Impact of Obesity, Chronic Kidney Disease and Type 2 Diabetes on Human Urinary Stem Cells

NCT04998461 | Not Yet Recruiting

• 2 other identifiers: 69HCL21_09072021-A02135-36
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Obesity is at risk for the development of chronic kidney disease but the involved mechanisms are not known (Navarro et al. 2015). Establishing the link between obesity and kidney damage is difficult. Indeed, kidney function measurement lacks precision in obese people (Lemoine et al. 2014) and requires expensive methods such as measurement of 99mTc-DTPA clearance. Biopsies are too invasive for the detection of emerging kidney damage or for the following of the kidney function. Therefore new tools are required for the early identification of at risk individuals for the kidney damage complication. Mesenchymal stem cells may represent such a relevant tool. These cells are present in a large number of organs, including kidney (Costa et al. 2020). In addition to be differentiated cells progenitors (Dominici et al. 2006), they also support immunosuppressive, anti-fibrotic and pro-angiogenic functions that have been used for the treatment of kidney fibrosis (Usunier et al. 2014). Therefore, mesenchymal stem cells contribute to tissue homeostasis and their alterations may reflect organ dysfunctions. Indeed, mesenchymal stem cells from obese adipose tissue lose their immunosuppressive (Serena et al. 2016) and differentiation (Gustafson et al. 2009) functions and contribute to fibrosis (Keophiphath et al. 2009) and inflammation (Lee et al. 2010; Gustafson, Nerstedt, et Smith 2019). It is thus probable that kidney dysfunctions are associated with functional alterations of kidney mesenchymal stem cells. The collection of mesenchymal stem cells from kidney can easily be performed from urine and next cultivated for amplification. They are called urine stem cells (USC). From our experience with obese mouse adipose stem cells, we observed that functional changes of stem cells preceded adipose tissue dysfunctions. Functional signatures of mesenchymal stem cells are thus representative of changes occuring in the function of the tissue notably in answer to obesity. These features could be used to identify obese people presenting ongoing alterations of kidney function, before clinical manifestations of kidney dysfunction. Because kidney mesenchymal stem cells are easy to isolate from urine, their collection is compatible with the follow up of patients and can be applied to a large number of individuals, including the younger. USC could represent a valuable tool to detect progression towards kidney damage. In this project we plan to analyse USC alterations induced by obesity and to identify signatures associated with the progression towards kidney damage and type 2 diabetes. The goal is to evaluate USC as potential marker for the non invasive monitoring of patients in answer to a need that is not achieved by the present available approaches.

Conditions

Chronic Kidney Diseases; Obesity; Stem Cells; Diabetes type2

Keywords

bio-marker; Chronic Kidney Diseases; Obesity; Diabetes type2

Outcome Measures

Primary Outcomes (1)

• Comparison of gene expression in USC (Urinary Stem Cells)

  High throughput sequencing will be used to compare USC (Urinary Stem Cells) for the differential expression of genes between the 4 populations (obese or lean patients, with or without alteration of the kidney function). A gene set enrichment analysis will be used to identify the main functions supported by USC from each patient, establishing a signature.

  inclusion day

Study Arms (4)

Obese patients with normal renal function

* estimated Glomerular Filtration Rate (eDFG) ≥ 60 ml/min/1.73 m2 * Body Mass Index (BMI) \> 30 kg/m2 * Microalbuminuria / creatinuria ≤ 3mg / mmol and / or proteinuria \< 0.15 g/24h

Biological: urine collection

Obese patients with impaired renal function

* estimated Glomerular Filtration Rate (eDFG) \< 60 ml/min/1.73 m2 * Body Mass Index (BMI) \> 30 kg/m2 * Microalbuminuria / creatinuria ≤ 3mg / mmol and / or proteinuria \< 0.15 g/24h

Biological: urine collection

Non-obese patients with impaired renal function

* estimated Glomerular Filtration Rate (eDFG) \< 60 ml/min/1.73 m2 * Body Mass Index (BMI) between 18 and 30 kg/m2 * Microalbuminuria / creatinuria ≤ 3mg / mmol and / or proteinuria \< 0.15 g/24h

Biological: urine collection

Non-obese patients with normal renal function (control group)

* estimated Glomerular Filtration Rate (eDFG) ≥ 60 ml/min/1.73 m2 * Body Mass Index (BMI) between 18 and 30 kg/m2 * Microalbuminuria / creatinuria ≤ 3mg / mmol and / or proteinuria \< 0.15 g/24h

Biological: urine collection

Interventions

urine collection BIOLOGICAL

To isolate urine stem cells, a sample of 30ml minimum an 100ml maximum as a function of the patient, will be collected in a single time in a sterile flask during collection for the nephrologic exams. A transcriptome analysis of USC will be performed.

Non-obese patients with impaired renal function; Non-obese patients with normal renal function (control group); Obese patients with impaired renal function; Obese patients with normal renal function

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

This study will focus on 4 groups of non-diabetic patients, namely: 1. obese patients with preserved renal function 2. obese patients with renal failure 3. non-obese patients with preserved renal function 4. non-obese patients with renal failure (study control group)

You may qualify if:

• Age between 18 and 60
• Non diabetic (fasting blood glucose \<1.26 g/L)
• Patient not having objected to participating in the research
• eDFG ≥ 60 ml/min/1.73 m2
• BMI \> 30 kg/m2
• Microalbuminuria / creatinuria ≤ 3mg / mmol and / or proteinuria \< 0.15 g/24h
• eDFG \< 60 ml/min/1.73 m2
• BMI \> 30 kg/m2
• Microalbuminuria / creatinuria ≤ 3mg / mmol and / or proteinuria \< 0.15 g/24h
• eDFG \< 60 ml/min/1.73 m2
• BMI between 18 and 30 kg/m2
• Microalbuminuria / creatinuria ≤ 3mg / mmol and / or proteinuria \< 0.15 g/24h
• eDFG ≥ 60 ml/min/1.73 m2
• BMI between 18 and 30 kg/m2
• Microalbuminuria / creatinuria ≤ 3mg / mmol and / or proteinuria \< 0.15 g/24h

You may not qualify if:

• Acute renal failure within 3 months (defined as an increase of more than 50% in usual creatinemia)
• Inflammatory, infectious, cardiovascular or progressive neoplastic disease
• Urinary pathology (malformation, infection, etc.)

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Centre Hospitalier Lyon SUD

Pierre-Bénite, 69310, France

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Obesity

Interventions

Urine Specimen Collection

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Laetitia KOPPE, PhD

  Service de néphrologie

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laetitia KOPPE, PhD

CONTACT

04 72 67 87 15; laetitia.koppe@chu-lyon.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2021
• First Posted: August 10, 2021
• Study Start: November 1, 2021
• Primary Completion: May 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: August 10, 2021

Record last verified: 2021-08

Locations

FR (1)