A randomized controlled trial to assess the impact of psychoeducation on the quality of life of parents with children with congenital heart defects-Quantitative component.

PURPOSE: To develop, implement and assess the results of psychoeducation to improve the QoL of parents with CHD newborns. METHODS: Participants were parents of inpatient newborns with the diagnosis of non-syndromic CHD. We conducted a parallel RCT with an allocation ratio of 1:1 (intervention vs. control), considering the newborns, using mixed methods research. The intervention group received psychoeducation (Parental Psychoeducation in CHD [PPeCHD]) and the usual routines, and the control group received just the regular practices. The allocation concealment was assured. PI was involved in enrolling participants, developing and implementing the intervention, data collection and data analysis. We followed the Consolidated Standards of Reporting Trials (CONSORT) guidelines. RESULTS: Parents of eight newborns were allocated to the intervention group (n = 15 parents) and eight to the control group (n = 13 parents). It was performed as an intention-to-treat (ITT) analysis. In M2 (4 weeks), the intervention group presented better QoL levels in the physical, psychological, and environmental domains of World Health Organization Quality of Life instrument (WHOQOL-Bref). In M3 (16 weeks), scores in physical and psychological domains maintained a statistically significant difference between the groups. CONCLUSIONS: The PPeCHD, the psychoeducational intervention we developed, positively impacted parental QoL. These results support the initial hypothesis. This study is a fundamental milestone in this research field, adding new essential information to the literature.

Cardiovascular rhythmicity in overweight and obese children / Ritmicidade cardiovascular em crianças com sobrepeso e obesidade

Abstract Introduction: Obesity is thought to play a role in the disruption of cardiac rhythmicity in obese children, but this is mostly an unexplored field of investigation. We aimed to evaluate the impact of overweight and obesity on circadian and ultradian cardiovascular rhythmicity of prepubertal children, in comparison with normal weight counterparts. Methods: We performed a cross sectional study of 316 children, followed in the birth cohort Generation XXI (Portugal). Anthropometrics and 24-hour ambulatory blood pressure were measured and profiles were examined with Fourier analysis for circadian and ultradian blood pressure (BP) and heart rate (HR) rhythms. Results: Overweight/obese children presented more frequently a non-dipping BP pattern than normal weight counterparts (31.5% vs. 21.6%, p = 0.047). The prevalence of 24-hour mean arterial pressure (MAP) and 8-hour HR rhythmicity was significantly lower in obese children (79.3% vs. 88.0%, p = 0.038 and 33.3% vs. 45.2%, p = 0.031, respectively). The prevalence of the remaining MAP and HR rhythmicity was similar in both groups. No differences were found in the median values of amplitudes and acrophases of MAP and HR rhythms. Discussion: The alterations found in rhythmicity suggest that circadian and ultradian rhythmicity analysis might be sensitive in detecting early cardiovascular dysregulations, but future studies are needed to reinforce our findings and to better understand their long-term implications.

Resumo Introdução: Acredita-se que a obesidade desempenhe um papel na desregulação da ritmicidade cardíaca em crianças obesas, mas esse é um campo de investigação ainda pouco explorado. O objetivo deste trabalho foi avaliar o impacto do sobrepeso e da obesidade na ritmicidade cardiovascular circadiana e ultradiana de crianças pré-púberes, em comparação com crianças com peso normal. Métodos: Realizamos um estudo transversal com 316 crianças, acompanhadas na coorte de nascimentos Geração XXI (Portugal). Foram medidos dados antropométricos e a pressão arterial ambulatorial de 24 horas, e os perfis foram examinados com uma análise de Fourier para ritmos circadianos e ultradianos de pressão arterial (PA) e frequência cardíaca (FC). Resultados: Crianças com sobrepeso/obesidade apresentaram mais frequentemente um padrão de PA não-dipper em comparação com crianças com peso normal (31,5% vs. 21,6%; p = 0,047). A prevalência da pressão arterial média (PAM) de 24 horas e da ritmicidade da FC de 8 horas foi significativamente menor em crianças obesas (79,3% vs. 88,0%; p = 0,038 e 33,3% vs. 45,2%; p = 0,031, respectivamente). A prevalência das restantes ritmicidades da PAM e da FC foi semelhante em ambos os grupos. Não foram encontradas diferenças nos valores medianos das amplitudes e acrofases dos ritmos de PAM e FC. Discussão: As alterações encontradas na ritmicidade sugerem que a análise da ritmicidade circadiana e ultradiana pode ser sensível na detecção de desregulações cardiovasculares precoces, mas são necessários novos estudos para reforçar nossos achados e entender melhor suas implicações a longo prazo.

Cardiovascular rhythmicity in overweight and obese children.

INTRODUCTION: Obesity is thought to play a role in the disruption of cardiac rhythmicity in obese children, but this is mostly an unexplored field of investigation. We aimed to evaluate the impact of overweight and obesity on circadian and ultradian cardiovascular rhythmicity of prepubertal children, in comparison with normal weight counterparts. METHODS: We performed a cross sectional study of 316 children, followed in the birth cohort Generation XXI (Portugal). Anthropometrics and 24-hour ambulatory blood pressure were measured and profiles were examined with Fourier analysis for circadian and ultradian blood pressure (BP) and heart rate (HR) rhythms. RESULTS: Overweight/obese children presented more frequently a non-dipping BP pattern than normal weight counterparts (31.5% vs. 21.6%, p = 0.047). The prevalence of 24-hour mean arterial pressure (MAP) and 8-hour HR rhythmicity was significantly lower in obese children (79.3% vs. 88.0%, p = 0.038 and 33.3% vs. 45.2%, p = 0.031, respectively). The prevalence of the remaining MAP and HR rhythmicity was similar in both groups. No differences were found in the median values of amplitudes and acrophases of MAP and HR rhythms. DISCUSSION: The alterations found in rhythmicity suggest that circadian and ultradian rhythmicity analysis might be sensitive in detecting early cardiovascular dysregulations, but future studies are needed to reinforce our findings and to better understand their long-term implications.

Improving the quality of life of parents of patients with congenital abnormalities using psychoeducational interventions: a systematic review.

PURPOSE: To identify psychoeducational interventions that target parents of children with congenital abnormalities (CA) and evaluate their impact on quality of life (QoL). METHODS: The search was conducted in six electronic databases, complemented by references of the studies found, studies of evidence synthesis, a manual search of relevant scientific meetings' abstracts and contact with experts. We included primary studies on parents of children with CA that studied psychoeducational interventions versus standard care. We assessed the risk of bias using Cochrane Collaboration's tool. RESULTS: We included six studies focusing on congenital heart defects (CHD). They described four different psychoeducational strategies. In four studies, statistically significant differences were found. For clinical practice, we considered three interventions as more feasible: the Educational program for mothers, with a group format of four sessions weekly; CHIP-Family intervention, which includes a parental group workshop followed by an individual follow-up booster session; and WeChat educational health program with an online format. CONCLUSIONS: This review is the first that assesses the impact of psychoeducational interventions targeted at parents of children with CA on their QoL. The best approach to intervention is multiple group sessions. Two essential strategies were to give support material, enabling parents to review, and the possibility of an online program application, increasing accessibility. However, because all included studies focus on CHD, generalizations should be made carefully. These findings are crucial to guide future research to promote and improve comprehensive and structured support for families and integrate them into daily practice.

Congenital atrioventricular heart block: From diagnosis to treatment.

Congenital atrioventricular block (CAVB), classified as such when diagnosed in utero, at birth or during the first month of life, is a rare condition with an estimated incidence between 1/15 000 and 1/22 000 live births. It is now accepted that the pathophysiology of this condition is predominantly associated with an immunologically mediated response to the conduction system, which occurs due to transplacental passage of maternal autoantibodies from mothers diagnosed, in most cases, with systemic lupus erythematosus or Sjögren syndrome. Fetal echocardiography continues to be the diagnostic gold standard, however there are other techniques with good results and advantages. Regarding therapeutics, both pharmacological measures and cardiac stimulation techniques have been developed to increase the safety of procedures, decrease associated mortality and morbidity, and provide a better quality of life for patients, although there are disagreements in deciding the best therapeutic plan. This review aims to summarize and elucidate the best diagnostic approach as well as the best therapeutic strategies. A search was performed in the PubMed and Science Direct databases of articles published and accepted for publication. The following search terms were used: "Congenital atrioventricular block", "Neonatal lupus", "Pacemaker", "Pathophysiology", "Electrophysiology", and "Prenatal diagnosis". Articles in Portuguese and English were selected. No time constraints were used. Repeated articles were excluded from the two databases.

Quality of life of parents with children with congenital abnormalities: a systematic review with meta-analysis of assessment methods and levels of quality of life.

PURPOSE: To quantify and understand how to assess the quality of life and health-related QoL of parents with children with congenital abnormalities. METHODS: We conducted a systematic review with meta-analysis. The search was carried out in 5 bibliographic databases and in ClinicalTrials.gov. No restriction on language or date of publication was applied. This was complemented by references of the studies found and studies of evidence synthesis, manual search of abstracts of relevant congresses/scientific meetings and contact with experts. We included primary studies (observational, quasi-experimental and experimental studies) on parents of children with CA reporting the outcome quality of life (primary outcome) of parents, independently of the intervention/exposure studied. RESULTS: We included 75 studies (35 observational non-comparatives, 31 observational comparatives, 4 quasi-experimental and 5 experimental studies). We identified 27 different QoL instruments. The two most frequently used individual QoL instruments were WHOQOL-Bref and SF-36. Relatively to family QoL tools identified, we emphasized PedsQL FIM, IOFS and FQOL. Non-syndromic congenital heart defects were the CA most frequently studied. Through the analysis of comparative studies, we verified that parental and familial QoL were impaired in this population. CONCLUSIONS: This review highlights the relevance of assessing QoL in parents with children with CA and explores the diverse QoL assessment tools described in the literature. Additionally, results indicate a knowledge gap that can help to draw new paths to future research. It is essential to assess QoL as a routine in healthcare providing and to implement strategies that improve it.

Impact in the quality of life of parents of children with chronic diseases using psychoeducational interventions - A systematic review with meta-analysis.

OBJECTIVE: This study aimed to identify psychoeducational interventions applied to parents of children with chronic diseases and evaluate their impact on their quality of life (QoL). METHODS: It was conducted in six databases, complemented by references from the included studies and other reviews, manual search, and contact with experts. We included primary studies on parents of children with chronic diseases that studied psychoeducational interventions versus standard care. RESULTS: We screened 6604 titles and abstracts, reviewed the full text of 60 records, and included 37 primary studies. Half of the studies were on Asthma. We found three intervention formats: one-to-one (43%), groups (49%), and combined approach with individual and group settings (8%). More than 60% of the included studies found statistically significant differences between the intervention and the control group (p < 0.05). CONCLUSION: Several interventions have shown efficacy in improving parental QoL. Despite that, there is insufficient evidence of interventions' implementation. PRACTICE IMPLICATIONS: A holistic approach encompassing the patient and the family's biopsychosocial dimensions is fundamental in successfully managing chronic disease in children. It is vital to design and implement interventions accommodating the common issues experienced by children, parents, and families that deal with chronic childhood conditions. Systematic review registration number PROSPERO 2018 CRD42018092135.

Maternal Diabetes Mellitus as a Risk Factor for High Blood Pressure in Late Childhood.

Intrauterine fetal conditions can have lifelong cardiovascular effects. The impact of maternal diabetes mellitus on children's cardiovascular profile is not well established. The goal of this study was to explore the association between maternal diabetes mellitus and offspring's blood pressure (BP) ≤10 years of age. Generation XXI is a prospective birth cohort, which enrolled 8301 mother-offspring pairs, including 586 (7.1%) children of diabetic mothers. The associations between maternal diabetes mellitus and BP at 4, 7, and 10 years of age was modeled using linear regression. A mixed-effects model was built to assess differences in BP variation over time. Path analysis was used to quantify effects of potential mediators. Maternal diabetes mellitus was associated with higher BP in offspring at the age of 10 (systolic: ß, 1.48; 95% CI, 0.36-2.59; and diastolic: ß, 0.86; 95% CI, 0.05-1.71). This association was independent of maternal perinatal characteristics, and it was mediated by child's body mass index and, to a lesser extent, by gestational age, type of birth, and birth weight (indirect effect proportion, 73%). No significant differences in BP were found at 4 and 7 years of age. Longitudinal analysis showed an accelerated systolic BP increase on maternal diabetes mellitus group (ß, 1.16; 95% CI, 0.03-2.28). These finding were especially relevant in males, suggesting sex differences in the mechanisms of BP prenatal programing. Our results provide further evidence that maternal diabetes mellitus is associated with high BP late in childhood, demonstrating a significant role of child's body mass in the pathway of this association.

Neurocognitive profiles in adolescents and young adults with congenital heart disease.

INTRODUCTION AND OBJECTIVES: The objectives of this study were to assess the neuropsychological performance (NP) of adolescents and young adults with congenital heart disease (CHD), comparing them with a group of healthy controls, to determine whether there are different neurocognitive phenotypes in CHD, and to identify their relation to sociodemographic, neonatal, clinical and psychological adjustment variables. METHODS: A total of 217 CHD patients (116 male, aged 15.73±2.68 years) and 80 controls (35 male, age 16.76±2.22 years) underwent an extensive neuropsychological assessment and analysis of psychological adjustment. RESULTS: CHD patients had significantly poorer NP than healthy controls in all neurocognitive domains. Three different phenotypes of NP in CHD patients were identified: non-impaired (NI), moderately impaired (MI) and globally impaired (GI). They differed in all dimensions of NP. The GI cluster showed fewer years of schooling (p=0.025) and lower neonatal indicators such as head circumference (p=0.019), 1-min Apgar score (p=0.006), birth weight (p=0.05) and length (p=0.034) than the NI cluster. In the MI and GI clusters, there were more cyanotic forms of disease, including tetralogy of Fallot and transposition of the great arteries. The GI cluster presented more difficulties with psychological adjustment, including social (p=0.038), attention (p=0.001) and aggressive (p=0.003) problems. CONCLUSIONS: CHD patients have poorer NP than controls. NP in the CHD group can be classified in three clusters that reflect different levels of neuropsychological functioning, which is sensitive to social, neonatal and psychological adjustment variables.

Fetal Cardiac Function in Maternal Diabetes: A Conventional and Speckle-Tracking Echocardiographic Study.

BACKGROUND: Intrauterine exposure to a diabetic environment is associated with adverse fetal myocardial remodeling. The aim of this study was to assess the biventricular systolic and diastolic function of fetuses exposed to maternal diabetes (MD) compared with control subjects, using a comprehensive cardiac functional assessment and exploring the role of speckle-tracking to assess myocardial deformation. The authors hypothesized that fetuses exposed to MD present signs of biventricular dysfunction, which can be detected by deformation analysis. METHODS: A cross-sectional study was conducted in 129 fetuses with structurally normal hearts, including 76 fetuses of mothers with diabetes and 53 of mothers without diabetes. Maternal baseline characteristics, standard fetoplacental Doppler indices, and conventional echocardiographic and myocardial deformation parameters were prospectively collected at 30 to 33 weeks of gestation. RESULTS: Fetuses of mothers with diabetes had a significantly thicker interventricular septum compared with control subjects (median, 4.25 mm [interquartile range (IQR), 3.87-4.50 mm] vs 3.67 mm [IQR, 3.40-3.93 mm), P < .001), but no effect modification was demonstrated on myocardial deformation analysis. No significant differences were found in conventional systolic and diastolic functional parameters for the left ventricle and right ventricle, except for lower left ventricular cardiac output in the MD group (median, 320 mL/min [IQR, 269-377 mL/min] vs 365 mL/min [IQR, 311-422 mL/min], P < .05]. Deformation analysis demonstrated a significantly lower early diastolic strain rate (SRe) and late diastolic strain rate (SRa) for both ventricles in the MD group (left ventricle: SRe 1.85 ± 0.72 vs 2.26 ± 0.68 sec-1, SRa 1.50 ± 0.52 vs 1.78 ± 0.57 sec-1; right ventricle: SRe 1.57 ± 0.73 vs 1.97 ± 0.73 sec-1, SRa 2 ± 0.77 vs 1.68 ± 0.79 sec-1; P < .05), suggesting biventricular diastolic impairment. Additionally, the right ventricle presented a lower global longitudinal strain in the study group (-13.67 ± 4.18% vs -15.52 ± 3.86%, P < .05). Multivariate analysis revealed that maternal age is an independent predictor of left and right ventricular global longitudinal strain (P < .05), with a significant effect only in MD after group stratification. CONCLUSIONS: Fetuses of mothers with diabetes present signs of biventricular diastolic dysfunction and right ventricular systolic dysfunction by deformation analysis in the third trimester of pregnancy. They may represent a special indication group for functional cardiac assessment, independently of septal hypertrophy. Two-dimensional speckle-tracking could offer an additional benefit over conventional echocardiography to detect subclinical unfavorable changes in myocardial function in this population.

Fetal programming as a predictor of adult health or disease: the need to reevaluate fetal heart function.

Epidemiologic and experimental evidence suggests that adverse stimuli during critical periods in utero permanently alters organ structure and function and may have persistent consequences for the long-term health of the offspring. Fetal hypoxia, maternal malnutrition, or ventricular overloading are among the major adverse conditions that can compromise cardiovascular development in early life. With the heart as a central organ in fetal adaptive mechanisms, a deeper understanding of the fetal cardiovascular physiology and of the echocardiographic tools to assess both normal and stressed pregnancies would give precious information on fetal well-being and hopefully may help in early identification of special risk groups for cardiovascular diseases later in life. Assessment of cardiac function in the fetus represents an additional challenge when comparing to children and adults, requiring advanced training and a critical approach to properly acquire and interpret functional parameters. This review summarizes the basic fetal cardiovascular physiology and the main differences from the mature postnatal circulation, provides an overview of the particularities of echocardiographic evaluation in the fetus, and finally proposes an integrated view of in utero programming of cardiovascular diseases later in life, highlighting priorities for future clinical research.

Longer duration of obesity is associated with a reduction in urinary angiotensinogen in prepubertal children.

BACKGROUND: We aimed to study the impact of obesity on urinary excretion of angiotensinogen (U-AGT) in prepubertal children, focusing on the duration of obesity and gender. Also, we aimed to evaluate whether plasma angiotensinogen (P-AGT) and hydrogen peroxide (H2O2) play a role in the putative association. METHODS: Cross-sectional evaluation of 305 children aged 8-9 years (160 normal weight, 86 overweight, and 59 obese). Anthropometric measurements and 24-h ambulatory blood pressure monitoring were performed. Angiotensinogen (AGT) was determined by a commercial enzyme-linked immunosorbent assay (ELISA) kit and H2O2 by a microplate fluorometric assay. RESULTS: U-AGT and P-AGT levels were similar across body mass index (BMI) groups and between sexes. However, boys who were overweight/obese since the age of 4 years presented lower levels of U-AGT compared with those of normal weight at the same age. In children who were overweight/obese since the age of 4, urinary H2O2 decreased with P-AGT. CONCLUSIONS: A higher duration of obesity was associated with decreased U-AGT in boys, thus reflecting decreased intrarenal activity of the renin-angiotensin system. Also, children with a longer duration of obesity showed an inverse association between urinary H2O2 and P-AGT. Future studies should address whether these results reflect an early compensatory mechanism to limit obesity-triggered renal dysfunction.

Determinants of carotid-femoral pulse wave velocity in prepubertal children.

BACKGROUND: Pulse wave velocity (PWV) is a noninvasive technique to evaluate arterial stiffness, a dynamic property of the vessels, reflecting their structure and function. Childhood obesity is associated with several cardiovascular comorbidities and to the progression of atherosclerosis. We aimed to compare carotid-femoral PWV between normal weight and overweight/obese prepubertal children and to quantify its association with other cardiovascular risk factors. METHODS: Cross-sectional study of 315 children aged 8-9years. Anthropometrics, 24-h ambulatory blood pressure (BP) and carotid-femoral PWV were measured. Classification of obesity was according to World Health Organization (WHO) body mass index (BMI)-for-age reference values. RESULTS: Compared to normal weight children, overweight and obese children presented significantly higher levels of PWV (4.95 (P25-P75: 4.61-5.23), 5.00 (4.71-5.33), 5.10 (4.82-5.50) m/s, respectively; ptrend<0.001). Significant positive correlations were found between PWV and total cholesterol, LDL cholesterol, triglycerides, fasting insulin and insulin resistance levels (HOMA-IR) and with high-sensitivity C-reactive protein (hs-CRP). In a multivariate linear regression model adjusted for sex, age, height and 24-h systolic blood pressure z-score, the independent determinants of PWV were BMI, HOMA-IR and the absence of dipping. CONCLUSIONS: The association between PWV and the loss of dipping and insulin resistance levels, independently of the BMI, reinforces the contribution of these comorbidities to vascular injury in early life.

Left ventricular noncompaction: A rare indication for pediatric heart transplantation.

Isolated left ventricular noncompaction is a rare congenital cardiomyopathy, characterized morphologically by a dilated left ventricle, prominent trabeculations and deep intertrabecular recesses in the ventricular myocardium, with no other structural heart disease. It is thought to be secondary to an arrest of normal myocardial compaction during fetal life. Clinically, the disease presents with heart failure, embolic events, arrhythmias or sudden death. Current diagnostic criteria are based on clinical and imaging data and two-dimensional and color Doppler echocardiography is the first-line exam. There is no specific therapy and treatment is aimed at associated comorbidities. Cases refractory to medical therapy may require heart transplantation. The authors describe a case of severe and refractory heart failure, which was the initial presentation of isolated left ventricular noncompaction in a previously healthy male child, who underwent successful heart transplantation.

Gender and obesity modify the impact of salt intake on blood pressure in children.

BACKGROUND: Most modifiable risk factors for high blood pressure (BP), such as obesity and salt intake, are imprinted in childhood and persist into adulthood. The aim of our study was to evaluate the intake of salt in children and to assess its impact on BP taking into account gender and nutritional status. METHODS: A total of 298 children aged 8-9 years were evaluated in a cross-sectional study. Anthropometric measurements and 24-h ambulatory monitoring were performed, and salt intake was determined by 24-h urinary sodium excretion. RESULTS: The average estimated salt intake among the entire cohort of children enrolled in the study was 6.5 ± 2.2 g/day, and it was significantly higher in boys than in girls (6.8 ± 2.4 vs. 6.1 ± 1.9 g/day, respectively; p = 0.018) and in overweight/obese children than in normal weight children (6.8 ± 2.4 vs. 6.1 ± 2.0 g/day, respectively; p = 0.006). Salt intake exceeded the upper limit of the US Dietary Reference Intake in 72% of children. Daytime systolic BP increased by 1.00 mmHg (95% confidence interval 0.40-1.59) per gram of daily salt intake in overweight/obese boys, but not in normal weight boys or in girls. CONCLUSIONS: Our results demonstrate an extremely high salt intake among 8- to 9-year-old Portuguese children. Higher salt intake was associated with higher systolic BP in boys, specifically in those who were overweight/obese. Longitudinal studies are needed to further evaluate the causal relationship between obesity and high BP and the mechanism by which salt intake modulates this relationship. Nonetheless, based on our results, we urge that dietary salt reduction interventions, along with measures to fight the global epidemic of obesity, be implemented as early in life as possible.

Association of myeloperoxidase levels with cardiometabolic factors and renal function in prepubertal children.

INTRODUCTION: Myeloperoxidase (MPO), an enzyme linking obesity and cardiovascular (CV) risk in adults, has rarely been studied in young children and no studies assessed its association with renal function. We sought to explore a possible association between serum MPO levels, obesity, CV risk factors and renal function in prepubertal children. MATERIALS/METHODS: Cross-sectional evaluation of 309 children aged 8-9 years (161 normal weight, 148 overweight/obese), members of the birth cohort Generation I (Portugal). Anthropometrics (body mass index (BMI), waist-to-height ratio (WHtR) and % body fat mass (%BFM) by bioelectrical impedance analysis), 24-h ambulatory blood pressure monitoring and pulse wave velocity (PWV) were measured. Insulin resistance was estimated by the HOMA index (considering serum fasting glucose and insulin determinations). Serum MPO levels were assessed by immunoenzymatic assay. RESULTS: MPO levels were positively associated with obesity indices (BMI z-score, WHtR and %BFM). Higher MPO levels were associated with higher 24-h and night-time mean arterial pressure, with nondipping and with higher values of insulin resistance. In normal weight children, the endothelial function, as evaluated indirectly by PWV, was an independent predictor of MPO levels. In overweight/obese children, estimated glomerular filtration rate increased significantly across tertiles of MPO (Ptrend = 0·031) and this association held after adjustment for age, sex, neutrophil and monocyte counts and CV risk factors. CONCLUSIONS: Our results reinforce the role of MPO as a risk marker in obesity and related CV morbidities in young children. MPO levels associate with the dipping pattern and PWV and, among overweight/obese children, an association exists between MPO and renal function.