty was defined as LH level greater than or equal to 0.3 IU/L. A mixed effects model with random intercepts and slopes was used to compare the slope of decline of GFR before and after hormonal onset of puberty. The model was adjusted for age, glomerular disease diagnosis, baseline proteinuria on the log scale, and BMI. RESULTS: Median age at hormonal onset of puberty was 9.9 years (IQR 8.1, 11.9) in girls and 10.2 years (IQR 9.2, 11.0) in boys. The mixed effects model showed faster decline in both estimated GFR and measured GFR in boys after hormonal onset of puberty (p < 0.001), and a similar but attenuated accelerated estimated GFR decline was observed for girls with no difference for measured GFR. CONCLUSIONS: LH levels in the post-pubertal range were observed prior to clinical manifestations of puberty in children with CKD. Hormonal onset of puberty was associated with faster decline in GFR, particularly among boys with CKD.

Circulating Metabolomic Associations with Neurocognitive Outcomes in Pediatric CKD.

BACKGROUND: Children with CKD are at risk for impaired neurocognitive functioning. We investigated metabolomic associations with neurocognition in children with CKD. METHODS: We leveraged data from the Chronic Kidney Disease in Children (CKiD) study and the Neurocognitive Assessment and Magnetic Resonance Imaging Analysis of Children and Young Adults with Chronic Kidney Disease (NiCK) study. CKiD is a multi-institutional cohort that enrolled children aged 6 months to 16 years with eGFR 30-90 ml/min per 1.73 m 2 ( n =569). NiCK is a single-center cross-sectional study of participants aged 8-25 years with eGFR<90 ml/min per 1.73 m 2 ( n =60) and matched healthy controls ( n =67). Untargeted metabolomic quantification was performed on plasma (CKiD, 622 metabolites) and serum (NiCK, 825 metabolites) samples. Four neurocognitive domains were assessed: intelligence, attention regulation, working memory, and parent ratings of executive function. Repeat assessments were performed in CKiD at 2-year intervals. Linear regression and linear mixed-effects regression analyses adjusting for age, sex, delivery history, hypertension, proteinuria, CKD duration, and glomerular versus nonglomerular diagnosis were used to identify metabolites associated with neurocognitive z-scores. Analyses were performed with and without adjustment for eGFR. RESULTS: There were multiple metabolite associations with neurocognition observed in at least two of the analytic samples (CKiD baseline, CKiD follow-up, and NiCK CKD). Most of these metabolites were significantly elevated in children with CKD compared with healthy controls in NiCK. Notable signals included associations with parental ratings of executive function: phenylacetylglutamine, indoleacetylglutamine, and trimethylamine N-oxide-and with intelligence: γ -glutamyl amino acids and aconitate. CONCLUSIONS: Several metabolites were associated with neurocognitive dysfunction in pediatric CKD, implicating gut microbiome-derived substances, mitochondrial dysfunction, and altered energy metabolism, circulating toxins, and redox homeostasis.

Combined Computed Tomography Angiography-Computed Tomography Perfusion in the Identification and Prognostic Assessment of Myocardial Bridging from the CORE320 Study: 5-Year Follow-Up.

Our objective is to use computed tomography angiography (CTA) and computed tomography perfusion (CTP) to identify the ischemic significance of myocardial bridging (MB). We also seek to determine the long-term prognostication of MB in the presence or absence of obstructive coronary artery disease (CAD). The CORE320, a prospective, multicenter study including 381 patients with known or suspected CAD clinically referred for invasive coronary angiography who underwent combined (CTA-CTP) and single-photon emission computed tomography before conventional coronary angiography. The incidence of MB was identified in 135 patients (35.4%) with 93.9% identified in the left anterior descending artery. MB were divided as partially encased versus fully encased. There was no difference in ischemia identified between partially encased MB and fully encased MB (37 [40%] vs 25 [35%], p = 0.54]. Ischemia was identified at similar rates in partially versus fully encased MB by single-photon emission computed tomography at (8 [9%] vs 8 [11%], p = 0.57] and CTP (34 [37%] vs 21 [30%], p = 0.33]. There was no difference in the primary outcome of 5-year outcome of combined incidence of myocardial infarction or death. The restricted mean survival time in patients with CTA with <50% stenosis with or without a MB was 4.906 years (95% confidence interval 4.759 to 5.000) and 4.891 years (95% confidence interval 4.718 to 5.000), respectively (p = 0.824). Cardiac computed tomography perfusion imaging can assess both anatomic and functional significance of myocardial bridging with diagnostic accuracy similar to current standard imaging. Furthermore, 5-year cardiovascular events were not different with the presence of MB in both obstructive and non-obstructive CAD.

Coronary artery disease grading by cardiac CT for predicting outcome in patients with stable angina.

BACKGROUND: The coronary atheroma burden drives major adverse cardiovascular events (MACE) in patients with suspected coronary heart disease (CHD). However, a consensus on how to grade disease burden for effective risk stratification is lacking. The purpose of this study was to compare the effectiveness of common CHD grading tools to risk stratify symptomatic patients. METHODS: We analyzed the 5-year outcome of 381 prospectively enrolled patients in the CORE320 international, multicenter study using baseline clinical and cardiac computer-tomography (CT) imaging characteristics, including coronary artery calcium score (CACS), percent atheroma volume, "high-risk" plaque, disease severity grading using the CAD-RADS, and two simplified CAD staging systems. We applied Cox proportional hazard models and area under the curve (AUC) analysis to predict MACE or hard MACE, defined as death, myocardial infarction, or stroke. Analyses were stratified by a history of CHD. Additional forward selection analysis was performed to evaluate incremental value of metrics. RESULTS: Clinical characteristics were the strongest predictors of MACE in the overall cohort. In patients without history of CHD, CACS remained the only independent predictor of MACE yielding an AUC of 73 (CI 67-79) vs. 64 (CI 57-70) for clinical characteristics. Noncalcified plaque volume did not add prognostic value. Simple CHD grading schemes yielded similar risk stratification as the CAD-RADS classification. Forward selection analysis confirmed prominent role of CACS and revealed usefulness of functional testing in subgroup with known CHD. CONCLUSION: In patients referred for invasive angiography, a history of CHD was the strongest predictor of MACE. In patients without history of CHD, a coronary calcium score yielded at least equal risk stratification vs. more complex CHD grading.

Longitudinal changes of health-related quality of life in childhood chronic kidney disease.

BACKGROUND: Few longitudinal studies have evaluated the impact of chronic kidney disease (CKD) duration on health-related quality of life (HRQOL). The study's aim was to determine how HRQOL changes over time in childhood CKD. METHODS: Study participants were children in the chronic kidney disease in children (CKiD) cohort who completed the pediatric quality of life inventory (PedsQL) on three or more occasions over the course of two or more years. Generalized gamma (GG) mixed-effects models were applied to assess the effect of CKD duration on HRQOL while controlling for selected covariates. RESULTS: A total of 692 children (median age = 11.2) with a median of 8.3 years duration of CKD were evaluated. All subjects had a GFR greater than 15 ml/min/1.73 m2. GG models with child self-report PedsQL data indicated that longer CKD duration was associated with improved total HRQOL and the 4 domains of HRQOL. GG models with parent-proxy PedsQL data indicated that longer duration was associated with better emotional but worse school HRQOL. Increasing trajectories of child self-report HRQOL were observed in the majority of subjects, while parents less frequently reported increasing trajectories of HRQOL. There was no significant relationship between total HRQOL and time-varying GFR. CONCLUSIONS: Longer duration of the disease is associated with improved HRQOL on child self-report scales; however, parent-proxy results were less likely to demonstrate any significant change over time. This divergence could be due to greater optimism and accommodation of CKD in children. Clinicians can use these data to better understand the needs of pediatric CKD patients. A higher resolution version of the Graphical abstract is available as Supplementary information.

Development of an adaptive clinical web-based prediction tool for kidney replacement therapy in children with chronic kidney disease.

Clinicians need improved prediction models to estimate time to kidney replacement therapy (KRT) for children with chronic kidney disease (CKD). Here, we aimed to develop and validate a prediction tool based on common clinical variables for time to KRT in children using statistical learning methods and design a corresponding online calculator for clinical use. Among 890 children with CKD in the Chronic Kidney Disease in Children (CKiD) study, 172 variables related to sociodemographics, kidney/cardiovascular health, and therapy use, including longitudinal changes over one year were evaluated as candidate predictors in a random survival forest for time to KRT. An elementary model was specified with diagnosis, estimated glomerular filtration rate and proteinuria as predictors and then random survival forest identified nine additional candidate predictors for further evaluation. Best subset selection using these nine additional candidate predictors yielded an enriched model additionally based on blood pressure, change in estimated glomerular filtration rate over one year, anemia, albumin, chloride and bicarbonate. Four additional partially enriched models were constructed for clinical situations with incomplete data. Models performed well in cross-validation, and the elementary model was then externally validated using data from a European pediatric CKD cohort. A corresponding user-friendly online tool was developed for clinicians. Thus, our clinical prediction tool for time to KRT in children was developed in a large, representative pediatric CKD cohort with an exhaustive evaluation of potential predictors and supervised statistical learning methods. While our models performed well internally and externally, further external validation of enriched models is needed.

Association of clinical characteristics with urine uromodulin in children with chronic kidney disease.

BACKGROUND: Uromodulin is the most abundant protein in the urine of healthy adults, and higher urine concentrations mark better tubular health. Greater kidney size and function are predictors of higher uromodulin levels in adults. Urine uromodulin has not yet been studied in children with chronic kidney disease (CKD). Thus, we sought to determine the relationship between age and kidney function with urine uromodulin levels in children with CKD. METHODS: In the CKD in Children (CKiD) cohort, we utilized multivariable linear regression to evaluate the relationship of age and eGFR with urine uromodulin levels. The primary outcome was uromodulin indexed to urine creatinine (Umod/Cr, mg/g), which was log2-transformed given its skewed distribution. RESULTS: Among 677 CKiD participants, the median age was 11.8 years (8.2-15.3), the median eGFR was 49 ml/min/1.73 m2 (37-63), the etiology of CKD was glomerular disease in 31%, and the median Umod/Cr level was 0.114 mg/g (0.045-0.226). In the multivariable models, each one-year older age was associated with 0.18 (12%) lower log2(Umod/Cr) and 0.20 (13%) lower log2(Umod/Cr) among those with non-glomerular and glomerular disease, respectively (p < 0.001). However, we did not find a statistically significant association between eGFR and Umod/Cr in either participants with non-glomerular or glomerular disease (p = 0.13 and p = 0.58, respectively). CONCLUSIONS: Among children with CKD, older age is significantly associated with lower Umod/Cr, independent of eGFR. Further studies are needed to comprehensively evaluate age-specific reference ranges for urine uromodulin and to evaluate the longitudinal relationship of uromodulin with both age and eGFR in children with CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Predicting Significant Coronary Obstruction in a Population with Suspected Coronary Disease and Absence of Coronary Calcium: CORE-64 / CORE320 Studies. / Predição de Obstrução Coronariana Significativa em População com Suspeita de Doença Coronariana e Ausência de Cálcio Coronariano: CORE-64 e CORE320.

BACKGROUND: Coronary artery calcium (CAC) scanning can be performed using non-contrast computed tomography to predict cardiovascular events, but has less value for risk stratification in symptomatic patients. OBJECTIVE: To identify and validate predictors of significant coronary obstruction (SCO) in symptomatic patients without coronary artery calcification. METHODS: A total of 4,258 participants were screened from the CORE64 and CORE320 studies that enrolled patients referred for invasive angiography, and from the Quanta Registry that included patients referred for coronary computed tomography angiography (CTA). Logistic regression models evaluated associations between cardiovascular risk factors, CAC, and SCO. An algorithm to assess the risk of SCO was proposed for patients without CAC. Significance level of 5% was used in the analyses. RESULTS: Of the 509 participants of the CORE study, 117 (23%) had zero coronary calcium score; 13 (11%) patients without CAC had SCO. Zero calcium score was related to younger age, female gender, lower body mass index, no diabetes, and no dyslipidemia. Being a current smoker increased ~3.5 fold the probability of SCO and other CV risk factors were not significantly associated. Considering the clinical findings, an algorithm to further stratify zero calcium score patients was proposed and had a limited performance in the validation cohort (AUC 58; 95%CI 43, 72). CONCLUSION: A lower cardiovascular risk profile is associated with zero calcium score in a setting of high-risk patients. Smoking is the strongest predictor of SCO in patients without CAC.

FUNDAMENTO: A avaliação do Escore de Cálcio Coronariano (ECC) pode ser realizada por tomografia computadorizada sem contraste para prever eventos cardiovasculares, mas tem menor valor na estratificação de risco em pacientes sintomáticos. OBJETIVO: Identificar e validar preditores de obstrução coronariana significativa (OCS) em pacientes sintomáticos sem calcificação da artéria coronária. MÉTODOS: Um total de 4258 participantes foram rastreados dos estudos CORE64 e CORE 320, nos quais foram avaliados pacientes encaminhados para angiografia invasiva, e do Quanta Registry que incluiu pacientes encaminhados para angiotomografia. Modelos de regressão logística avaliaram associações entre fatores de risco cardiovascular, ECC e OCS. Um nível de significância de 5% foi usado nas análises. RESULTADOS: Dos 509 participantes do estudo CORE, 117 (23%) apresentaram um ECC igual a zero; 13 (11%) pacientes sem cálcio coronariano apresentaram OCS. A ausência de cálcio coronariano correlacionou-se com idade mais jovem, sexo feminino, índice de massa corporal mais baixo, ausência de diabetes, e ausência de dislipidemia. O fato de ser fumante atual aumentou em 3,5 vezes a probabilidade de OCS e outros fatores de risco cardiovasculares não apresentaram associação significativa. Considerando os achados clínicos, um algoritmo para estratificar os pacientes com ECC igual a zero foi proposto, e tiveram desempenho limitado na coorte de validação (AUC 58; IC95% 43, 72). CONCLUSÃO: Um perfil de risco cardiovascular mais baixo está associado a um ECC igual a zero em pacientes de alto risco. Tabagismo é o preditor mais forte de OCS em pacientes com ausência de cálcio coronariano.

A longitudinal analysis of the effect of anemia on executive functions in children with mild to moderate chronic kidney disease.

BACKGROUND: Children with chronic kidney disease (CKD) are at risk for cognitive dysfunction. The aim of this study was to investigate associations between executive functions (EF), anemia, and iron deficiency. METHODS: A total of 688 children > 6 years of age enrolled in the Chronic Kidney Disease in Children (CKiD) study who underwent evaluation for EF were included. Hemoglobin (Hgb) was characterized as low (1st-5th percentile) or very low (< 1st percentile) compared to normative values for age, sex, and race irrespective of erythropoiesis-stimulating agent (ESA) usage. Longitudinal analysis was conducted using consecutive visit pairs, with anemia status defined as new onset, resolved, or persistent. Linear mixed models with random intercept were used and adjusted for key covariates. RESULTS: Anemia was present in 41% of children, and median Hgb was 11.8 gm/dl. New onset anemia was associated with lower digit span total score (- 0.75, 95% CI - 1.36, - 0.15, p = 0.01). Persistent anemia was associated with lower scores on color-word inhibition/switching (ß = - 0.98; 95% CI - 1.78, - 0.18, p = 0.02). Errors of omission were significantly higher (worse) in those with persistent anemia (ß = 2.67, 95% CI 0.18, 5.17, p = 0.04). Very low Hgb levels were significantly associated with lower color-word inhibition/switching scores (ß = - 1.33, 95% CI - 2.16, - 0.51; p = 0.002). Anemia and low GFR were associated with lower category fluency scores compared to non-anemic subjects with higher GFR (ß = - 1.09, 95% CI - 2.09, - 0.10, p = 0.03). CONCLUSIONS: The presence of anemia, in addition to its severity and duration in children with CKD, is associated with poorer scores on select measures of EF. A higher resolution version of the Graphical abstract is available as Supplementary information.

Predição de Obstrução Coronariana Significativa em População com Suspeita de Doença Coronariana e Ausência de Cálcio Coronariano: CORE-64 e CORE320 / Predicting Significant Coronary Obstruction in a Population with Suspected Coronary Disease and Absence of Coronary Calcium: CORE-64 / CORE320 Studies

Resumo Fundamento A avaliação do Escore de Cálcio Coronariano (ECC) pode ser realizada por tomografia computadorizada sem contraste para prever eventos cardiovasculares, mas tem menor valor na estratificação de risco em pacientes sintomáticos. Objetivo Identificar e validar preditores de obstrução coronariana significativa (OCS) em pacientes sintomáticos sem calcificação da artéria coronária. Métodos Um total de 4258 participantes foram rastreados dos estudos CORE64 e CORE 320, nos quais foram avaliados pacientes encaminhados para angiografia invasiva, e do Quanta Registry que incluiu pacientes encaminhados para angiotomografia. Modelos de regressão logística avaliaram associações entre fatores de risco cardiovascular, ECC e OCS. Um nível de significância de 5% foi usado nas análises. Resultados Dos 509 participantes do estudo CORE, 117 (23%) apresentaram um ECC igual a zero; 13 (11%) pacientes sem cálcio coronariano apresentaram OCS. A ausência de cálcio coronariano correlacionou-se com idade mais jovem, sexo feminino, índice de massa corporal mais baixo, ausência de diabetes, e ausência de dislipidemia. O fato de ser fumante atual aumentou em 3,5 vezes a probabilidade de OCS e outros fatores de risco cardiovasculares não apresentaram associação significativa. Considerando os achados clínicos, um algoritmo para estratificar os pacientes com ECC igual a zero foi proposto, e tiveram desempenho limitado na coorte de validação (AUC 58; IC95% 43, 72). Conclusão Um perfil de risco cardiovascular mais baixo está associado a um ECC igual a zero em pacientes de alto risco. Tabagismo é o preditor mais forte de OCS em pacientes com ausência de cálcio coronariano.

Abstract Background Coronary artery calcium (CAC) scanning can be performed using non-contrast computed tomography to predict cardiovascular events, but has less value for risk stratification in symptomatic patients. Objective To identify and validate predictors of significant coronary obstruction (SCO) in symptomatic patients without coronary artery calcification. Methods A total of 4,258 participants were screened from the CORE64 and CORE320 studies that enrolled patients referred for invasive angiography, and from the Quanta Registry that included patients referred for coronary computed tomography angiography (CTA). Logistic regression models evaluated associations between cardiovascular risk factors, CAC, and SCO. An algorithm to assess the risk of SCO was proposed for patients without CAC. Significance level of 5% was used in the analyses. Results Of the 509 participants of the CORE study, 117 (23%) had zero coronary calcium score; 13 (11%) patients without CAC had SCO. Zero calcium score was related to younger age, female gender, lower body mass index, no diabetes, and no dyslipidemia. Being a current smoker increased ~3.5 fold the probability of SCO and other CV risk factors were not significantly associated. Considering the clinical findings, an algorithm to further stratify zero calcium score patients was proposed and had a limited performance in the validation cohort (AUC 58; 95%CI 43, 72). Conclusion A lower cardiovascular risk profile is associated with zero calcium score in a setting of high-risk patients. Smoking is the strongest predictor of SCO in patients without CAC.

Cardiovascular Risk Prediction Using Machine Learning in a Large Japanese Cohort.

Background: Cardiovascular disease (CVD) screening entails precise event prediction to orient risk stratification, resource allocation, and insurance policy. We used random survival forests (RSF) to identify markers of incident CVD among Japanese adults enrolled in an employer-mandated screening program. Methods and Results: We examined biomarker, health history, medication use, and lifestyle data from 155,108 adults aged ≥40 years. The occurrence of coronary artery disease (CAD) or atherosclerotic CVD (ASCVD) events was examined over 6 years of follow-up. The analysis used RSF to identify predictors, then investigated simplified RSF models with fewer predictors for individual-level risk prediction. Data were split into training (70%) and test (30%) datasets. At baseline, the median patient age was 47 years (interquartile range 41-56 years), with 65% males. In all, 1,642 CAD and 2,164 ASCVD events were observed. RSF identified history of heart disease, age, self-reported blood pressure medication, HbA1c, fasting blood sugar, and high-density lipoprotein as important markers of both endpoints. RSF analyses with only the top 20 predictors demonstrated good performance, with areas under the curve of >84% for CAD and >82% for ASCVD in test data across 6 years. Conclusions: We present a machine learning technique for accurate assessment of cardiovascular risk using employer-mandated annual health checkup information. The algorithm produces individual-level risk curves over time, empowering clinicians to efficiently implement prevention strategies in a low-risk population.

Urine Uromodulin Is Not Associated With Blood Pressure in the Chronic Kidney Disease in Children Cohort.

BACKGROUND: Uromodulin regulates activity of the sodium-potassium-two-chloride transporter in the loop of Henle. In adults, higher urine uromodulin levels are associated with greater rise in blood pressure (BP) in response to salt intake. We hypothesized that higher urine uromodulin levels would be associated with higher BP in children with chronic kidney disease, and that there would be an interaction of dietary sodium on this association. METHODS: In the chronic kidney disease in children Cohort, we utilized univariable and multivariable linear regression models to evaluate the relationship between baseline spot urine uromodulin levels indexed to urine creatinine (Umod/Cr mg/g) and 24-hour mean systolic and diastolic BP, as well as baseline clinic BP. We also tested whether sodium intake (g/day) modified these relationships. RESULTS: Among 436 participants, the median age was 12.4 years (8.9-15.2), median estimated glomerular filtration rate was 50 mL/min per 1.73 m2 (36-62), and median 24-hour mean systolic BP was 112 mm Hg (104-119). The etiology of chronic kidney disease was glomerular disease in 27%. In univariable models, each 2-fold higher Umod/Cr ratio was associated with a 1.66 mm Hg (95% CI, -2.31 to -1.00) lower 24-hour mean systolic and a 1.71 mm Hg (-2.45 to -0.97) lower clinic systolic BP. However, there was no statistically significant association between Umod/Cr and either 24-hour or clinic BP in multivariable models. We did not find a significant interaction between uromodulin and sodium intake in their effect on BP (P>0.05 in all models). CONCLUSIONS: Urine uromodulin levels are not associated with BP in the chronic kidney disease in children cohort. Further studies are needed to confirm this finding in healthy pediatric cohorts.

Perivascular fat attenuation for predicting adverse cardiac events in stable patients undergoing invasive coronary angiography.

BACKGROUND: Inflammation surrounding the coronary arteries can be non-invasively assessed using pericoronary adipose tissue attenuation (PCAT). While PCAT holds promise for further risk stratification of patients with low coronary artery disease (CAD) prevalence, its value in higher risk populations remains unknown. METHODS: CORE320 enrolled patients referred for invasive coronary angiography with known or suspected CAD. Coronary computed tomography angiography (CCTA) images were collected for 381 patients for whom clinical outcomes were assessed 5 years after enrollment. Using semi-automated image analysis software, PCAT was obtained and normalized for the right coronary (RCA), left anterior descending (LAD), and left circumflex arteries (LCx). The association between PCAT and major adverse cardiovascular events (MACE) during follow up was assessed using Cox regression models. RESULTS: Thirty-seven patients were excluded due to technical failure. For the remaining 344 patients, median age was 62 (interquartile range, 55-68) with 59% having ≥1 coronary artery stenosis of ≥50% by quantitative coronary angiography. Mean attenuation values for PCAT in RCA, LAD, and LCx were -74.9, -74.2, and -71.2, respectively. Hazard ratios and 95% confidence intervals (CI) for normalized PCAT in the RCA, LAD, and LCx for MACE were 0.96 (CI: 0.75-1.22, p â€‹= â€‹0.71), 1.31 (95% CI: 0.96-1.78, p â€‹= â€‹0.09), and 0.98 (95% CI: 0.78-1.22, p â€‹= â€‹0.84), respectively. For death, stroke, or myocardial infarction only, hazard ratios were 0.68 (0.44-1.07), 0.85 (0.56-1.29), and 0.57 (0.41-0.80), respectively. CONCLUSIONS: In patients referred for invasive coronary angiography with suspected CAD, PCAT did not predict MACE during long term follow up. Further studies are needed to understand the relationship of PCAT with CAD risk.

The Relationship Between Neighborhood Disadvantage and Kidney Disease Progression in the Chronic Kidney Disease in Children (CKiD) Cohort.

RATIONALE & OBJECTIVE: To examine the relationship between neighborhood poverty and deprivation, chronic kidney disease (CKD) comorbidities, and disease progression in children with CKD. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: Children with mild to moderate CKD enrolled in the CKiD (Chronic Kidney Disease in Children) study with available US Census data. EXPOSURE: Neighborhood poverty and neighborhood disadvantage. OUTCOME: Binary outcomes of short stature, obesity, hypertension, and health care utilization for cross-sectional analysis; a CKD progression end point (incident kidney replacement therapy [KRT] or 50% loss in estimated glomerular filtration rate), and mode of first KRT for time-to-event analysis. ANALYTICAL APPROACH: Cross-sectional analysis of health characteristics at time of first Census data collection using logistic regression to estimate odds ratios. Risk for CKD progression was analyzed using a Cox proportional hazard model. Multivariable models were adjusted for race, ethnicity, sex, and family income. RESULTS: There was strong agreement between family and neighborhood socioeconomic characteristics. Risk for short stature, hospitalization, and emergency department (ED) use were significantly associated with lower neighborhood income. After controlling for race, ethnicity, sex, and family income, the odds of hospitalization (OR, 1.71 [95% CI, 1.08-2.71]) and ED use (OR, 1.56 [95% CI, 1.02-2.40]) remained higher for those with lower neighborhood income. The hazard ratio of reaching the CKD progression outcome for participants living in lower income neighborhoods was significantly increased in the unadjusted model only (1.38 [95% CI, 1.02-1.87]). Likelihood of undergoing a preemptive transplant was decreased with lower neighborhood income (OR, 0.47 [95% CI, 0.24-0.96]) and higher neighborhood deprivation (OR, 0.31 [95% CI, 0.10-0.97]), but these associations did not persist after controlling for participant characteristics. LIMITATIONS: Limited generalizability, as only those with consistent longitudinal nephrology care were studied. CONCLUSIONS: Neighborhood-level socioeconomic status (SES) was associated with poorer health characteristics and CKD progression in univariable analysis. However, the relationships were attenuated after accounting for participant-level factors including race. A persistent association of neighborhood poverty with hospitalizations and ED suggests an independent effect of SES on health care utilization, the causes for which deserve additional study.

Overview of the findings and advances in the neurocognitive and psychosocial functioning of mild to moderate pediatric CKD: perspectives from the Chronic Kidney Disease in Children (CKiD) cohort study.

The Chronic Kidney Disease in Children (CKiD) prospective cohort study was designed to address the neurocognitive, growth, cardiovascular, and disease progression of children and adolescents with mild to moderate CKD. The study has had continuous funding from NIDDK for 17 years and has contributed significant advances in pediatric CKD. The goals of this educational review are threefold: (1) to provide an overview of the neurocognitive and psychosocial studies from CKiD to date; (2) to provide best practice recommendations for those working with the neurocognitive and psychosocial aspects of pediatric CKD based on CKiD findings; and (3) to help chart future goals and directives for both research and clinical practice. This collection of 22 empirical studies has produced a number of key findings for children and adolescents with mild to moderate CKD. While various studies suggest a relatively positive presentation for this population as a whole, without evidence of significant impairment or deterioration, findings do indicate the presence of neurocognitive dysfunction, emotional-behavioral difficulties, and lower quality of life for many children with CKD. These findings support the promotion of best practices that are accompanied by additional future clinical and research initiatives with this patient population.

Low variability of plant protein intake in the CKiD cohort does not demonstrate changes in estimated GFR nor electrolyte balance.

BACKGROUND: Vegetable or plant-based sources of protein may confer health benefits in children with progressive kidney disease. Our aims were to understand the effect of the proportion of vegetable protein intake on changes in estimated GFR and to understand the effect of the proportion of vegetable protein intake on serum levels of bicarbonate, phosphorus, and potassium. METHODS: Children with baseline eGFR between 30 and 90 mL/min/1.73 m2 were recruited from 59 centers across North America as part of the chronic kidney disease in children (CKiD) study. The percentage of dietary vegetable protein (VP%) was gathered from annual Food Frequency Questionnaires. We performed longitudinal linear mixed models to determine the effect of VP% on eGFR and longitudinal logistic mixed models to determine the effect of VP% on electrolyte balance (potassium, phosphorus, bicarbonate). RESULTS: Two thousand visits from 631 subjects. Across all dichotomized groups of children (sex, African American race, Hispanic ethnicity, glomerular etiology of CKD, hypertension, anemia, hyperkalemia, hyperphosphatemia, acidosis, BMI < 95th percentile), the median VP% was 32-35%. The longitudinal mixed model analysis did not show any effect of VP% on eGFR electrolyte (bicarbonate, phosphorus, and potassium) abnormalities (p > 0.1). CONCLUSIONS: A diverse cohort of children with CKD has a narrow and homogeneous intake of vegetable protein. Due to the low variability of plant-based protein in the cohort, there were no associations between the percentage of plant protein intake and changes in eGFR nor electrolyte balance. A higher resolution version of the Graphical abstract is available as Supplementary information.