Dataset Information

Intimal and medial arterial changes defined by ultra-high-frequency ultrasound: Response to changing risk factors in children with chronic kidney disease.

ABSTRACT:

Background

Patients with chronic kidney disease (CKD) are exposed to both traditional 'Framingham' and uremia related cardiovascular risk factors that drive atherosclerotic and arteriosclerotic disease, but these cannot be differentiated using conventional ultrasound. We used ultra-high-frequency ultrasound (UHFUS) to differentiate medial thickness (MT) from intimal thickness (IT) in CKD patients, identify their determinants and monitor their progression.

Methods

Fifty-four children and adolescents with CKD and 12 healthy controls underwent UHFUS measurements using 55-70MHz transducers in common carotid and dorsal pedal arteries. Annual follow-up imaging was performed in 31 patients.

Results

CKD patients had higher carotid MT and dorsal pedal IT and MT compared to controls. The carotid MT in CKD correlated with serum phosphate (p<0.001, r = 0.42), PTH (p = 0.03, r = 0.36) and mean arterial pressure (p = 0.03, r = 0.34). Following multivariable analysis, being on dialysis, serum phosphate levels and mean arterial pressure remained the only independent predictors of carotid MT (R2 64%). Transplanted children had lower carotid and dorsal pedal MT compared to CKD and dialysis patients (p = 0.02 and p = 0.01 respectively). At 1-year follow-up, transplanted children had a decrease in carotid MT (p = 0.01), but an increase in dorsal pedal IT (p = 0.04) that independently correlated with annualized change in BMI.

Conclusions

Using UHFUS, we have shown that CKD is associated with exclusively medial arterial changes that attenuate when the uremic milieu is ameliorated after transplantation. In contrast, after transplantation intimal disease develops as hypertension and obesity become prevalent, representing rapid vascular remodeling in response to a changing cardiovascular risk factor profile.

SUBMITTER: Dangardt F

PROVIDER: S-EPMC6002120 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Intimal and medial arterial changes defined by ultra-high-frequency ultrasound: Response to changing risk factors in children with chronic kidney disease.

Dangardt Frida F Charakida Marietta M Chiesa Scott S Bhowruth Devina D Rapala Alicja A Thurn Daniela D Schaefer Franz F Deanfield John J Shroff Rukshana R

PloS one 20180614 6

<h4>Background</h4>Patients with chronic kidney disease (CKD) are exposed to both traditional 'Framingham' and uremia related cardiovascular risk factors that drive atherosclerotic and arteriosclerotic disease, but these cannot be differentiated using conventional ultrasound. We used ultra-high-frequency ultrasound (UHFUS) to differentiate medial thickness (MT) from intimal thickness (IT) in CKD patients, identify their determinants and monitor their progression.<h4>Methods</h4>Fifty-four childr ...[more]

PMID: 29902198

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Project description:BackgroundArterial medial calcification (AMC) is a common complication in individuals with chronic kidney disease (CKD), which can lead to cardiovascular morbidity and mortality. The progression of AMC is controlled by a key transcription factor called runt-related transcription factor 2 (RUNX2), which induces vascular smooth muscle cells (VSMCs) transdifferentiation into an osteogenic phenotype. However, RUNX2 has not been targeted for therapy due to its essential role in bone development. The objective of our study was to discover a RUNX2 coactivator that is highly expressed in arterial VSMCs as a potential therapy for AMC.MethodsWe employed transcriptomic analysis of human data and an animal reporter system to pinpoint four and a half LIM domains 2 (FHL2) as a potential target. Subsequently, we investigated the mRNA and protein expression patterns of FHL2 in the aortas of both human and animal subjects with CKD. To examine the role of FHL2 in the RUNX2 transcription machinery, we conducted coimmunoprecipitation and chromatin immunoprecipitation experiments. Next, we manipulated FHL2 expression in cultured VSMCs to examine its impact on high phosphate-induced transdifferentiation. Finally, we employed FHL2-null mice to confirm the role of FHL2 in the development of AMC in vivo.ResultsAmong all the potential RUNX2 cofactors, FHL2 displays selective expression within the cardiovascular system. In the context of CKD subjects, FHL2 undergoes upregulation and translocation from the cytosol to the nucleus of arterial VSMCs. Once in the nucleus, FHL2 interacts structurally and functionally with RUNX2, acting as a coactivator of RUNX2. Notably, the inhibition of FHL2 expression averts transdifferentiation of VSMCs into an osteogenic phenotype and mitigates aortic calcification in uremic animals, without causing any detrimental effects on the skeletal system.ConclusionThese observations provide evidence that FHL2 is a promising target for treating arterial calcification in patients with CKD.

Project description:BackgroundChildren with type 1 diabetes have an increased risk of macrovascular complications. This study used ultra-high frequency ultrasound (UHFUS), enabling differentiation of intima thickness (IT), and media thickness (MT) in peripheral arteries, to examine early peripheral arterial changes in children with type 1 diabetes (CWD).MethodsThis cross-sectional and case-control study performed at the Queen Silvia Children's Hospital, Gothenburg, Sweden included CWD, aged 6-15.99 y/o, diabetes duration ≥5 years, compared to age and sex matched healthy controls. Exclusion criteria included other medical conditions or treatments besides insulin, abnormal examination findings or inability to handle extensive examinations. UHFUS measurements from the radial, dorsal pedal (DP), and carotid arteries as well as blood samples, blood pressure (BP)- and BMI z-score were collected from all study participants, and glucometrics from CWD.FindingsStudy inclusion was performed during 02/25/2019-06/28/2022, and a total of 50 CWD, and 41 healthy controls were included in the study. Of these, five CWD and four healthy controls were excluded, resulting in 45 (22 girls (49%), 23 boys (51%)) CWD (12.0 (2.3) y/o) and 37 (19 girls (51%), 18 boys (49%)) healthy controls (11.3 (2.5) y/o) included in data analysis. CWD had a mean HbA1c of 6.6% (48.1 mmol/mol), higher DBP z-scores (p = 0.019), DP IT, DP intima-media thickness (IMT), and radial IT compared with controls (p = 0.003, p = 0.008, and p = 0.002, respectively). Carotid IT was correlated with time in range (r = -0.47, p = 0.014), time in tight range (r = -0.64, p < 0.001), and glucose variability (r = 0.40, p = 0.004) in CWD. Time in tight range and longitudinal HbA1c were the strongest determinants for carotid IT in CWD, and type 1 diabetes diagnosis was the strongest determinant for IT across all arteries.InterpretationChildren with well-regulated type 1 diabetes show early vascular changes in radial and DP arteries. Regression analyses indicate significant links between IT and hyperglycaemia and type 1 diabetes diagnosis respectively, indicating that structural arterial changes start in the intima. Our findings further emphasise increased time in normoglycemia as the most crucial action to prevent cardiovascular complications in type 1 diabetes. Additional larger studies are needed to confirm and further interpret the meaning of these results.FundingALF-agreement, Child Diabetes Foundation, Swedish Diabetes Foundation, and the Sahlgrenska University Hospital Foundations.

Dataset Information

Intimal and medial arterial changes defined by ultra-high-frequency ultrasound: Response to changing risk factors in children with chronic kidney disease.

Background

Methods

Results

Conclusions

Publications

Intimal and medial arterial changes defined by ultra-high-frequency ultrasound: Response to changing risk factors in children with chronic kidney disease.

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