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Evaluation of cardiac remodeling in pediatric chronic kidney disease by cardiovascular magnetic resonance

BMC Cardiovascular Disorders volume 24, Article number: 526 (2024) Cite this article

Abstract

Background

Children with chronic kidney disease (CKD) are at high risk of cardiovascular disease. Cardiovascular magnetic resonance (CMR) is the reference method for assessing cardiac remodeling. To our knowledge, no study has reported a comprehensive analysis of left ventricular(LV) cardiac remodeling using CMR in different stages of pediatric CKD. This prospective case-control study aimed to investigate cardiac remodeling in pediatric CKD, using CMR, and determine its relationship with risk factors.

Method

CMR was performed in 124 children with CKD and 50 controls. The cardiac remodeling parameters included left ventricular mass index (LVMI), LV remodeling index (LVRI), and LV wall thickness. Univariable and multivariable analyses were performed to assess the cardiac remodeling risk factors.

Results

Cardiac remodeling was observed in 35.5% (44/124) of children with CKD. The LVMI, LVRI, and LV wall thickness were higher in advanced stages of CKD (P < 0.05). In the CKD stage 1–2 group, a lower in the estimated glomerular filtration rate was an independent determinant of impaired LVMI (β = −0.425, P = 0.019) and LVRI (β = −0.319, P = 0.044). A higher protein to creatinine ratio(PCR) was independently associated with impaired LVRI (β = 0.429, P = 0.022). In the CKD stage 3–5 group, higher in systolic blood pressure (SBP) (β = 0.464, P = 0.005) and PCR (β = 0.852, P = 0.031) were independent determinants of impaired LVMI. Additionally, higher SBP was positively correlated with impaired LVRI(r = 0.599, P < 0.001). There was a trend toward more abnormal cardiac remodeling in the CKD stage 3–5 group with hypertension than those without.

Conclusion

Cardiac remodeling is prevalent in children with CKD, from an early stage. kidney markers are independently associated with cardiac remodeling. Hypertension increases the risk of cardiac remodeling in CKD stages 3–5. Strict BP control may help reverse or prevent remodeling.

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Background

Chronic kidney disease (CKD) is a state of irreversible kidney damage and/or progressive loss of kidney function over time [1]. Nearly 700 million people worldwide have CKD. It is increasingly recognized as a global public health problem that places an enormous medical and financial burden on societies and healthcare systems [2,3,4]. The estimated incidence of CKD in the pediatric population is 15–74.7 per million [5], but this is likely to be an underestimate because the early stages of CKD are usually asymptomatic. Patients with CKD are at a high risk of cardiovascular disease (CVD). Approximately 50% of patients with CKD stages 4–5 have CVD [6,7,8] and cardiovascular mortality accounts for 33–36% of all deaths in children on dialysis [9,10,11]. The major phenotype of fatal CVD in patients with CKD is uremic cardiomyopathy with diastolic dysfunction, left ventricular(LV) remodeling and hypertrophy, and fibrosis [12]. Among these, cardiac remodeling is defined as a change in the structure of the heart in response to hemodynamic load and/or cardiac injury. It can develop early in the course of CKD. The prevalence of left ventricular hypertrophy (LVH) detected by echocardiography has been reported to be 20–30% in children with stages 2–4 CKD, increasing to 85% in patients on maintenance dialysis [12, 13]. While LVH is initially a compensatory adaptive response, continued LV overload leads to cardiomyocyte death which will eventually lead to systolic heart failure, arrhythmias, and sudden death [14,15,16]. A study of patients with uremia treated with hemodialysis reported that 47% had LVH, 46% had ventricular premature beats, and 27% had high-grade arrhythmias [17, 18]. Factors such as chronic hypertension, obesity, malnutrition, dyslipidemia, proteinuria and metabolic bone disease may contribute to increased cardiac remodeling and hypertrophy [19]. The pathogenesis of LVH in children with CKD is multifactorial and incompletely understood. Therefore, identifying and treating modifiable risk factors for LV remodeling and hypertrophy in children with CKD is important to reduce or eliminate the risk for short and long-term CVD morbidity and mortality [20].

Most previous studies have used transthoracic echocardiography to assess cardiac remodeling [21, 22]. However, this suffers from limited acoustic windows and operator dependence [23]. Cardiovascular magnetic resonance (CMR) imaging overcomes these limitations and is the reference method for assessing cardiac geometry and remodeling. To our knowledge, no study has reported a comprehensive analysis of LV cardiac remodeling using CMR in different stages of pediatric CKD. The objectives of this study were to (i) use CMR to explore whether children with CKD have cardiac remodeling and whether the type differs at different stages of CKD, (ii) determine whether there is a relationship between cardiac remodeling and risk factors.

Materials and methods

Study population

Children with CKD were recruited for this prospective case-control study between April 2019 and November 2022. CKD is defined as structural or functional kidney damage that persists for at least 3 months, based on the clinical practice guidelines from Kidney Disease: Improving Global Outcomes (KDIGO) [1]. Functional damage is characterized by a sustained reduction in the estimated glomerular filtration rate (eGFR), persistent elevation of urinary protein excretion, or both. CKD is classified into 5 stages according to the KDIGO guidelines based on eGFR [1]. In our study, the CKD patients were divided into 2 groups based on the severity of CKD [24]: CKD stage 1–2 (early CKD), CKD stage 3–5 (moderate to severe CKD). The exclusion criteria were congenital structural heart disease or primary myocardial disease, severe arrhythmia, hyperthyroidism, tumor, claustrophobia, inability to cooperate during CMR, and poor image quality. Also included in this study were healthy children of age and sex matching the case group who underwent routine physical examination at our hospital or were recruited through posters as a control group with the same exclusion criteria as the case group.The study protocol was approved by the institutional review board (IRB) of our hospital(IRB reference number - K2019061,30/04/2020, clinical trial registration number - ChiCTR2100053084,10/11/2021). Patient participation was voluntary, and all subjects themselves and their guardians were enrolled in the study after agreeing to participate and signing an informed consent form. All patient sensitive information was kept strictly confidential and used only for the purposes of this study.

Clinical assessment and laboratory analysis

At the time of the CMR scan, the height and weight of all participants were measured twice, and the average values used to calculate their body mass index (BMI) and body surface area (BSA). Resting blood pressure (BP) was recorded as the average of three measurements in the arm taken 5 min apart while seated for at least 10 min. The hypertension diagnostic criteria were obtained from the “Updating blood pressure references for Chinese children aged 3–17 years” issued by the Chinese child BP references collaborative group in 2017 [25]. The patients’ clinical information included the CKD etiology, drug use records, and complications. A week before and after CMR, all CKD participants had blood and urine tests including hemoglobin, urea, creatinine, cystatin C, and protein to creatinine ratio (PCR) measurements. The eGFR was estimated by the modified Schwartz formula.

Imaging protocol

CMR images were obtained using a clinical whole-body 3T CMR scanner (MAGNETOM Skyra, Siemens Healthineers, Erlangen, Germany) with a dedicated 18-channel receiver coil. All images were acquired during breath-holding in end-expiration, and standard electrocardiographic gating was used. A balanced steady-state free-precession pulse sequence with breath-hold was performed to obtain cine images. These comprised 8–12 continuous sections from the mitral valve level to the LV apex in the short-axis view and one two-, three-, and four-chamber long-axis slices. The acquisition parameters were: repetition time [TR] = 3.4 ± 2 ms, echo time [TE] = 1.48 ms, flip angle = 34°, slice thickness = 8.0 mm, matrix = 126 × 224 pixels, and field of view [FOV] = 300 × 241 mm2 [26]. No gadolinium–contrast was given.

CMR image analysis and calculations

CMR analysis was performed by two experienced radiologists, blinded to the patients’ baseline characteristics, using commercially available CVI 42 software (V.5.9.3; Circle Cardiovascular Imaging Inc., Calgary, Alberta, Canada). The software’s artificial intelligence function automatically identifies the endocardial and epicardial contours of the LV at end-diastole and end-systole. Images that were not accurately identified by the artificial intelligence were manually adjusted to ensure that the selected temporal phases and contours matched exactly. The endocardial and epicardial contours were drawn excluding the myocardial trabeculae and papillary muscles according to current guidelines [27]. LV function parameters, including LV ejection fraction (LVEF), LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV stroke volume (LVSV), LV cardiac output (LVCO), and LV mass were calculated automatically. LVEDV, LVESV, LVSV, LVCO, and LV mass were indexed to BSA (LVEDVI, LVESVI, LVSVI, LVCI and LVMI) [28]. The LV remodeling index (LVRI) was calculated with the formula LVRI = LV mass/LVEDV [29, 30]. LV wall thickness was determined by the average of the end-diastolic wall of each segment of the LV [31]. The type of cardiac remodeling was determined based on the 95th percentile values of LVRI and LVMI in a healthy cohort [32]. Four categories were defined [32] (Fig. 1): Normal remodeling was defined as LVMI and LVR values below the 95th percentile of the healthy cohort. Concentric remodeling was identified by LVRI above the 95th percentile only. Eccentric hypertrophy was characterized by LVMI values above the 95th percentile only. Concentric hypertrophy was classified as both LVMI and LVRI values above the 95th percentile.

Fig. 1
figure 1

Diagram of cardiac remodeling [32]. The type of cardiac remodeling was determined based on the 95th percentile values of LVRI and LVMI in the healthy cohort. Normal = below the 95th percentile for both LVMI and LVR; Concentric remodeling = above the 95th percentile for LVRI ratio only; Eccentric hypertrophy = above the 95th percentile for LVMI only; Concentric hypertrophy = above the 95th percentile for both LVMI and LVRI. Abbreviations: LVMI = left ventricle mass index; LVRI = left ventricular remodeling index

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Statistics

Statistical analyses were performed using SPSS 26.0 (IBM SPSS Inc., Armonk, New York, USA) and Prism 9.0 (GraphPad software Inc., San Diego, California, USA). Continuous variables are presented as the mean value with standard deviation or median with interquartile range (IQR). Categorical variables are presented as absolute frequencies and percentages. Normality was evaluated using the Shapiro-Wilk test, and homogeneity of variance with Levene’s test. The demographics and CMR results of the CKD groups and healthy controls were compared using the Kruskal-Wallis test or one-way ANOVA. The Mann-Whitney U test or independent Student’s t-test was used to assess the difference in demographics and CMR results between CKD stage 1–2 and CKD stage 3–5. The frequencies of qualitative data or categorical variables such as etiology, medication use, CKD complications, and the different remodeling types of the CKD stage 1–2 group and CKD stage 3–5 group, were compared using the chi-squared test, the chi-squared test correction formula, or Fisher’s exact probability method. Pearson’s or Spearman’s correlation coefficients were used for continuous parametric and nonparametric variables, respectively. Linear regression analyses were performed to assess the effect of potential risk factors on LVRI and LVMI in patients with CKD. Factors of clinical interest and those significant on univariate analysis (P < 0.05) were considered for inclusion in the multiple linear regression model. Interobserver and intraobserver variability for continuous CMR variables were evaluated using interclass correlation coefficients (ICC). All tests were 2-sided, and a P value < 0.05 was considered statistically significant.

Results

Baseline characteristics of the study population

In all, 129 children with CKD were enrolled in the study. Of these, 2 had congenital heart disease, and 3 had poor image quality and were excluded from data analysis. A total of 52 cases were included in the healthy control group, of which 2 cases with poor image quality were excluded. As a result, a total of 124 CKD patients (11.7 ± 3.0 years; 51% male) and 50 healthy controls (11.5 ± 3.1 years; 50% male) were finally included. The CKD cohort consisted of 90 children in the CKD stage 1–2 group (eGFR:153.8 ± 4.6 ml/min/1.73 m2) and 34 children in the CKD stage 3–5 group (eGFR:16.3 [12.4–49.8] ml/min/1.73 m2). Table 1 summarizes the demographics and clinical assessment of the study population. There was no difference in age (P = 0.771), sex (P = 0.782), or weight (P = 0.058) between participants with CKD and healthy controls. However, there were differences in weight, BMI, BSA, heart rate (HR), systolic blood pressure (SBP), and diastolic BP (DBP) between them (all P < 0.05). Specifically, there was a tendency for the CKD stage 1–2 group to have a higher body weight (44.5 ± 14.2 kg vs. 38.7 ± 11.4 kg, P = 0.014), BMI (20.8 ± 4.6 kg/m2 vs. 17.7 ± 2.3 kg/m2, P < 0.001) and BSA (1.32 ± 0.25 m2 vs. 1.25 ± 0.26 m2, P = 0.095) compared to normal controls. As the disease progressed, the CKD stage 3–5 group tended to have lower body weight (30.0 [21.5–40.6] kg vs. 38.7 ± 11.4 kg, P = 0.018), BMI (17.2 [15.7–19.4] kg/m2 vs. 17.7 ± 2.3 kg/m2, P = 0.012) and BSA (1.11 ± 0.33 m2 vs. 1.25 ± 0.26 m2, P = 0.049) compared with normal controls. The HR, SBP and DBP increased with CKD progression (all P < 0.05). There were more hypertensive patients in the CKD stage 3–5 group (16/34,47.1%) than in the CKD stage 1–2 group (2/90,2.2%) (P < 0.001). The etiology of CKD varied (P < 0.001), with primary nephrotic syndrome (37/90,41.1%), lupus nephritis (24/90, 26.7%), and Henoch-Schonlein purpura nephritis (20/90, 22.2%) predominating in the CKD stage 1–2 group and hereditary glomerular diseases (13/34, 38.2%) in the CKD stage 3–5 group. As expected, markers of kidney function (urea, creatinine, and eGFR) were worse in the CKD stage 3–5 group (all P < 0.05), and there were also more complications (all P < 0.05).

Table 1 Demographics and baseline characteristics of study population
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Cardiac remodeling

LVMI (39.51 [35.65–46.22] g/m2 vs. 37.37 [34.54–42.19] g/m2, P = 0.016), LVRI (0.61 g/ml ± 0.12 vs. 0.52 ± 0.05 g/ml, P < 0.001) and LV wall thickness (5.24 ± 0.81 mm vs. 4.67 ± 0.63 mm, P = 0.001) were significantly greater in children with CKD compared to healthy controls. However, there were no differences in LVEF, LVEDV, LVESVI, LVSVI, or LVCI (all P > 0.05) between the two groups (Table 2). Subgroup analysis of cardiac geometry and function revealed that LVMI, LVRI, and LV wall thickness were more prevalent in higher stages of CKD (all P < 0.05) (Fig. 2). The 95th percentile cut-off for LVMI derived in the healthy weight cohort was 52.5 g/m2 and the 95th percentile cut-off for LVRI was 0.63. Further analysis showed that 35.5% (44/124) of children with CKD had cardiac remodeling. Further, the proportion of cardiac remodeling in the CKD stage 3–5 group (64.7%, 22/34) was much higher than in the CKD stage 1–2 group (24.4%, 22/90) (P < 0.001). A schematic diagram of the cardiac remodeling patterns in the different subgroups of CKD is shown in Fig. 3. In the CKD stage 1–2 group, 19 (21.1%) children had concentric remodeling and 3 (3.3%) had concentric hypertrophy, whereas the remaining 75.6% (68/90) had normal geometry. In contrast, 64.7% (22/34) children in the CKD stage 3–5 group had cardiac remodeling, with concentric remodeling, concentric hypertrophy, and eccentric hypertrophy in 20.6% (7/34), 26.5% (9/34) and 17.6% (6/34), respectively. The remaining 35.3% (12/34) of the children had normal geometry.

Table 2 Cardiac geometry, function and remodeling
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Fig. 2
figure 2

Cardiac remodeling markers in different groups. LVMI (A), LVRI (B) and LV wall thickness (C) tended to increase with worsening CKD. Abbreviations: CKD = chronic kidney disease; LV = left ventricle; LVMI = left ventricle mass index; LVRI = left ventricular remodeling index. * p < 0.05

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Fig. 3
figure 3

Distribution of cardiac remodeling types by different groups.Normal geometry and concentric remodeling predominated in the CKD1–2 group, while the proportion of concentric or eccentric hypertrophy increases in the CKD3–5 group compared with the CKD1–2 group. Abbreviations: CKD = chronic kidney disease; LVMI = left ventricle mass index; LVRI = left ventricular remodeling index

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Relationship between cardiac remodeling and risk factors

In children with CKD, cardiac remodeling markers LVMI and LVRI significantly correlated with eGFR, PCR, and SBP (all P < 0.05). In the CKD stage 1–2 group, the univariable analysis showed that eGFR and PCR were associated with impaired LVMI and LVRI (all P < 0.05) (Table 3). SBP was associated with impaired LVMI (r = 0.308, P = 0.003), but not with LVRI (r = 0.187, P = 0.077). After multivariable adjustment, eGFR remained an independent determinant of impaired LVMI (β = −0.425, P = 0.019), and LVRI (β = −0.319, P = 0.044) in children with CKD stages 1–2. However, PCR was independently associated only with impaired LVRI (β = 0.429, P = 0.022). Univariable analysis in the CKD stage 3–5 group showed that SBP, eGFR, PCR, and cystatin C were associated with impaired LVMI (all P < 0.05) (Table 4). After multivariable adjustment, SBP (β = 0.464, P = 0.005) and PCR (β = 0.852, P = 0.031) remained the independent determinants of impaired LVMI. Impaired LVRI was only independently associated with SBP (r = 0.599, P < 0.001).

Table 3 Influence of clinical and kidney biomarkers for prediction of cardiac remodeling in CKD stage 1–2 group
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Table 4 Influence of clinical and kidney biomarkers for prediction of cardiac remodeling in CKD stage 3–5 group
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Subgroup analysis of SBP in the CKD stage 3–5 group

There were 18 children with hypertension among the children with CKD, 16 of whom had CKD stages 3–5. Therefore, only the CKD stage 3–5 group was analyzed as a subgroup. Compared with the non-hypertensive subgroup, the hypertensive subgroup exhibited significantly higher LVMI and LV wall thickness (LVMI: 61.4 ± 3.8 g/m2 vs. 48.7 ± 3.1 g/m2, P = 0.002; LV wall thickness: 6.27 ± 0.23 cm vs. 5.24 ± 0.29 mm, P = 0.004). There was a trend toward higher LVRI in the hypertensive subgroup, although there was no statistical difference (0.71 ± 0.04 g/ml vs. 0.64 ± 0.03 g/ml, P = 0.154).

In the CKD stage 3–5 group, there was a trend toward more abnormal cardiac remodeling in children with hypertension than in children without hypertension (P = 0.039; Fig. 4). In the hypertension subgroup, almost half of the children (43.8%, 7/16) had concentric hypertrophy and a quarter (25.0%, 4/16) of the children had eccentric hypertrophy. In contrast, in the non-hypertension subgroup, 50.0% (9/18) of the children showed normal geometry, 27.8% of the children had concentric remodeling and 22.2% had concentric or eccentric hypertrophy.

Fig. 4
figure 4

Percentage stacking chart of cardiac remodeling types in CKD stage 3–5 with and without hypertension. There was a trend towards a more abnormal cardiac remodeling in children with hypertension, with approximately 68.8% of children having concentric or eccentric hypertrophy in the hypertension subgroup.Abbreviations: CKD = chronic kidney disease

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Reproducibility analysis

The LV mass, LVEDV, and LVESV of 37 children with CKD were randomly selected and analyzed for intraobserver and interobserver reliability. The reproducibility (Intraobserver ICC = 0.899–0.945, Interobserver ICC = 0.907–0.972) of the cardiac geometry measurements were considered excellent.

Discussion

This was a prospective case-control study to investigate changes in cardiac remodeling in pediatric CKD using CMR. We found that cardiac remodeling is prevalent, even in the early stages of CKD(stage 1–2). Cardiac remodeling markers represented by LVMI, LVRI and LV wall thickness tended to increase with the increasing stage of CKD. The proportion of concentric or eccentric hypertrophy increased in the CKD stage 3–5 group compared with the CKD stage 1–2 group. The kidney biomarkers eGFR and PCR were independent determinants of impaired LVMI or LVRI. Furthermore, In the CKD stage 3–5 group, SBP was also independently associated with impaired LVMI and LVRI.

Cardiac remodeling occurs to maintain cardiac function and reduce left ventricular wall stress during conditions of increased afterload and preload [13]. In our study using CMR, we found that 35.5% of children with CKD had cardiac remodeling. Notably, 24.4% of children with CKD stages 1–2 had cardiac remodeling, while the proportion of cardiac remodeling in the CKD stage 3–5 group was greater, at 64.7%. This is in line with a European study in which LVH was identified in 14.9% of children with CKD stage 3a and in 48% with CKD stage 5 [21]. LVH prevalence has also been reported as 20–30% in children with CKD stages 2–4, compared to 85% in patients on chronic hemodialysis [12, 13]. These findings suggest that cardiac remodeling may occur in the early stages of CKD and increase in prevalence as CKD progresses. In addition, we found that normal geometry and concentric remodeling predominated in the CKD stage 1–2 group, whereas concentric or eccentric hypertrophy was more prevalent in the CKD stage 3–5 group, reaching 26.5% and 17.6%, respectively. Cardiac remodeling and hypertrophy occur in two distinct geometric patterns: pressure overload leads to concentric cardiac remodeling, while volume overload or isotonic exercise leads to eccentric hypertrophy [33].

The risk factors influencing cardiac remodeling are complex and can be divided into two primary groups: traditional risk factors and CKD-related risk factors [13, 19]. Our study found that the kidney biomarkers eGFR and PCR were independent determinants of impaired LVMI or LVRI. Another study of 120 children in London found that worsening eGFR was associated with higher LVRI [34]. Other risk factors associated with CKD have also been reported, including the retention of uremic toxins, anemia, inflammation, abnormal bone mineral metabolism, and growth factors [20, 35, 36].

Traditional cardiovascular risk factors, such as hypertension are prevalent in CKD patients. In our study, 47% of children in the CKD stage 3–5 group had hypertension. There was a trend toward more abnormal cardiac remodeling in children with and without hypertension, and SBP was associated with impaired LVMI and LVRI. In the 4 C study, hypertension was present in 24.4–47.4% of children with CKD stage 3a and CKD stage 5 [21]. The Chronic Kidney Disease in Children (CKiD) study in the USA also found that 37% of children had hypertension, and every 10% increase in systolic BP load increased the odds of LVH 1.1-fold [37]. Strict BP control is effective in slowing the progression of CKD and reducing the frequency of LVH in children [38, 39]. However, the optimal target BP in patients with CKD has not yet been established [40].

Other traditional factors associated with CKD in children include obesity and dyslipidemia. The CKiD study revealed that adiposity was independently associated with LVH. The odds of LVH were 1.5-fold higher in boys and 3.1-fold higher in girls per unit increase of BMI z-score [22]. Our observations suggest a trend toward increased weight in the CKD stage 1–2 group, possibly due to increased glucocorticoid use for secondary glomerular disease leading to obesity. There was a trend toward decreased weight in the CKD stage 3–5 group, likely due to hereditary glomerular diseases causing growth failure. Despite this, our multivariate analysis did not identify a significant relationship between BMI and LV remodeling, which may be due to differing causes of morbidity in our study compared to others.

Cardiac remodeling and hypertrophy are compensatory adaptive responses. However, persistent LV overload can lead to cardiomyocyte death, suggesting that remodeling may have a pathological significance [14]. It remains unclear whether correcting these risk factors can improve cardiac remodeling due to their complex interplay. Successful kidney transplantation has been shown to decrease LVMI and the prevalence of LVH in children with end-stage kidney disease [41]. In heart failure patients, the use of angiotensin-converting enzyme inhibitors and some beta-blockers, which are associated with improved survival, can slow or, in some cases, reverse cardiac remodeling parameters [42,43,44]. In our cross-sectional study, we only evaluated risk factors that influence cardiac remodeling in children with CKD. A prospective longitudinal cohort study is needed to determine whether controlling these factors can reduce remodeling and subsequent cardiac morbidity and mortality in these patients.

In addition to the cardiac remodelling markers investigated in our study using CMR, there are other biomarkers associated with CKD, including NT-proBNP and hs-cTnT, which have been strongly associated with cardiac remodelling abnormalities and increased cardiovascular mortality risk in CKD patients [45, 46]. These biomarkers offer potential insights into the underlying mechanisms and prognostic significance of cardiac dysfunction in paediatric CKD. Therefore, we advocate their inclusion in future studies to improve our understanding of cardiac health in this vulnerable population.Furthermore, it is imperative to acknowledge that paediatric CKD patients may experience a wide range of cardiac changes that go beyond mere remodelling. In particular, myocardial fibrosis, edema and aortic stiffness are emerging as critical factors that significantly influence cardiac function and prognosis [47]. To achieve a deeper and more nuanced understanding of their cardiac health status, future cohort studies should broaden their scope beyond traditional CMR markers of remodelling and incorporate advanced CMR technologies that can provide deeper insights into myocardial tissue properties, edema and vascular function.

Limitations

The main limitation of this study is its cross-sectional design. Although it provides important insights into the relationship between cardiac remodeling, kidney biomarkers, and BP in children with CKD, longitudinal follow-up would help further understanding of the complex interplay between risk factors and cardiovascular health. Another limitation is that this was a single-center study with a relatively small number of patients. Therefore, to optimize the statistical power for group differences, we stratified the patients into only 2 groups: early CKD, moderate to severe CKD. This stratification method can be considered scientifically sound because it is consistent with the recognized pathophysiological progression of CKD, with cardiac involvement tending to be less pronounced in the early stages and more pronounced in the moderate to severe stages. Furthermore, this categorization approach is supported by relevant literature sources.

Conclusions

Cardiac remodeling is prevalent in children with CKD, even in the early stages. CKD stages 1–2 mostly have normal geometry or concentric remodeling, while CKD stages 3–5 have more concentric or eccentric hypertrophy. kidney markers are independently associated with cardiac remodeling. Hypertension increases the risk of cardiac remodeling in CKD stages 3–5, suggesting that controlling BP may help reverse or prevent adverse changes.

Data availability

All datasets during this study are available from the corresponding author on reasonable request.

Abbreviations

BP:

Blood pressure

BSA:

Body surface area

CKD:

Chronic kidney disease

CMR:

Cardiovascular magnetic resonance

CVD:

Cardiovascular disease

DBP:

Diastolic blood pressure

eGFR:

estimated glomerular filtration rate

HR:

Heart rate

ICC:

Interclass correlation coefficients

IRB:

Institutional review board

KDIGO:

Kidney Disease: Improving Global Outcomes

LV:

Left ventricular

LVCO:

Left ventricular cardiac output

LVEDV:

Left ventricular end-diastolic volume

LVEF:

Left ventricular ejection fraction

LVESV:

Left ventricular end-systolic volume

LVH:

Left ventricular hypertrophy

LVMI:

Left ventricular mass index

LVRI:

Left ventricular remodeling index

LVSV:

Left ventricular stroke volume

PCR:

Protein to creatinine ratio

SBP:

Systolic blood pressure

SD:

Standard deviation

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Acknowledgements

Not applicable.

Funding

This work was supported by National Natural Science Foundation of China (82120108015, 82102020, 82071874, 81971586) and Sichuan Science and Technology Program (2020YJ0029, 21ZDYF1967).

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Author notes

  1. Sisi Song and Linjun Xie contributed equally to this work.

Authors and Affiliations

  1. Department of Radiology, West China Second University Hospital, Sichuan University, Chengdu, China

    Sisi Song, Linjun Xie, Huayan Xu, Ke Xu, Hang Fu, Lu Zhang, Ruilai Hou & Yingkun Guo

  2. Key Laboratory of Birth Defects and Related Diseases of Women and Children, (Sichuan University), Ministry of Education, Chengdu, China

    Sisi Song, Linjun Xie, Huayan Xu, Ke Xu, Hang Fu, Lu Zhang, Ruilai Hou, Yuhong Tao & Yingkun Guo

  3. Department of Radiology, Deyang People’s Hospital, Deyang, Sichuan, China

    Sisi Song

  4. Department of Radiology, West China Hospital of Stomatology, Sichuan University, Chengdu, China

    Ruilai Hou

  5. Division of Nephrology, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China

    Yuhong Tao

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Contributions

Sisi Song, Linjun Xie, Huayan Xu, Yuhong Tao and Yingkun Guo designed this study. Sisi Song, Linjun Xie, Lu Zhang and Ruilai Hou collected data.Sisi Song, Ke Xu and Hang Fu analyzed the data.Sisi Song and Linjun Xie wrote the manuscript text. All authors contributed to the article and approved the submitted version.

Corresponding authors

Correspondence to Yuhong Tao or Yingkun Guo.

Ethics declarations

Ethics approval and consent to participate

The study protocol complied with the requirements of the Declaration of Helsinki, was reviewed by the Institutional Review Board of West China Second University Hospital of Sichuan University (Ethics No.: K2019061,30/04/2020), and the clinical trial registration was completed and approved by the China Clinical Trial Registry (Registration No.: ChiCTR2100053084,10/11/2021). Before the cardiac magnetic resonance examination, the investigators explained the purpose of the study, the enrollment procedure, the risks of the CMR examination, the contingency plan for unforeseen events, and the benefits of the study to all children with CKD, children in the normal control group, and their families. The subjects themselves and their guardians were enrolled in the study after agreeing to participate and signing an informed consent form. All patient sensitive information was kept strictly confidential and used only for the purposes of this study.

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The authors declare no competing interests.

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Song, S., Xie, L., Xu, H. et al. Evaluation of cardiac remodeling in pediatric chronic kidney disease by cardiovascular magnetic resonance. BMC Cardiovasc Disord 24, 526 (2024). https://doi.org/10.1186/s12872-024-04179-1

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BMC Cardiovascular Disorders

ISSN: 1471-2261

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