Single Cell Leukocyte Landscapes and Cardiovascular Risk in Children With Chronic Kidney Disease

Study Overview
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Brief Summary
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Chronic kidney disease (CKD) is associated with an increased cardiovascular mortality. In particular children with early-onset CKD have a lifelong increased risk to suffer from cardiovascular disease (CVD). Therefore, children with CKD deserve our attention. The immune system in children with CKD is disturbed, exhibiting pro-inflammatory features. Therefore, we aim to learn more about the characteristics of the immune system in early-onset CKD. In this project PBMC of pediatric CKD patients and age-matched healthy controls will be analysed and compared using CITE-Seq as a multimodal scRNAseq phenotyping method. All patients will be clinically characterized to integrate cardiovascular and immunological data.

Official Title
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Single Cell Leukocyte Landscapes and Cardiovascular Risk in Children With Chronic Kidney Disease

Conditions
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Chronic Kidney Diseases, Cardiovascular Diseases, Microbial Colonization, Aging

Intervention / Treatment
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* Other: No intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: matching to one of the following groups CKD G3-5: estimated eGFR according to Schwartz formula <60ml/min*1,73m2 (no ESKD) CKD G5 D: patients with ESKD treated with hemodialysis for at least 3 months normal kidney function: CKD G1 or no CKD with eGFR > 90ml/min*1,73m2 informed consent to participate in this study Exclusion Criteria: body weight of less than 15kg acute or chronic inflammatory diseases fever diabetes chronic liver disease inflammatory bowel disease or other gastrointestinal disorders (constipation, diarrhea, short bowel syndrome) antibiotic prophylaxis or treatment within four weeks prior to recruitment

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CKD G3-5<br>Patients with CKD and an estimated eGFR < 60ml/min not yet on dialysis | Other: No intervention<br>* There will be no intervention in the separate goups, as this is an observational study<br>|
| End stage kidney disease (ESKD) CKD G5 Hemodialysis<br>Patients on hemodialysis for at least 3 months | Other: No intervention<br>* There will be no intervention in the separate goups, as this is an observational study<br>|
| Normal kidney function<br>Patients enrolled with normal kidney function and/or CKD G1 and an estimated eGFR > 90ml/min | Other: No intervention<br>* There will be no intervention in the separate goups, as this is an observational study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunephenotyping of human PBMC | scRNAseq with Cellular Indexing of Transcriptomes and Epitopes (CITE)-Seq for whole PBMC will be used to gain information on single cell transcriptomes across multiple immune cell populations together with expression levels of classical mmunological surface markers. | at recruitment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiome sequencing of fecal samples | 16S RNA amplicon sequencing and whole genome shotgun sequencing will be perfomred in fecal samples, collected in RNA/DNA shield. This will allow us insights in composition (abundances) and function of the gut microbiome. | at recruitment | 
| Targeted metabolomics of plasma samples | By using liquid-chromatography (LC) and gas-chromatography (GC) mass-spectrometry plasma samples will be analyzed for tryptophan metabolites and short chain fatty acids (absolute quantifiaction in µM). | at recruitment | 
| Pulse wave velocity | The pulse wave velocity (m/s) will be measured in all recruited patients by usinfg the Mobilograph. Data will be normalized to age. | at recruitment | 
| Carotid intima media thickness | The carotid intima media thickness (mm) will be measured using ultrasound imaging of the carotid vessel. Data will be normalized to age. | at recruitment | 
| Echocardiography | A basic echocardiography will be conducted evaluating diastolic and systolic, right and left ventricular function parameters. | at recruitment |