A study of genetic and environmental factors associated with kidney disease in people of African ancestry living in the UK
| ISRCTN | ISRCTN17433656 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN17433656 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Integrated Research Application System (IRAS) | 292365 |
| Protocol serial number | IRAS 292365, CPMS 52421 |
| Sponsors | King's College Hospital NHS Foundation Trust, King's College London |
| Funder | AstraZeneca |
- Submission date
- 04/05/2022
- Registration date
- 05/05/2022
- Last edited
- 16/04/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Urological and Genital Diseases
Plain English summary of protocol
Background and study aims
People of African or Afro-Caribbean ancestry are five times more likely to have kidney disease. They also develop kidney failure when they are about 10 years younger than white people. The connection between ethnicity and kidney disease is complex.
A gene pattern (APOL1-G1/G2 alleles) has been found which is common in people of African and Afro-Caribbean ancestry. We think this gene pattern prevents some forms of sleeping sickness which is why so many people of West African and Afro-Caribbean ancestry have these gene patterns. This gene pattern may make it more likely for some people to develop kidney disease (including particular types of disease: focal segmental glomerulosclerosis (FSGS), hypertensive-associated kidney disease). We do not completely understand why some people with these gene patterns develop kidney disease while others do not. We think there are additional factors including extra genetic changes and/or environmental triggers e.g. infection which lead to onset of kidney disease.
We would like to test your blood, urine and kidney tissue (if you have previously had a kidney biopsy) to get more information. This will allow us to develop tests to predict who is going to have kidney damage and find ways to prevent damage. You do not need to have a kidney biopsy if you have not already had one as part of your clinical care.
Who can participate?
For CKD Group:
You are of African or Afro-Caribbean ancestry and have kidney disease. This means that either your kidneys work less well than expected or that your kidneys leak protein or blood into your urine.
For Control Group:
You are of African or Afro-Caribbean ancestry and DO NOT have kidney disease
What does the study involve?
You will see one of the doctors or nurses who will answer any questions that you may have. If you agree to take part, we will ask you to sign a consent form and you will be given a copy to keep. We will then take extra blood, and urine from you. We will take a minimum of one extra blood test from you and we will try to do these tests when you attend your normal appointments so you will not have any extra visits to the hospital or extra needles. We will take no more than 40 ml of blood from you at one point (4 tablespoons). There will be no repeat blood tests after this. We will also look at relevant medical records.
If you have had a kidney biopsy we will ask for your permission to retrieve any spare tissue that is available from storage for testing. You will not be asked to have any more kidney biopsy samples taken.
What are the possible benefits and risks of participating?
Your samples and information may help us to improve the treatment of people of African or Afro-Caribbean ancestry with kidney disease in the future.
There are no risks to you by taking part. The amount of extra blood that we take will not affect you. Occasionally people experience pain or bruising from having blood taken, but we will try to do this at the same time as your routine blood tests to minimise discomfort.
Where is the study run from?
The study will be running in the Renal Unit of King's College Hospital NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
March 2022 to November 2024
Who is funding the study?
The study is co-sponsored by King’s College Hospital NHS Foundation Trust and Kings College London and funded by AstraZeneca (UK).
Who is the main contact?
1. Dr Kate Bramham, kate.bramham@kcl.ac.uk
2. Amrita Ramnarine, amrita.ramnarine@kcl.ac.uk
3. Dalvir Kular, dalvir.kular@kcl.ac.uk
Contact information
Principal investigator
King's College Hospital NHS Foundation Trust
Renal Unit
Denmark Hill
London
SE5 9RS
United Kingdom
 ORCID ID |
0000-0002-6272-7921 |
|---|---|
| Phone | +44 203 299 6233 |
| kate.bramham@kcl.ac.uk |
Study information
| Primary study design | Observational |
|---|---|
| Study design | Multicentre observational cohort |
| Secondary study design | Cohort study |
| Participant information sheet | 41696 APPLE CKD PIS Case V1.1 25Apr2022.pdf |
| Scientific title | APolipoprotein L1 in People of African ancestry Living in the UK: Exploration of genetic and environmental factors associated with Chronic Kidney Disease (APPLE-CKD) |
| Study acronym | APPLE-CKD |
| Study objectives | Primary: To establish if epigenetic DNA methylation patterns in the APOL1 gene promoter in renal tissue are comparable to peripheral blood mononuclear cells PBMC (or spleen) and urine in participants with CKD and controls (including deceased kidney donors) with APOL1 high and low-risk genotypes Secondary: 1. To study the role of APOL1 genetics and epigenetics in the differentiation of inducible Pluripotent Stem Cells into kidney relevant cells 2. To develop a ‘clinical/genetic/epigenetic/inflammatory signature’ associated with CKD in people of African ancestry with validation |
| Ethics approval(s) | Approved 03/05/2022, North West - Greater Manchester West Research Ethics Committee (Barlow House, 3rd Floor, 4 Minshull Street, Manchester, M1 3DZ, UK; +44 2071048007; gmwest.rec@hra.nhs.uk), ref 22/NW/0100 |
| Health condition(s) or problem(s) studied | Exploration of genetic and environmental factors associated with chronic kidney disease in patients of African ancestry |
| Intervention | In the study, plasma, serum, urine, pre-existing renal tissue and peripheral blood mononuclear cells (PBMC) will be collected from patients. These will be sent for further analyses for: 1. Genotyping and epigenetic analysis - for PBMC (spleen MCs), renal biopsy tissue, urine pellets cases and controls 2. APOL1 and inflammatory marker analysis - for plasma, serum, renal biopsy tissue, urine supernatant and urine pellets 3. Inducible Pluripotent Stem Cell (iPSC) analysis - for the cryopreserved PBMCs |
| Intervention type | Genetic |
| Primary outcome measure(s) |
At a single time point: |
| Key secondary outcome measure(s) |
At a single time point: |
| Completion date | 30/11/2024 |
Eligibility
| Participant type(s) | Healthy volunteer, Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | All |
| Target sample size at registration | 240 |
| Key inclusion criteria | CKD cases: 1. Self-reported African ancestry 2. Aged ≥18 years 3. Willing and able to provide written informed consent 4. Chronic kidney disease (KDIGO Criteria) 5. Group 1: Without diabetic nephropathy or serological or biopsy-proven evidence of immune-mediated kidney disease 6. Group 2: With diabetic nephropathy or serological or biopsy-proven evidence of immune-mediated kidney disease Controls: 1. Self-reported African ancestry 2. Aged ≥18 years 3. Willing and able to provide written informed consent 4. No CKD (estimated GFR >60 ml/min/1.73m² and urinary protein: creatinine <15mg /mol or albumin: creatinine ratio <3 mg/mmol or negative urine dip for protein). |
| Key exclusion criteria | For both CKD cases and controls: 1. Unable to provide informed consent 2. Pregnancy |
| Date of first enrolment | 01/06/2022 |
| Date of final enrolment | 01/11/2024 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centres
London
SE5 9RS
United Kingdom
Great Maze Pond
London
SE1 9RT
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 20/09/2023 | No | No | ||
| Participant information sheet | Cases version 1.1 |
25/04/2022 | 05/05/2022 | No | Yes |
| Participant information sheet | Controls version 1.1 |
25/04/2022 | 05/05/2022 | No | Yes |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Protocol file | version 1.1 | 25/04/2022 | 05/05/2022 | No | No |
Additional files
- 41696 Protocol V1.1 25Apr2022.pdf
- Protocol file
- 41696 APPLE CKD PIS Control V1.1 25Apr2022.pdf
- Controls
- 41696 APPLE CKD PIS Case V1.1 25Apr2022.pdf
- Cases
Editorial Notes
16/04/2025: Royal London Hospital and Associated Community Services NHS Trust was removed as a study participating centre.
10/10/2024: Guys Hospital and Royal London Hospital and Associated Community Services NHS Trust were added to the study participating centres.
20/09/2023: A link to the HRA research summary was added.
07/06/2022: Internal review.
05/05/2022: Trial's existence confirmed by North West - Greater Manchester West Research Ethics Committee.
